United States Prevention, Pesticides EPA738-R-07-012
Environmental Protection And Toxic Substances September 2007
Agency (7508P)
Reregistration
Eligibility Decision
Flumetralin
ListD
Case No. 4119
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Reregistration Eligibility Decision (RED) Document
for Flumetralin
Approved by:
Steven Bradbury, Ph. D.
Director,
Special Review and Reregistration Division
Date: 09/28/2007
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Table of Contents
Summary 7
I. Introduction 9
II. Chemical Overview 9
A. Regulatory History 9
B. Chemical Identification 9
C. Flumetralin Use Profile 11
D. Estimated Usage 11
III. Summary of Flumetralin Risk Assessments 12
A. Human Health Risk Assessment 12
1. Toxicity of Flumetralin 12
2. Endpoint Selection 14
3. Dietary Exposure and Risk (Drinking Water Only) 16
4. Residential (Non-Occupational) Exposure and Risk 17
5. Aggregate Exposure and Risk 18
6. Occupational Exposure and Risk 18
7. Endocrine Disruption 20
8. Incident Reports 20
B. Environmental Risk Assessment 20
1. Environmental Fate and Transport 20
2. Ecological Exposure and Risk 21
IV. Risk Management and Reregistration Decision 28
A. Human Health Risks 28
B. Ecological Risks 28
V. What Registrants Need to Do 29
A. Manufacturing Use Products 29
1. Additional Generic Data Requirements 29
2. Labeling for Technical and Manufacturing Use Products 30
B. End-Use Products 30
1. Additional Product-Specific Data Requirements 30
2. Labeling for End-Use Products 30
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Flumetralin Reregistration Eligibility Decision Team
Office of Pesticide Programs:
Health Effects Division
Matt Lloyd
Chris Olinger
Linda Taylor, Ph.D.
Environmental Fate and Effects Division
Brian Kiernan
Cheryl A. Sutton, Ph.D.
Registration Division
Tony Kish
Biological and Economic Analysis Division
Alan Halvorson
Sunil Ratnayake
Elisa Rim
Special Review and Reregistration Division
Katherine St. Clair
Tom Myers
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Glossary of Terms and Abbreviations
ai
CFR
CSF
DCI
EC
EEC
EPA
EUP
FDA
FIFRA
FFDCA
FQPA
G
GLN
LOC
LOD
LOAEL
mg/kg/day
mg/L
MOE
MRID
MUP
NA
NPDES
NR
NOAEL
OPP
OPPTS
PHED
PHI
ppb
PPE
ppm
RED
REI
RfD
RQ
SAP
SF
SLC
SLN
Active Ingredient
Code of Federal Regulations
Confidential Statement of Formula
Data Call-In
Emulsifiable Concentrate Formulation
Estimated Environmental Concentration
Environmental Protection Agency
End-Use Product
Food and Drug Administration
Federal Insecticide, Fungicide, and Rodenticide Act
Federal Food, Drug, and Cosmetic Act
Food Quality Protection Act
Granular Formulation
Guideline Number
Level of Concern
Limit of Detection
Lowest Observed Adverse Effect Level
Micrograms Per Gram
Micrograms Per Liter
Milligram Per Kilogram Per Day
Milligrams Per Liter
Margin of Exposure
Master Record Identification (number). EPA's system of recording
and tracking studies submitted.
Manufacturing-Use Product
Not Applicable
National Pollutant Discharge Elimination System
Not Required
No Observed Adverse Effect Level
EPA Office of Pesticide Programs
EPA Office of Prevention, Pesticides and Toxic Substances
Pesticide Handler's Exposure Data
Preharvest Interval
Parts Per Billion
Personal Protective Equipment
Parts Per Million
Reregi strati on Eligibility Decision
Restricted Entry Interval
Reference Dose
Risk Quotient
Science Advisory Panel
Safety Factor
Single Layer Clothing
Special Local Need (Registrations Under Section 24(c) of FIFRA)
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TGAI Technical Grade Active Ingredient
USDA United States Department of Agriculture
USGS United States Geological Survey
UF Uncertainty Factor
UV Ultraviolet
WPS Worker Protection Standard
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Summary
The Environmental Protection Agency (hereafter referred to as "EPA" or "the
Agency") has evaluated the risks from the supported uses of flumetralin and has
determined that no unreasonable adverse effects will result from exposure to registered
flumetralin products. The Agency has determined that the products containing
flumetralin are eligible for reregi strati on provided the risk mitigation measures outlined
in this document are adopted and label amendments are made.
Flumetralin is a plant growth regulator that is used to control axillary bud (sucker)
growth on tobacco plants. Flumetralin was first registered for use in 1983, and can be
applied using hand or ground spray equipment. The current average total annual
domestic usage of flumetralin is approximately 60,000 pounds active ingredient (a.i.).
There are no registered food or feed uses for flumetralin. There are no registered
residential uses for flumetralin.
The Agency conducted a human health risk assessment to address potential exposure
risks from all registered sources. There are no registered food or feed uses for flumetralin
and thus no food-related dietary risk assessments were conducted. However, since
flumetralin products are used outdoors on tobacco crops, there is potential for flumetralin
to move to drinking water sources. Thus, a dietary risk assessment was conducted for
acute and intermediate-term drinking water exposures only. Acute and intermediate-term
risk estimates are below the Agency's level of concern. There are no residential uses for
flumetralin. However, residential exposure to flumetralin can occur through the use of
tobacco products (i.e., smoking). Since no acute hazard was identified for the tobacco
smoking scenario, a residential risk assessment was not needed. Exposure through
drinking water is the only exposure route and an aggregate risk assessment for
flumetralin was not needed.
The Agency conducted a risk assessment on the occupational uses of flumetralin,
including handlers that mix, load, and apply flumetralin in various ways. All
occupational handler scenarios assessed for flumetralin have Margins of Exposure
(MOEs) above 100 and therefore risk estimates are below the Agency's level of concern.
Occupational post-application dermal exposures were not evaluated because there is no
dermal hazard for flumetralin from short-term exposure durations. Intermediate- and
long-term exposure durations are unlikely due to the current use pattern of one
application per season. Potential inhalation exposures are not anticipated for the post-
application worker scenarios because of the low vapor pressure of flumetralin.
An ecological effects risk assessment was also conducted for flumetralin. Based on
the most sensitive endpoint for each of the taxa evaluated, only RQs for chronic exposure
to mammals and acute exposure to terrestrial plants are exceeded. The RQ values for
acute effects to listed freshwater fish and chronic effects to mammals and for non-target
terrestrial plants exceed the Agency's level of concern for flumetralin. No data are
available to assess risk to aquatic nonvascular plants and chronic risk to birds.
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No human health risks of concern were identified for flumetralin. The current REI on
flumetralin labels is 24 hours. However, based on the toxicity category III assigned to
the most recent acceptable primary eye irritation studies, the REI on flumetralin labels
may be decreased to 12 hours. Due to a residue chemistry data deficiency, all product
labels must be modified to establish a 10-month plantback interval for all crops. If the
registrant wants to establish a plantback interval shorter than 10 months, a confined
rotational crop study with flumetralin must be conducted.
Due to the high persistence of flumetralin in the environment and to reduce potential
exposure to flumetralin, the labeling statements shown in Table 8, the Labeling Changes
Summary Table, must be added to the flumetralin labels.
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I. Introduction
The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended in
1988 to accelerate the reregi strati on of products with active ingredients registered prior to
November 1, 1984, and amended again by the Food Quality Protection Act of 1996
(FQPA) and the Pesticide Registration Improvement Act of 2003 (PRIA) to set time
frames for the issuance of Reregistration Eligibility Decisions (RED). FIFRA calls for
the development and submission of data to support the reregi strati on of an active
ingredient, as well as a review of all data submitted to the U.S. Environmental Protection
Agency. Reregi strati on involves a thorough review of the scientific database underlying
a pesticide's registration. The purpose of the Agency's review is to reassess the potential
risks arising from the currently registered uses of a pesticide, to determine the need for
additional data on health and environmental effects, and to determine whether or not the
pesticide meets the "no unreasonable adverse effects" criteria of FIFRA.
This document presents the EPA's decision regarding the reregi strati on eligibility of
all currently registered uses of flumetralin. The Agency made its reregi strati on eligibility
determination based on the required data, the current guidelines for conducting
acceptable studies to generate such data, and published scientific literature. The Agency
has found that current registered uses of flumetralin are eligible for reregi strati on
provided the mitigation and labeling outlined in this RED are implemented. The revised
risk assessment documents and related addenda are not included in this document, but are
available on the Agency's web page, http://www.epa.gov/pesticides/registration/status,
and in the Public Docket under docket number EPA-HQ-OPP-2007-0990.
II. Chemical Overview
A. Regulatory History
There is only one active ingredient in reregi strati on case 4119 for flumetralin. Only
active product registrations containing this active ingredient were evaluated for this RED.
Flumetralin has been registered since 1983 for use only on tobacco. Currently, there
are six active registrations in this case. Registrations are held by Syngenta Crop
Protection, Inc., Drexel Chemical Co., and SRM Chemical LTD. Co. Each of the three
registrants has one technical and one end-use product registration.
B. Chemical Identification
Flumetralin is registered as a plant growth regulator. It is a member of the 2,6-
dinitroaniline class of chemicals. The chemical structure and properties of flumetralin
are presented in Table 1 and Table 2.
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Table 1: Flumetralin Nomenclature
Chemical structure
Common name
Molecular formula
Molecular weight
PC Code
IUPAC name
CAS name
CAS registry number
Cl^^
02NX
^'
N CH3
9-
CF3
Flumetralin
C16H12C1F4N304
421.74 mol
123001
N-(2-chloro-6-fluorobenzyl)-N-ethyl-2,6-dinitro-4-(trifluoromethyl)aniline
2-chloro-N-[2,6-dinitro-4-(trifluoromethyl)phenyl]-N-ethyl-6-
fluorobenzenemethanamine
62924-70-3
Table 2: Physicochemical Properties of Flumetralin
Parameter
Melting point/range
pH
Density
Water solubility
Solvent solubility
Vapor pressure
Dissociation constant, pKa
Octanol/water partition coefficient,
Log(Kow)
UV/visible absorption spectrum
Value
101-103 °C
Not available
Not available
0.07 ppm at 20 °C
Not available
0.032 mPa at 25 °C
Not available
5. 45 at 25 °C
Not available
Reference
Agrochemicals Handbook J
-
-
Pesticide Manual 2
-
Pesticide Manual 2
-
Pesticide Manual 2
-
Agrochemicals Handbook, 2nd Edition, RSC, Nottingham, UK 1987
(www.arsusda.gov/acsl/services/ppdb).
2 Pesticide Manual, 10th Ed., British Crop Protection Council, and The Royal Society Of Chemistry, 1994
(www.arsusda.gov/acsl/services/ppdb).
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C. Flumetralin Use Profile
Type of Pesticide: Plant growth regulator.
Summary of Use: Flumetralin is a plant growth regulator used on tobacco for control
of axillary bud (sucker) growth. It is used for control of suckers on
flue-cured, burley, Maryland, and cigar tobacco plants.
Flumetralin is absorbed by the tobacco plant within a few hours
after application and provides residual sucker control through the
growing season.
Mode of Action: Flumetralin is in the 2,6-dinitroaniline class of chemicals.
Dinitroanilines selectively inhibit the microtubules of plants and
protozoa and do not act on fungal or vertebrate tubulins.
Formulation Type: Emulsifiable concentrate.
Application Methods: Flumetralin is applied as a hand spray or ground spray.
Application Rates: The currently labeled maximum application rate is 1.2 pounds of
active ingredient per acre (Ibs. ai/A). Current labels specify a re-
entry interval (REI) of 24 hours.
Application Timing: Flumetralin is applied only once per growing season. It is typically
applied between 3 and 7 days after the floral portion of tobacco
plants have been topped.
Registrants: Syngenta Crop Protection, Inc.; Drexel Chemical Co.; SRM
Chemical LTD. Co.
D. Estimated Usage
Based on Agency data, the current average total annual domestic usage of flumetralin
is approximately 60,000 pounds active ingredient (a.i.) and the current maximum percent
crop treated is 25 percent. Flumetralin is not registered for any other use other than as a
plant growth regulator on tobacco.
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III. Summary of Flumetralin Risk Assessments
The purpose of this summary is to assist the reader by identifying the key features and
findings of the human health and environmental risk assessments, and to help the reader
better understand the conclusions reached in the assessments. These assessments and
supporting documents referenced in Appendix C were used to formulate the safety
finding and regulatory decision for the pesticidal use of flumetralin.
While the risk assessments and related addenda are not included in this document,
they are available in the OPP Public Docket, docket number EPA-HQ-OPP-2007-0990,
and may be accessed through the Agency's website at Mtpj//www,regulMiQns.goy/. Hard
copies of these documents may also be found in the OPP Public Docket under this same
docket number.
• Flumetralin: Revised HED Chapter of the Reregistration Eligibility Decision
Document (RED) (M. Lloyd, et. al.; 6/21/07, D326449).
• Environmental Fate and Ecological Risk Assessment in Support of the
Reregistration Eligibility Decision for Flumetralin (Kiernan, B. and Sutton,
C., Ph.D.; 7/10/07, D326441).
A. Human Health Risk Assessment
Flumetralin is registered to be applied only to commercial tobacco crops, and it is
considered to be a "non-food use" chemical. The human health risk assessment addresses
potential exposure risks from all registered sources. Flumetralin exposure to handlers can
occur in occupational environments. There are no registered food or feed uses for
flumetralin and thus no food-related dietary risk assessments were conducted. However,
since flumetralin products are used outdoors on tobacco crops, there is potential for
flumetralin to move to drinking water sources. Thus, the risk assessment also considered
drinking water exposures. There are no residential uses. Non-occupational exposure to
flumetralin can occur through the use of tobacco products (i.e., cigarette smoking). For
the complete human health risk assessment, refer to Flumetralin: Revised HED Chapter
of the Reregistration Eligibility Decision Document (RED), dated June 21, 2007, which is
available in the public docket.
1. Toxicity of Flumetralin
The human health risk assessment utilized animal toxicity studies to estimate risk to
humans exposed to flumetralin. The toxicological database on flumetralin is considered
complete and the available data are sufficient for selecting endpoints for risk assessment.
Flumetralin has a low acute toxicity profile (Toxicity Category III or IV). It is a mild
dermal irritant and is a positive dermal sensitizer. A new dermal sensitization study was
submitted, but determined to be unacceptable. Table 3 describes the acute toxicity profile
of flumetralin.
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Table 3: Flumetralin Acute Toxicity Profile
Guideline No.
870.1100
870.1200
870.1300
870.2400
870.2500
870.2600
Study Type
Acute oral [rat]
Acute dermal [rat]
Acute inhalation [rat]
Primary eye irritation [rabbit]
Acute dermal irritation [rabbit]
Skin sensitization [guinea pig]
MRID(s)
471877-01
471877-02
471877-03
471877-04
471877-06
00094001
Results
LD50 > 2000
mg/kg
LD50 = >2000
mg/kg
LC50 = >2.22
mg/L
mildly irritating
mild irritant
positive skin
sensitizer
Toxicity Category
III
III
IV
III
III
N/A
Subchronic Studies
No systemic toxicity was observed in the 21-day rabbit dermal toxicity study at the
limit dose. Dermal irritation was observed at all dose levels (500 mg/kg/day and above).
No effects were reported in a rat 6-week smoking inhalation study (inhalation of smoke
from cigarettes made of tobacco treated with flumetralin).
In the subchronic oral toxicity study in dogs, clinical signs of toxicity (weight loss,
decreased food consumption, fever, dehydration, depression), which were progressive
over a period of two to four weeks, occurred in both sexes at the high-dose level, with
two dogs of each sex dying during the test (on days 40, 128). One male dog at the mid-
dose level also died during the test following longer exposure (day 169).
Developmental Studies
The developmental and reproduction toxicity studies did not indicate an enhanced
sensitivity or susceptibility to the young. Developmental/offspring effects occurred at
doses higher than or equal to doses eliciting parental toxicity and were of comparable
severity.
Developmental toxicity was observed in the rabbit, as evidenced by the increased
incidence of litters with total resorption, increased post-implantation loss, increased
incidence of external (flexure of forepaw at the wrist) and skeletal alterations (fused
sternebrae and absent ossification of the caudal vertebral centers) at 100 and 200
mg/kg/day. In the rat, there was a slight increase in external and skeletal malformations
at 400 mg/kg/day. Maternal toxicity occurred at the same doses as developmental
toxicity in both species.
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Reproductive toxicity was not observed in the rat following exposure to flumetralin.
Decreased body weight was observed in the offspring at the high-dose level. In the
maternal animal, a slight decrease in body weight was observed during the dosing period
and throughout gestation and lactation at both the mid- and high-dose levels (i.e.,
maternal toxicity was observed at a lower dose than developmental toxicity).
Carcinogenicity and Mutagenicity Studies
In the combined rat oral chronic toxicity/carcinogenicity study, there were no clinical
signs of toxicity and no adverse effects on survival. Decreased body weight and body-
weight gain were observed in both sexes throughout the study, but there were no
consistent effects on food consumption. Increased liver weight and increased incidence
of blood and kidney changes were observed.
In the mouse carcinogenicity study, there were no clinical signs of toxicity, and no
adverse effects on survival, body weight/gain, food consumption, or hematology
parameters. There was an increase in liver weight in both sexes at the two highest dose
levels.
Flumetralin did not produce a tumorigenic response in either the rat or mouse
carcinogenicity studies. The mutagenicity database is adequate and no mutagenicity was
observed in the mutagenicity studies conducted with flumetralin.
Neurotoxicity Studies
There is no acute neurotoxicity study on flumetralin available. No clinical signs
indicating neurotoxicity were observed in the chronic toxicity/carcinogenicity study in
rats, the developmental toxicity studies in rats and rabbits, the carcinogenicity study in
mice, or the 21-day dermal toxicity study in rabbits at the limit dose and twice the limit
dose. The decreased motor activity and piloerection in the maternal rabbits that displayed
total litter resorption are considered to be the result of high dose toxicity and not a
neurotoxic effect.
2. Endpoint Selection
Table 4 summarizes the toxicological doses and endpoints used in the human health
risk assessment of flumetralin.
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Table 4: Toxicological Doses and Endpoints for Flumetralin for Use in Human Health Risk
Assessments
Exposure/
Scenario
Point of
Departure
Uncertainty
Factors
RfD/Level
of Concern
for Risk
Assessment
Study and Toxicological Effects
Acute Dietary
- Drinking
Water Only
(Females
13+)
NOAEL=
50
mg/kg/day
UFA= lOx
UFH= 10x
aRfD = 0.5
mg/kg/day
Developmental Toxicity - Rabbit
LOAEL =100 mg/kg/day; an increased
incidence of litters with total resorptions,
increased post-implantation loss, and
increased incidence of external
(positional anomaly) and skeletal (fused
sternebrae and absent ossification of the
caudal vertebral centers) alterations.
Acute Dietary
- Drinking
Water Only
(General
population
including
infants and
children)
Based upon available data, no toxicity is expected to the general population resulting from
a single day exposure to flumetralin.
Intermediate-
Term Dietary
- Drinking
Water Only
(All
Populations)
NOAEL=
11.6
mg/kg/day
UFA= lOx
UFH= lOx
LOC =
MOE< 100
Subchronic Oral Toxicity - Dog
LOAEL = 92.75 mg/kg/day for clinical
signs (weight loss, decreased food
consumption, pyrexia, dehydration, and
depression), mortality, hematology/
clinical chemistry effects
Chronic
Dietary -
Drinking
Water Only
(All
populations)
Chronic drinking water exposures are not expected, so a chronic dietary endpoint was not
selected.
Short-
/Intermediate-
Term
Incidental
Oral
There are no registered residential uses of flumetralin, thus no exposure is expected.
Dermal
Short -
Intermediate-
/Long-term
No dermal exposure is expected for this scenario based on current use patterns and no
hazard was identified in the route-specific study.
Acute
Inhalation
(smoking
assessment)
No hazard was identified in the route-specific (smoking inhalation) study.
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Table 4: Toxicological Doses and Endpoints for Flumetralin for Use in Human Health Risk
Assessments
Exposure/
Scenario
Short-Term
Inhalation (1
to 30 days)
Intermediate-
/Long-Term
Inhalation
Cancer (oral,
dermal,
inhalation)
Point of
Departure
oral
NOAEL=
11.6
mg/kg/day
toxicity via
inhalation
route
considered to
be equivalent
to toxicity via
oral route
Uncertainty
Factors
UFA= lOx
UFH= 10x
RfD/Level
of Concern
for Risk
Assessment
LOC =
MOE< 100
Study and Toxicological Effects
Subchronic Oral Toxicity - Dog
LOAEL = 92.75 mg/kg/day for clinical
signs (weight loss, decreased food
consumption, pyrexia, dehydration, and
depression), mortality, hematology/
clinical chemistry effects
No inhalation exposure is expected for this exposure duration based on current use
patterns.
A cancer risk assessment was not conducted since flumetralin did not produce a
tumorigenic response in either the rat or mouse carcinogenicity study and mutagenicity
was not observed in the battery of studies performed on flumetralin.
Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response
data and used to mark the beginning of extrapolation to determine risk associated with lower
environmentally relevant human exposures. UF = uncertainty factor, UFA = extrapolation from animal to
human (interspecies). UFH = potential variation in sensitivity among members of the human population
(intraspecies), NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level,
MOE = margin of exposure, LOG = level of concern, RfD = Reference Dose
3. Dietary Exposure and Risk (Drinking Water Only)
There are no registered food or feed uses for flumetralin; therefore, a food-related
dietary risk assessment is not needed and has not been conducted. However, since
flumetralin products are used outdoors on tobacco crops, there is a possibility for
exposure to flumetralin through drinking water. Considering the use pattern and
environmental fate characteristics of flumetralin, the most likely durations for exposure to
flumetralin from drinking water (surface water sources) are acute (one-day) and
intermediate-term (1-6 months). Ground water estimates were much lower than the
estimates from surface water sources, so surface water estimates were used in the
drinking water assessment and are protective of all drinking water exposures.
Typically, the Agency uses the reference dose approach for estimating risk from acute
and chronic dietary exposures only. Therefore, the Margin of Exposure (MOE) approach
was used to assess the risk from the intermediate-term drinking water exposures from
flumetralin.
Both approaches incorporate the exposure and toxicity of a pesticide. For acute
assessments, the risk is expressed as a percentage of a maximum acceptable dose (i.e., the
dose which the Agency has concluded will result in no unreasonable adverse health
effects). This dose is referred to as the reference dose (RfD). The RfD is equivalent to
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point of departure (POD), in this case aNOAEL, divided by the appropriate uncertainty
factors.
For intermediate-term exposures the risk is expressed as a Margin of Exposure
(MOE), which is determined by dividing the point of departure by the estimated
exposure. The MOE is typically compared to the level of concern (LOG), usually the
product of all of the appropriate uncertainty factors, in this case 100.
For acute exposure assessments, individual one-day water consumption data are used
on an individual-by-individual basis. The reported consumption amounts can be
multiplied by a residue point estimate and summed to obtain a total daily pesticide
exposure for a deterministic exposure assessment, or "matched" in multiple random
pairings with residue values and then summed in a probabilistic assessment. The
resulting distribution of exposures is expressed as a percentage of the aRfD.
For intermediate-term dietary exposure assessment, an estimate of the residue level in
water is multiplied by the average daily consumption estimate for water to produce a
residue intake estimate. The resulting residue intake estimates for indirect and direct
sources of water are summed to arrive at the total average estimated exposure. The
exposure is expressed in mg/kg body weight/day and is divided by the point of departure
for intermediate-term exposures to obtain the margin of exposure (MOE). This
procedure is performed for each population subgroup.
The endpoints used in the drinking water assessment are outlined in Table 4.
Acute Drinking Water Only Risk
No hazard was identified for the general population, so an acute assessment was
conducted for females aged 13-49, the subpopulation of concern. The acute exposure to
flumetralin results in an estimated risk that is <1% of the acute reference dose, and is not
of concern.
Intermediate-Term Drinking Water Only Risk
The results of the intermediate-term dietary exposure analysis indicate that the
margins of exposure (MOE) for all population groups are greater than 100, the level of
concern for this assessment, and therefore are not of concern. The most-highly exposed
subgroup is infants less than 1 year old (MOE = 19100).
4. Residential (Non-Occupational) Exposure and Risk
Flumetralin is a plant growth regulator for use only on tobacco in occupational
settings, and there are no residential uses of flumetralin. Non-occupational inhalation
exposure to flumetralin can occur through the use of tobacco products (e.g. cigarette
smoking).
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For the acute (smoker) inhalation assessment, the NOAEL endpoint from a 6-week
smoking study in rats (inhalation of smoke from cigarettes made of tobacco treated with
flumetralin) was considered because the route of exposure is appropriate. No systemic
toxicity was observed in the 6 week study at rates much higher than would be expected
under normal use conditions. This study is most representative of the residential
(smoking) exposure to flumetralin. Since no hazard was identified from the 6 week
smoking study, a quantitative residential inhalation assessment is not needed.
The current use pattern and registered uses for flumetralin do not indicate
intermediate- or long-term occupational/residential exposure durations. Consequently,
intermediate- and long-term risk assessments via the inhalation route were not conducted.
5. Aggregate Exposure and Risk
The Agency has not conducted a quantitative or qualitative aggregate assessment for
flumetralin. An aggregate exposure assessment considers the different pathways (food,
water, occupational, and residential) through which exposure to flumetralin may occur.
There are no food exposures to flumetralin, and while residential exposure to flumetralin
can occur through the use of tobacco products (i.e., cigarette smoking), no acute hazard
was identified in the relevant toxicological studies for a 'smoking' assessment and thus
no quantification of risk is required for that exposure scenario. Therefore, exposure
through drinking water is the only exposure route possible and an aggregate risk
assessment for flumetralin is not needed.
6. Occupational Exposure and Risk
a) Occupational Handler/Application Assessment
Based on current use patterns, flumetralin exposure to occupational handlers can
occur. The representative scenarios selected by the Agency for assessment were
evaluated using maximum product label rates (i.e., 1.2 Ibs ai/A for all occupational
scenarios).
To assess the handler risks, the Agency used surrogate unit exposure data from the
Pesticide Handlers Exposure Database (PHED). Only short-term (1-30 days) inhalation
risks were evaluated because no dermal toxicity was observed in existing studies.
For the short-term inhalation exposure scenario for workers, the endpoint from a 6-
month oral toxicity study in dogs was selected based on clinical signs of toxicity which
were progressive over the first two to four weeks of exposure prior to death (2 males, one
female) on day 40. Based on the current use pattern and registered uses for flumetralin,
the EPA does not expect intermediate- or long-term occupational/residential exposures.
Consequently, intermediate- and long-term risk assessments via the inhalation route were
not conducted.
Endpoints selected for the occupational handler assessment are outlined in Table 4.
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All occupational handler scenarios have Margins of Exposure (MOEs) above 100 and
therefore risk estimates are below the Agency's level of concern. Table 5 presents the
MOEs for occupational handler inhalation exposure to flumetralin.
Table 5: Flumetralin Short-term Inhalation MOEs for Agricultural Handlers
Exposure Scenario
Typical Crops
Ib ai/acre
Acres per Day
MOEwith
Base-
Line PPE1
Mixer/Loader (M/L): (1.2 ug/lb ai inhalation unit exposure)
M/L Liquids for Groundboom
application
tobacco
1.2
80
7,000
Applicator (APP): (0.74 ug/lb ai inhalation unit exposure)
Groundboom Application
tobacco
1.2
80
11,000
Mixer/Loader/Applicator (M/L/A): (30 ug/lb ai inhalation unit exposure)
M/L/ A Liquids with LP
Handwand
M/L/A Liquids with Backpack
Sprayer
tobacco
tobacco
1.2
1.2
1
1
23,000
23,000
*A11 MOEs are greater than 100 and are therefore below EPA's level of concern (MOEs > 100).
1 - Baseline PPE = shoes + socks, long-sleeve shirt, long pants
b) Occupational Post-application Exposures
Occupational post-application dermal exposures were not evaluated because there is
no dermal hazard for flumetralin from short-term exposure durations. Intermediate- and
long-term exposure durations are unlikely due to the current use pattern of one
application per season. Potential inhalation exposures are not anticipated for the
postapplication worker scenarios because of the low vapor pressure of flumetralin (0.032
mPa at 25 °C).
For uses within the scope of the Worker Protection Standard for Agricultural
Pesticides (40 CFR 170), a restricted entry interval (REI) is established to minimize
exposure to workers that may pose risks of concern. The REI is based on the category
assigned to the acute dermal toxicity, skin irritation potential, and eye irritation potential
of the active ingredient. The current REI for flumetralin is 24 hours. Based on the
Toxicity Category III assigned to the most recent acceptable primary eye irritation
studies, the REI on flumetralin labels may be decreased to 12 hours.
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7. Endocrine Disruption
EPA is required under the FFDCA, as amended by FQPA, to develop a screening
program to determine whether certain substances (including all pesticide active and other
ingredients) "may have an effect in humans that is similar to an effect produced by a
naturally occurring estrogen, or other such endocrine effects as the Administrator may
designate. " Following the recommendations of its Endocrine Disrupter Screening and
Testing Advisory Committee (EDSTAC), EPA determined that there were scientific
bases for including, as part of the program, androgen and thyroid hormone systems, in
addition to the estrogen hormone system. EPA also adopted EDSTAC's recommendation
that the Program include evaluations of potential effects in wildlife. When the
appropriate screening and/or testing protocols being considered under the Agency's
Endocrine Disrupter Screening Program (EDSP) have been developed and vetted,
flumetralin may be subjected to additional screening and/or testing to better characterize
effects related to endocrine disruption.
8. Incident Reports
There are 16 incidents involving flumetralin in OPP's Incident Data System (IDS); no
other system identified any incident reports involving flumetralin. Most were of mild to
moderate severity and involved nausea and vomiting; six incidents involved localized
skin irritation (typically a rash) that is consistent with toxicological data suggesting
flumetralin is a dermal sensitizer. It is unclear from the available incident data whether
proper protective clothing, as required by the label, was worn or whether hospitalization
occurred after any of the flumetralin exposures.
B. Environmental Risk Assessment
The Agency conducted an environmental assessment for flumetralin for the purpose
of making a reregi strati on decision. A summary of the environmental risk assessment
findings and conclusions is provided below. For more detail on the flumetralin
environmental exposure and risk assessment, refer to the Environmental Fate and
Ecological Risk Assessment in Support of the Reregistration Eligibility Decision for
Flumetralin, dated July 10, 2007, which is available in the public docket.
1. Environmental Fate and Transport
Based on Koc values, flumetralin is hardly mobile to immobile (FAO Mobility
Classes; Koc range of 24,000-183,000) and is very persistent in aerobic soil, with a half-
life of longer than 3 years in one foreign soil. In an anaerobic foreign soil, flumetralin
degraded with a half-life of 42 days. Soil metabolism data obtained using U.S. soils were
classified as "not acceptable." Flumetralin is stable to hydrolysis. All data submitted to
assess photodegradation in water and on soil were classified as "not acceptable," so it is
unknown whether that might be a significant potential route of degradation in the
environment. Although both of the submitted terrestrial field dissipation studies were
classified as "supplemental" for multiple reasons, the available parent concentration data
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indicate that persistence and accumulation of the parent compound may be expected in
the field. Also, some leaching (to the 15- to 30-cm depth) was observed in one of the two
field studies. Submitted bioaccumulation data were also classified as "not acceptable," so
the potential for flumetralin to bioaccumulate in aquatic organisms is not well defined.
There is a potential for flumetralin to reach surface water through spray drift or,
because it is persistent in surface soils, through runoff either in solution or adsorbed to
the soil. However, most soils used to grow tobacco undergo conventional tillage and
flumetralin remaining on surface soils may move to subsurface soils where it could be
expected to degrade or remain adsorbed to soil.
Based on the results of a terrestrial field dissipation study, in which leaching was
observed (to 15-30 cm), flumetralin appears to have some potential to leach to
groundwater. However, these results conflict with those of laboratory mobility studies
which indicate high levels of adsorption to soil. Any potential to leach may be greater
when there is an excessive rainfall or irrigation event, particularly if either of these occurs
close to the time of application. Also, because adsorption of flumetralin is highly
correlated to organic matter content, there may be a greater potential for leaching in
lower organic matter soils, such as those used to grow tobacco.
2. Ecological Exposure and Risk
In ecological risk assessments, the ecological effects characterization describes the
types of effects a pesticide can potentially produce in an animal or plant. This
characterization is generally based on registrant-submitted studies that describe acute and
chronic effects information for various aquatic and terrestrial animals and plants;
however, these data may also be supplemented by data reported in ECOTOX or
open/public literature sources that have met Agency criteria for acceptability.
Toxicity testing reported in this section does not include all species potentially
affected by flumetralin usage. Only a few species for fish, aquatic invertebrates and birds
are used to represent all species in the United States. For mammals, toxicity studies are
limited to the laboratory rat. Also, neither reptiles nor amphibians are tested. The risk
assessment assumes that estimates of risks to avian species are protective of reptilian and
terrestrial-phase amphibians. The same assumption is used for fish and aquatic-phase
amphibians. Terrestrial plant data are derived from the vegetative vigor and seedling
emergence tests, typically on 10 agricultural crop species, and do not account for
potential chronic or reproductive effects. Typically, five aquatic plant species are used to
represent potential toxicity to all aquatic plant species.
Most of the studies with non-target organisms were conducted with flumetralin
technical. A typical end-use product (TEP), Prime+®, was the test material in the
terrestrial plant seedling emergence and vegetative vigor studies. These studies provide
the effects basis for risk estimation. The acute and chronic toxicity endpoints used in this
risk assessment are summarized in Table 7.
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Based on available data, ecological risk for most tested species from flumetralin is
below the Agency's level of concern. Although flumetralin toxicity is classified as high
for fish and invertebrates in laboratory studies, the limited use pattern for this chemical
limits exposure, and potential risk. Only 60,000 pounds of flumetralin are used annually;
it is applied only to tobacco and only once per year.
a) Terrestrial Organisms
Avian Acute Oral Dietary and Chronic
The acute oral toxicity of flumetralin to the mallard duck (Anas platyrhynchos) and
Northern bobwhite quail (Colinus virginiand) was assessed in separate single-dose
studies with 21-day observation periods. Birds were dosed at 1450 and 2150 mg ai/kg-
bw. No mortalities or adverse effects were observed in either study. The NOAEL and
LDso are 2150 and >2150 mg ai/kg-bw, respectively. Flumetralin is classified as
practically non-toxic to birds on an acute oral exposure basis.
The subacute dietary toxicity of flumetralin to the mallard duck and Northern
bobwhite quail was assessed over eight days. Flumetralin was administered to the birds
in the diet at mean-measured levels of 225, 560, 1220, 3050 and 4800 mg ai/kg diet. No
mortalities or adverse effects were observed in either study. The NOAEC and LCso were
4800 and >4800 mg ai/kg diet, respectively. Flumetralin is classified as practically non-
toxic to bobwhite quail and mallard duck on an acute dietary exposure basis.
No studies evaluating the chronic toxicity of flumetralin to birds have been submitted.
Mammalian Acute and Chronic
In an acute limit study on rats (Rattus norvegicus; MRID 00093998) reviewed by the
Health Effects Division, flumetralin was administered by gavage to five male and five
female albino rats. The rats were observed for 15 days, with no mortality. Some nasal
bleeding was observed in male rats; no other clinical signs were observed. The acute oral
LD50 value was >5000 mg ai/kg-bw. Flumetralin is classified as practically nontoxic to
rats on an acute oral exposure basis.
In a 2-generation reproduction study (MRID 00149532), flumetralin was
administered via the diet to groups of 15 male and 30 female CD-Crl:CD (SD)BR rats per
group at dose levels of 0, 30, 300, 1000, or 1500 ppm. The premating period of dosing
was 15 weeks [FOJ/18 weeks [Fl]. The Fl parents were bred twice. Mating was
accomplished by cohabitating one male with two females for up to 14 days [F0]/21 days
[Fl]. Although there were several deaths, there was no dose response. All of the control
animals survived, but two FO females at 30 ppm and 1500 ppm, one FO female at 1000
ppm, one Fl male at 30 ppm and 300 ppm, two Fl males at 1500 ppm, one Fl female at
300 ppm and 1000 ppm, and two Fl females at 1500 ppm died. The only clinical sign
noted was an orange coloration of the urine and fat tissue, which was attributed to the test
material color (yellow-orange crystals).
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The parental toxicity NOAEL is 300 ppm based on a slight decrease in body weight
(-10%) during the dosing period and throughout gestation and lactation at 1000 ppm.
The offspring systemic toxicity NOAEL is 1000 ppm based on decreased body weight of
pups. The reproductive toxicity NOAEL is 1500 ppm, which was the highest dose tested.
Chronic effects to mammals are mainly associated with parental weight loss; there were
no reproductive effects.
Non-target Invertebrates
In a 48-hour acute contact toxicity study (MRID 41761507), honey bees were
exposed to flumetralin, administered topically at the nominal rates of 6.25, 12.5, 25, 50
and 100 ug ai/bee. There was 10% mortality in the 100 ug ai/bee treatment level and 2%
in the 25 ug ai/bee treatment level. No abnormal behavior was reported. Based on the
48-hour LCso of > 100 ug ai/bee, flumetralin is classified as practically non-toxic to honey
bees on an acute contact basis.
Terrestrial Plants
In a 21-day seedling emergence study, a total of four monocotyledonous species (corn
(Zea mays), oat (Avena sativd), onion (Allium cepa) and ryegrass (Lolium spp.)) and six
dicotyledonous species (carrot (Daucus carota), cucumber (Cucumis sativus), cabbage
(Brassica oleracea), soybean (Glycine max), lettuce (Lactuca saliva) and tomato
(Lycopersicon esculentum)) were exposed to a single application of the TEP, Prime+® at
rates from 0.019 Ibs ai/A to 1.2 Ibs ai/A. A continuation study was conducted, at rates as
low as 0.0003 Ibs ai/A. There was no effect on emergence or survival in any species
except rye grass, the most sensitive species in the study. Plant height was unaffected in
soybean, carrot and corn; biomass was unaffected in soybean, carrot, corn, oat cabbage
and onion. The most sensitive species is ryegrass with an £€25 of 0.006 Ibs ai/A and the
NOEC is 0.0048 Ibs ai/A, based on plant height. The most sensitive dicot was tomato,
based on biomass, with an £€25 of 0.039 Ibs ai/A and a NOEC of 0.019 Ibs ai/A.
A vegetative vigor study was conducted using the same rates and species as the
seedling emergence study. There was no effect on the plant height of carrot and corn,
and no effect on the biomass of carrot, oat, corn and onion. The most sensitive dicot,
based on plant height, was tomato with an EC25 of 0.014 Ibs ai/A and a NOEC of 0.0048
Ibs ai/A. The most sensitive monocot species (based on biomass) was ryegrass, with an
EC25 of 0.027 Ibs ai/A and a NOEC of 0.019 Ibs ai/A.
b) Aquatic Organisms
Freshwater Fish
In a 96-hour acute toxicity study (MRID 43456601), bluegill sunfish (Lepomis
macrochirus) were exposed to flumetralin at mean-measured concentrations of 6.0, 7.8,
18, 33 and 58 ug ai/L. No mortality was observed in the two lowest concentrations;
Page 23 of 54
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mortalities of 15, 95 and 100% were observed in the 18, 33 and 58 jig ai/L
concentrations, respectively. Sublethal effects (loss of equilibrium, erratic swimming
behavior) were observed in the range-finding study at concentrations as low as 13 jig
ai/L; sublethal effects were not reported at the lowest concentration in the definitive
study. The 96-h LCso and NOAEC values, based on mortality, were 23 and 7.8 jig ai/L,
respectively. Flumetralin is classified as very highly toxic to freshwater fish on an acute
exposure basis.
The chronic toxicity of flumetralin to fathead minnow (Pimephalespromelas; MRID
00116598) was assessed in a 38-day study, conducted under flow-through conditions.
The fish were exposed to the mean-measured concentrations of 0.46, 0.77, 2.4, 3.8, and
20 jig ai/L. Percent hatch was unaffected (>77%) at all treatment concentrations.
Survival was significantly reduced at the 3.8 and 20 jig ai/L concentrations (20% and 0%
survival, respectively). Both mean length and mean wet weight were significantly
reduced at the 2.4 and 3.8 jig ai/L treatment concentrations (there were no surviving fish
to measure in the highest test concentration). The 38-day NOAEC, based on length and
weight, was 0.77 jig ai/L.
Although flumetralin exhibits both acute and chronic toxicity to freshwater fish in
laboratory studies, environmental exposure is limited and thus risk quotients are below
the level of concern, except for listed species.
Freshwater Invertebrates
An acute 48-hour static toxicity study was conducted to determine the effects of
flumetralin on daphnids (Daphnia magna; MRID 43456602). The mean-measured test
concentrations were 33, 47, 69, 100 and 160 jig ai/L. At 48 hours, there was 10, 15 and
5% immobilization observed in the 69, 100 and 160 jig ai/L concentrations, respectively.
Therefore, the 48-h EC50 value was >160 |ig ai/L and the 48-h NOAEC was 33 |ig ai/L.
Flumetralin is classified as very highly toxic to daphnids on an acute exposure basis.
A chronic 21-day (life-cycle) flow-through toxicity study (MRID 00116600) was
conducted to determine the effects of flumetralin on daphnids. The nominal test
concentrations were 0.63, 0.91, 2.1, 3.8 and 8.8 jig ai/L, to which first instars were
exposed. There were no effects on growth, survival or reproduction reported at any test
concentration. The 21-day NOAEC was 8.8 jig ai/L.
Although flumetralin exhibits acute toxicity to freshwater invertebrates in laboratory
studies, environmental exposure is limited and thus risk quotients are below the level of
concern.
Estuarine/Marine Fish
In an acute flow-through toxicity study, sheepshead minnow (Cyprinodon variegatus;
MRID 43456603) were exposed to flumetralin at mean measured concentrations of 40,
51, 80, 140 and 250 jig ai/L; mortality was reported at all concentrations (5, 25, 10, 5 and
Page 24 of 54
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5%, respectively). Surviving fish were reported to exhibit loss of equilibrium at all
concentrations. Therefore, the 96-hour LCso and NOAEC values were >250 and <40 jig
ai/L, respectively. Flumetralin is classified as highly toxic to estuarine/marine fish on an
acute exposure basis.
No data are available to evaluate chronic effects to estuarine/marine fish.
Although flumetralin exhibits acute toxicity to estuarine/marine fish in laboratory
studies, environmental exposure is limited and thus risk quotients are below the level of
concern.
Estuarine/Marine Invertebrates
A 96-hour acute toxicity study was conducted under flow-through conditions to
determine the effect of flumetralin on mysid shrimp (Mysidopsis bahia; MRID
43456605). The shrimp were exposed to mean measured concentrations of 33, 34, 58, 71
and 180 jig ai/L. Immobilization was 35 and 95% and in the two highest concentrations
respectively. Erratic swimming was observed at concentrations as low as 34 jig ai/L
(although no effect was reported in the 33 jig ai/L concentration). The 96-hour ECso and
NOAEC were 93 and 33 jig ai/L, respectively. Flumetralin is classified as very highly
toxic to the mysid shrimp on an acute exposure basis.
A 96-hour acute toxicity study was conducted under flow-through conditions to
determine the effect of flumetralin on Eastern oysters (Crassostrea virginica; MRID
43456604). The oysters were exposed to mean measured concentrations of 7.1, 18, 45,
180 and 550 jig ai/L. No mortality was observed at any concentration tested, but shell
deposition was significantly reduced at the highest test concentration (28%). The 96-
hour ECso and NOAEC were reported as 600 and 100 jig ai/L, respectively. Flumetralin
is classified as highly toxic to the Eastern oyster on an acute exposure basis.
No data are available to evaluate chronic effects to estuarine/marine invertebrates.
Although flumetralin exhibits acute toxicity to estuarine/marine invertebrates in
laboratory studies, environmental exposure is limited and thus risk quotients are below
the level of concern.
Aquatic Plants
In a 14-day static toxicity test, duckweed (Lemna gibba; MRID 434566-06) was
exposed to flumetralin at initial measured concentrations of 8.2, 16, 30, 60, 71, 130 and
220 jig ai/L. After 14 days, inhibition of frond production ranged from 4.5% at 8.2 jig
ai/L to 59% at 220 jig ai/L when compared to the solvent control. Inhibition in biomass
ranged from 7% to 35% at the highest dose. The NOEC and ECso values, based on frond
production, are 16 and 160 jig ai/L, respectively.
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No studies are available to evaluate the effect of flumetralin on nonvascular aquatic
plants.
Table 6 lists the most sensitive endpoints used in the flumetralin risk assessment.
Table 6: The Most Sensitive Endpoints Used in the Flumetralin Risk Assessment
Environment
Aquatic
Terrestrial
Taxa
Freshwater Fish
Freshwater
Invertebrates
Estuarine/Marine
Fish
Estuarine/Marine
Invertebrates
Plants
Avian
Mammalian
Plants
Type
of Risk
Acute
Chronic
Acute
Chronic
Acute
Chronic
Acute
Chronic
Acute
Listed
Acute
Chronic
Acute
Chronic
Acute
Listed
Type of
Endpoint
LC50
NOAEC
EC50
NOAEC
LC50
NOAEC
EC50
NOAEC
EC50
NOAEC
LD50
NOAEC
LD50
NOAEC
EC25
NOAEC
Endpoint
23
0.77
>160
>8.8
>250
No data
93
No data
160
16
2150
No Data
>5000
300
0.006
0.0048
Units
ugai/L
ugai/L
ugai/L
ugai/L
ugai/L
ugai/L
ugai/L
ugai/L
mg ai/kg-bw
mg ai/kg-diet
mg ai/kg-bw
mg ai/kg-diet
Ibai/A
Ibai/A
MRID
434566-01
001165-98
434566-02
001166-00
434566-03
434566-05
434566-06
434566-06
000940-16
000939-98
001495-32
418470-01
418470-01
c) Risk Characterization
The risk quotient (RQ) approach is used in this assessment to reach conclusions
regarding the potential for adverse effects associated with the proposed use of
flumetralin. The basis of the RQ approach is a comparison of the ratio of exposure
concentrations to effects endpoints with predetermined levels of concern (LOCs).
Specifically, estimated environmental concentrations (EECs) are divided by acute and
chronic toxicity values to calculate RQs. If the RQs exceed the LOCs, the Agency
presumes there is a potential to affect species in that taxa. Laboratory environmental
fate, laboratory ecological effects, and use data provide the basis for these risk quotients
and have been discussed previously in the assessment. Although risk is often defined as
the likelihood and magnitude of adverse ecological effects, the risk quotient-based
approach does not provide a quantitative estimate of likelihood and/or magnitude of an
adverse effect. These LOCs are indicators of whether a pesticide, used as directed on the
label, has the potential to cause adverse effects on non-target organisms.
Based on the most sensitive endpoint for each of the taxa evaluated, the RQ values for
acute effects to listed freshwater fish and chronic effects to mammals and for non-target
terrestrial plants exceed the LOG for flumetralin. No data are available to assess the risk
to aquatic nonvascular plants and chronic risk to birds.
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A summary of RQs is presented in Table 7.
Table 7: The Highest RQs for Listed Taxa in the Flumetralin Risk Assessment
Environment
Aquatic
Terrestrial
Taxa
Freshwater
Fish
Freshwater
Invertebrates
Vascular
Plants
Avian
Mammalian
Plants
Type
of Risk
Acute
Chronic
Acute
Chronic
Acute
Listed
Acute
Chronic
Acute
Chronic
Acute
Listed
Type of
Endpoint
LCso
NOAEC
ECso
NOAEC
ECso
NOAEC
LD50
NOAEC
LD50
NOAEC
EC25
NOAEC
Endpoint
23
0.77
160
8.8
160
16
2150
No Data
>5000
300
0.006
0.0048
Units
Ugai/L
Ugai/L
|ig ai/L
|ig ai/L
|ig ai/L
Ugai/L
mg ai/kg-bw
mg ai/kg-diet
mg ai/kg-bw
mg ai/kg-diet
Ib ai/A
Ib ai/A
RQ
0.10
0.43
<0.01
<0.05
0.00001
0.000001
No effects
No data
No effects
6.0
22
27.5
The Agency has considered the ecological risks associated with the use of
flumetralin. Based on the EPA's baseline assessment and taking into account its limited
use pattern, the use of flumetralin according to label directions should not result in direct
acute or chronic effects to fish, aquatic invertebrates or aquatic vascular plants. The LOG
for direct acute effect to listed freshwater fish (and aquatic-phase amphibians) is
exceeded. Although there are no data regarding the chronic effects to estuarine/marine
animals, acute-to-chronic ratio analysis suggests potential risk to these organisms will be
low. Risk is presumed for aquatic nonvascular plants in the absence of data. The
potential for acute risk to birds and mammals appears to be low. There is potential for
chronic risk to mammals, and chronic risk to birds, terrestrial-phase amphibians and
reptiles is presumed in the absence of avian chronic toxicity data. Indirect effects to
terrestrial or aquatic wildlife cannot be ruled out due to the potential for flumetralin to
affect terrestrial and semi-aquatic plants which may lead to changes in food supply or
habitat.
d) Endangered Species
The Agency has developed 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 address these impacts. The Endangered
Species Act (ESA) requires federal agencies to ensure that their actions are not likely to
jeopardize listed species or adversely modify designated critical habitat. To analyze the
potential of registered pesticide uses that may affect any particular species, EPA uses
basic toxicity and exposure data and considers ecological parameters, pesticide use
information, geographic relationship between specific pesticide uses and species
locations, and biological requirements and behavioral aspects of the particular species.
When conducted, these analyses take into consideration any regulatory changes
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recommended in this RED being implemented at that time.
The ecological assessment that EPA conducted for this RED does not, in itself,
constitute a determination as to whether specific species or critical habitat may be harmed
by the pesticide. Rather, this assessment serves as a screen to determine the need for any
species-specific assessment that will evaluate whether exposure may be at levels that
could cause harm to specific listed species and their critical habitat. The species-specific
assessment refines the screening-level assessment to take into account information such
as the geographic area of pesticide use in relation to the listed species and the habits and
habitat requirements of the listed species. If the Agency's specific assessments for
flumetralin result in the need to modify use of the pesticide, any geographically specific
changes to the pesticide's registration will be implemented through the process described
in the Agency's Federal Register Notice (54 FR 27984) regarding implementation of the
Endangered Species Protection Program.
IV. Risk Management and Reregistration Decision
The Agency has determined that flumetralin is eligible for reregi strati on provided that
the risk mitigation measures and label amendments specified in this RED are
implemented. The following is a summary of the rationale for managing risks associated
with the use flumetralin.
A. Human Health Risks
No human health risks of concern were identified for flumetralin.
The current REI on flumetralin labels is 24 hours. Based on the toxicity category III
assigned to the most recent acceptable primary eye irritation studies, the REI on
flumetralin labels may be decreased to 12 hours.
Due to a residue chemistry data deficiency, all product labels must be modified to
establish a 10-month plantback interval for all crops. If the registrant wants to establish a
plantback interval shorter than 10 months, a confined rotational crop study with
flumetralin must be conducted.
B. Ecological Risks
Due to the high persistence of flumetralin in the environment and to reduce potential
ecological exposure to flumetralin, the following statements must be added to the
flumetralin label:
The following statements must be added to the "Environmental Hazards" statements
on the lab el:
• "The product is toxic to fish and aquatic invertebrates. Do not apply to water, or
to areas where surface water is present, or to areas below the mean high water
mark. Do not contaminate water when disposing of equipment washwater or
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rinsate. Drift and runoff may be hazardous to aquatic organisms in water adjacent
to treated areas."
• "This product has a potential for runoff for several months or more after
application. Poorly draining soils and soils with shallow water tables are more
prone to produce runoff that contains this product. A level, well maintained
vegetative buffer strip between areas to which this product is applied and surface
water features such as ponds, streams and springs will reduce the potential for
contamination of water from runoff. In order to reduce runoff of this product it is
recommended that applications are not made within 48 hours of a predicted
rainfall event. Sound erosion control practices will reduce this product's
contribution to surface water contamination."
The following statements must be added to the "Spray Drift" statements on the label:
• "Non-target terrestrial plants can be adversely affected when exposed to this
product. Avoid spray drift to non-target terrestrial plants during application.
• Do not apply this product if the wind direction does not favor on-target
deposition."
• "Must not be applied greater than 4 feet above crop or crop canopy."
Also, the current requirement for a "coarse" spray must be maintained on all
flumetralin labels.
V. What Registrants Need to Do
The Agency has determined that products containing flumetralin (PC 123001) are
eligible for reregi strati on provided that the risk mitigation measures identified in this
document are adopted and label amendments are made to reflect these measures.
Additional data are required to fill data gaps identified and to confirm this decision. The
Agency intends to issue Data Call-In Notices (DCIs) requiring product specific data and
generic (technical grade) data. Generally, registrants will have 90 days from receipt of a
DCI to complete and submit response forms or request time extension and/or waiver
requests with a full written justification. For product specific data, the registrant will
have 8 months to submit data and amend labels. For generic data, due dates can vary
depending on the specific studies being required.
A. Manufacturing Use Products
1. Additional Generic Data Requirements
The generic database supporting the reregi strati on of flumetralin has been reviewed.
The risk assessments identified the potential need for certain ecological, environmental
fate, and residue chemistry data. The studies are as follows:
• Direct Photolysis Rate of Parent and Degradates in Water
• Photodegradation of Parents and Degradates in Soil
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• Aerobic Aquatic Metabolism
• Anaerobic Aquatic Metabolism
• Terrestrial Field Dissipation
• Fish BCF
• Whole Sediment Acute Toxicity Invertebrates, Freshwater
• Avian Reproduction Test
• Aquatic Plant Toxicity Test Using Lemmna spp. Tiers I and II
• Aquatic Plants Field Study, Tier III
• Confined Accumulation in Rotational Crops
However, the Agency may be refining these data requirements based on the limited
annual usage and use pattern for this chemical.
2. Labeling for Technical and Manufacturing Use Products
To ensure compliance with FIFRA, technical and manufacturing use product (MP)
labeling should be revised to comply with all current EPA regulations, PR Notices and
applicable policies. In order to be eligible for reregi strati on, the technical registrants also
must amend all product labels to incorporate the risk mitigation measures outlined in
Section IV. The technical and MP labeling should also bear the labeling statements
contained in Table 8, the Label Changes Summary Table.
B. End-Use Products
1. Additional Product-Specific Data Requirements
Section 4(g) (2) (B) of FIFRA calls for the Agency to obtain any needed product-
specific data regarding a pesticide after a determination of eligibility has been made. The
registrant must review previous data submissions to ensure 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 the study MRID numbers
should be cited according to the instructions in the Requirement Status and Registrations
Response Form provided for each product.
A product-specific data call-in, outlining specific data requirements will be issued in
the near future.
2. Labeling for End-Use Products
Labeling changes are necessary to implement measures outlined in Section IV above.
Specific language to incorporate these changes is specified in Table 8, the Label Changes
Summary Table.
Page 30 of 54
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In order to be eligible for reregistration, amend all product labels to incorporate the risk mitigation measures outlined in Section IV. The following
table describes how language on the labels should be amended.
Table 8: Summary of Labeling Changes for Flumetralin
Description
Amended Labeling Language
Placement on Label
For all Manufacturing
Use Products
"Only for formulation into a plant growth regulator for use on tobacco."
Directions for Use
One of these statements
may be added to a label
to allow reformulation
of the product for a
specific use or all
additional uses
supported by a
formulator or user
"This product may be used to formulate products for specific use(s) not
listed on the MP label if the formulator, user group, or grower has
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 MP label if the formulator, user group, or grower
has complied with U.S. EPA submission requirements regarding support
of such use(s)."
Directions for Use
Environmental Hazards
Statements Required
by the RED and
Agency Label Policies
"Do not discharge effluent containing this product into lakes, streams,
ponds, estuaries, oceans, or other waters unless in accordance with the
requirements of a National Pollution Discharge Elimination System
(NPDES) permit and the permitting authority has been notified in writing
prior to discharge. Do not discharge effluent containing this product to
sewer systems without previously notifying the local sewage treatment
plant authority. For guidance contact your State Water Board or
Regional Office of the EPA."
Precautionary Statements
31
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End Use Products Intended for Occupational Use
PPE Requirements
Established by the
RED1
For Liquid
Formulations
"Personal Protective Equipment (PPE)"
"All mixers, loaders, applications and other handlers must wear:
- Long sleeved shirt,
- Long pants,
- Shoes plus socks."
Immediately following/below
Precautionary Statements: Hazards to
Humans and Domestic Animals
User Safety
Requirements
"Follow manufacturer's instructions for cleaning/maintaining PPE. If no
such instructions for washables exist, use detergent and hot water. Keep
and wash PPE separately from other laundry."
"Discard clothing and other absorbent materials that have been drenched
or heavily contaminated with this product's concentrate. Do not reuse
them."
Precautionary Statements: Hazards to
Humans and Domestic Animals
immediately following the PPE
requirements
User Safety
Recommendations
"User Safety Recommendations
Users should wash hands before eating, drinking, chewing gum, using
tobacco, or using the toilet.
Users should remove clothing/PPE immediately if pesticide gets inside.
Then wash thoroughly and put on clean clothing.
Users should remove PPE immediately after handling this product. Wash
the outside of gloves before removing. As soon as possible, wash
thoroughly and change into clean clothing."
Precautionary Statements under:
Hazards to Humans and Domestic
Animals immediately following
Engineering Controls
(Must be placed in a box.)
32
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Environmental Hazards
"The product is toxic to fish and aquatic invertebrates. Do not apply to
water, or to areas where surface water is present, or to areas below the
mean high water mark. Do not contaminate water when disposing of
equipment washwater or rinsate. Drift and runoff may be hazardous to
aquatic organisms in water adjacent to treated areas."
"This product has a potential for runoff for several months or more after
application. Poorly draining soils and soils with shallow water tables are
more prone to produce runoff that contains this product. A level, well
maintained vegetative buffer strip between areas to which this product is
applied and surface water features such as ponds, streams and springs
will reduce the potential for contamination of water from runoff. In order
to reduce runoff of this product it is recommended that applications are
not made within 48 hours of a predicted rainfall event. Sound erosion
control practices will reduce this product's contribution to surface water
contamination."
Precautionary Statements immediately
following the User Safety
Recommendations
Restricted-Entry
Interval for products
with directions for use
within scope of the
Worker Protection
Standard for
Agricultural Pesticides
(WPS)
"Do not enter or allow worker entry into treated areas during the
restricted entry interval (REI) of 12 hours.
Directions for Use, Under Agricultural
Use Requirements Box
Early Entry Personal
Protective Equipment
for products with
directions for use
within the scope of the
WPS
"PPE required for early entry to treated areas that is permitted under the
Worker Protection Standard and that involves contact with anything that
has been treated, such as plants, soil, or water, is:
* coveralls,
* shoes plus socks
* chemical-resistant gloves made of any waterproof material."
Direction for Use
Agricultural Use Requirements box
33
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General Application
Restrictions
"Do not apply this product in a way that will contact workers or other
persons, either directly or through drift. Only protected handlers may be
in the area during application."
Place in the Direction for Use directly
above the Agricultural Use Box.
Spray Drift
"SPRAY DRIFT MANAGEMENT
"Non-target terrestrial plants can be adversely affected when exposed to
this product. Avoid spray drift to non-target terrestrial plants during
application.
Do not apply this product if the wind direction does not favor on-target
deposition."
"Must not be applied greater than 4 feet above crop or crop canopy."
Directions for Use
Additional Application
Restrictions
All product labels must be modified to establish a 10-month plantback
interval for all crops other than tobacco.
Directions for Use
1 PPE that is established on the basis of Acute Toxicity of the end-use product must be compared to the active ingredient PPE in this document.
The more protective PPE must be placed in the product labeling. For guidance on which PPE is considered more protective, see PR Notice 93-7.
2 If the product contains oil or bears instructions that will allow application with an oil-containing material, the "N" designation must
be dropped.
34
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I. APPENDIX A. USE PATTERNS SUBJECT TO REREGISTRATION OF FLUMETRALIN (PC CODE 123001)
Use Site
Application
Timing
Maximum
Application Rate
Formulation2
Maximum
Number of
Applications
per Year
Minimum
Application
Interval
Application Equipment /Type
TERRESTRIAL NON-FOOD USES
tobacco
crops
typically
applied
between 3
and 7 days
after the floral
portion of
tobacco
plants have
been topped
1.2 Ib. a.i./acre
emulsifiable
concentrate
1
NA
hand spray or ground spray
(groundboom, LP handwand, and
backpack sprayer)
35
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II. APPENDIX B. TABLE OF GENERIC DATA REQUIREMENTS AND STUDIES USED TO MAKE THE
REREGISTRATION DECISION
GUIDE TO APPENDIX B
Appendix B contains a listing of data requirements which support the reregi strati on for active ingredients within the
flumetralin case covered by this RED. It contains generic data requirements that apply flumetralin in all products, including data
requirements for which a "typical formulation" is the test substance.
The data table is organized in the following formats:
1. Data requirement (Column 1). The data requirements are listed in the order in which they appear in 40 CFR 158. The
reference numbers accompanying each test refer to the test protocols set in the Pesticide Assessment Guidance, which is
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
36
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M. Indoor non-food
N. Indoor medical
O. Indoor residential
3. Bibliographic Citation (Column 3). If the Agency has acceptable data in its files, this column lists the identifying number of each
study. This normally is the Master Record Identification (MRID) number, but may be a "GS" number is no MRID number has been
assigned. Refer to the Bibliography appendix for a complete citation of the study.
37
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Appendix B. Table of Generic Data Requirements and Studies Used to Make the Reregi strati on Decision
Data Supporting Guideline Requirements for the Reregistration of Flumetralin
New
Guideline
Number
Study Description
Use
Pattern
Citation(s)
TOXICOLOGY
PRODUCT CHEMISTRY
830.6302
830.6304
830.6313
830.6314
830.7000
830.7200
830.7300
830.7370
830.7550
830.7840
830.7950
Color
Physical state
Stability
Oxidation/Reduction Potential
pH
Melting Point
Density
Dissociation Constants in Water
Octanol Water Partition Coefficient
Solubility
Vapor Pressure
All
All
All
All
All
All
All
All
All
All
All
Data Gap
Data Gap
Data Gap
Data Gap
Data Gap
Agrochemicals Handbook, 2nd Edition, RSC,
Nottingham, UK 1987
(wwj¥jirajsd^^
Data Gap
Data Gap
Pesticide Manual, 10th Ed., British Crop
Protection Council, and The Royal Society Of
Chemistry, 1994
(www.arsusda.gov/acsl/services/ppdb).
Pesticide Manual, 10th Ed., British Crop
Protection Council, and The Royal Society Of
Chemistry, 1994
(www.aBiisda.eov/acsl/scwiccs/ppdb).
Pesticide Manual, 10th Ed., British Crop
Protection Council, and The Royal Society Of
Chemistry, 1994
(www.arsusda.gov/acsl/services/ppdb).
ECOLOGICAL EFFECTS
38
-------
Data Supporting Guideline Requirements for the Reregistration of Flumetralin
New
Guideline
Number
850.1010
850.1025
850.1035
850.1075
850.1075
Non-
Guideline
850.1350
850.1400
850.1500
850.2100
850.2200
850.2300
850.3020
850.4225
850.4250
850.4400
Study Description
Freshwater Aquatic Invertebrate
Acute Toxicity - Daphnid
Estuarine/Marine Invertebrate Acute
Toxicity - Oyster
Estuarine/Marine Invertebrate Acute
Toxicity - Mysid
Freshwater Fish Acute Toxicity -
Bluegill Sunfish
Estuarine/Marine Fish Acute
Toxicity - Sheepshead Minnow
Freshwater Aquatic Invertebrate
Chronic Toxicity - Daphnid
Estuarine/Marine Invertebrate
Chronic Toxicity
Freshwater Fish Chronic Toxicity -
Fathead Minnow
Estuarine/Marine Fish Chronic
Toxicity
Avian Acute Oral Toxicity
Avian Dietary Toxicity
Avian Reproduction
Honey Bee Acute Contact Toxicity
Seedling Emergence, Tier II
Vegetative Vigor, Tier II
Aquatic Plant Toxicity Test, Tiers I
and II - Lemna gibba
Use
Pattern
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
Citation(s)
43456602
43456604
43456605
43456601
43456603
00116600
Data Gap
00116598
Data Gap
00094016
Data Gap
Data Gap
41761507
41847001
41847001
Data Gap
39
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Data Supporting Guideline Requirements for the Reregistration of Flumetralin
New
Guideline
Number
850.4450
850.5400
Study Description
Aquatic Plants Field Toxicity,
Tier III
Algal Plant Toxicity, Tiers I and II
Use
Pattern
All
All
Citation(s)
Data Gap
Data Gap
TOXICOLOGY
870.1100
870.1200
870.1300
870.2400
870.2500
870.2600
870.3100
870.3150
870.3200
870.3465
870.3700A
870.3700B
870.3800
Acute Oral Toxicity - Rat
Acute Dermal Toxicity - Rabbit
Acute Inhalation Toxicity - Rat
Primary Eye Irritation - Rabbit
Primary Dermal Irritation - Rabbit
Skin Sensitization - Guinea Pig
Subchronic Oral Toxicity: 90-Day
Study Rodent
Subchronic Oral Toxicity -
Nonrodent
2 1/2 8 -Day Dermal Toxicity -
Rabbit
90-Day Inhalation Toxicity (Fischer
344 rat) - Non-Guideline Smoking
Study
Developmental Toxicity - Rat
Developmental Toxicity - Rabbit
Reproduction and Fertility Effects
(CD-Crl:CD(SD)BRrats)
All
All
All
All
All
All
All
All
All
All
All
All
All
00093998
00093999
00094002
00094000
00104250
00094001
00094013
00094012
00116594
00117622
00094011
43862801
00149532, 00145793
40
-------
Data Supporting Guideline Requirements for the Reregistration of Flumetralin
New
Guideline
Number
870.4100a
870.4200
870.4300
870.5265
870.5385
870.5550
Study Description
Chronic toxicity (SD Rat)
Carcinogenicity (Rat)
Carcinogenicity (Mouse)
Gene Mutation - Ames Assay
Micronucleus Assay (Mouse)
Other Effects - Rat
Hepatocyte/DNA Repair Test - UDS
Use
Pattern
All
All
All
All
All
All
Citation(s)
42061603,42061604
42061603,42061604
42061601,42061602
00094009
00094010
42061605
ENVIRONMENTAL FATE
835.1240
835.2120
835.2240
835.2410
835.4100
835.4200
835.4300
835.4400
835.6100
850.1730
Leaching/Adsorption/Desorption
Hydrolysis
Direct Photolysis Rate of Parent and
Degradates in Water
Photodegradation of Parent and
Degradates in Soil
Aerobic Soil Metabolism
Anaerobic Soil Metabolism
Aerobic Aquatic Metabolism Half-
life (days)
Anaerobic Aquatic Metabolism
Half-life (days)
Terrestrial Field Dissipation
Fish BCF
All
All
All
All
All
All
All
All
All
All
Data Gap
41761508
Data Gap
Data Gap
425 6620 la (supplemental - from foreign
soil; no U.S. data available)
4256620 Ib (supplemental - from foreign
soil; no U.S. data available)
Data Gap
Data Gap
Data Gap
Data Gap
RESIDUE CHEMISTRY
41
-------
Data Supporting Guideline Requirements for the Reregistration of Flumetralin
New
Guideline
Number
860.1850
Study Description
Confined Rotational Crops
Use
Pattern
All
Citation(s)
Data Gap
42
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III. APPENDIX C. TECHNICAL SUPPORT DOCUMENTS
Additional documentation in support of this RED is maintained in the OPP docket EPA-HQ-OPP-2007-0990. This docket
may be accessed in the OPP docket room located at Room S-4900, One Potomac Yard, 2777 S. Crystal Drive, Arlington, VA. It is
open Monday through Friday, excluding Federal holidays, from 8:30 a.m. to 4:00 p.m. All documents may be viewed in the OPP
docket room or downloaded or viewed via the Internet at the following site: http://www.regulations.gov.
These documents include:
HEP Documents:
Flumetralin: Revised HED Chapter of the Reregistration Eligibility Decision Document (RED). Dated June 21, 2007.
Flumetralin: Addendum to HED Chapter of the Reregistration Eligibility Decision Document (RED). Dated September 20, 2007.
Flumetralin: Occupational and Residential Exposure Assessment for the Reregistration Eligibility Decision. Dated March 28, 2007.
Flumetralin. Residue Chemistry Chapter of the Reregistration Eligibility Decision Document. Dated April 2, 2007.
Flumetralin Acute and Intermediate Term Dietary (Drinking Water Only) Exposure and Risk Assessments for the Reregistration
Eligibility Decision. Dated June 21, 2007.
EFED Documents:
Environmental Fate and Ecological Risk Assessment in Support of the Reregistration Eligibility Decision for Flumetralin. Dated July
10, 2007.
EFED Response to Error Only Comments and the Revised Environmental Fate and Ecological Risk Assessment in Support of the
Reregistration Eligibility Decision of Flumetralin. Dated September 13, 2007.
Tier II Drinking water Assessment for the Flumetralin Reregistration Eligibility Decision. Dated June 5, 2007.
43
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IV. APPENDIX D. CITATIONS CONSIDERED TO BE PART OF THE DATA BASE SUPPORTING THE
REREGISTRATION ELIGIBILITY DECISION
00093998 Reagan, E.L.; Becci, P.J.; Parent, R.A. (1981) Acute Oral Toxicity in Rats: (CGA-41065 Technical): FDRL Study No.
6818A. (Unpub- lished study received Jan 28, 1982 under 100-EX-72; prepared by Food and Drug Research
Laboratories, Inc., submitted by Ciba- Geigy Corp., Greensboro, NC; CDL:246679-B)
00093999 Becci, P.J.; Siglin, J.C.; Parent, R.A. (1981) Acute Dermal Toxicity Study in Rabbits: (CGA 41065 Technical): FDRL
Study No. 6818A. (Unpublished study received Jan 28, 1982 under 100-EX- 72; prepared by Food and Drug Research
Laboratories, Inc., submitted by Ciba-Geigy Corp., Greensboro, NC; CDL:246679-C)
00094000 Siglin, J.C.; Becci, P.J.; Parent, R.A. (1981) Primary Eye Irrita- tion Study in Rabbits: FDRL Study No. 6818IAA.
(Unpublished study received Jan 28, 1982 under 100-EX-72; prepared by Food and Drug Research Laboratories, Inc.,
submitted by Ciba-Geigy Corp., Greensboro, N.C.; CDL:246679-E)
00094001 Siglin, J.C.; Becci, P.J.; Parent, R.A. (1981) Guinea Pig Sensitization Study: Modified Buehler Test for Ciba-Geigy
Corporation Product CGA-41065 Technical; 96.4%; FL 810009: FDRL Study No. 6963B. (Unpublished study received
Jan 28, 1982 under 100- EX-72; prepared by Food and Drug Research Laboratories, Inc., submitted by Ciba-Geigy
Corp., Greensboro, N.C.; CDL:246679-F)
00094002 Morgan, J.M.; Horath, L.L.; Sabaitis, C.P.; et al. (1981) Four- hour Acute Aerosol Inhalation Toxicity Study in Rats of
CGA- 41065 Technical in Acetone: Study No. 420-0703. (Unpublished study received Jan 28, 1982 under 100-EX-72;
prepared by Whit- taker Corp., submitted by Ciba-Geigy Corp., Greensboro, N.C.; CDL:246679-G)
00094009 Godek, E.G.; Naismith, R.W.; Matthews, R.J. (1981) Ames Salmon- ella/Microsome Plate Test: Study Nos. PH 301-
CG-001-81 and PH 301-CG-001-81A. (Unpublished study received Jan 28, 1982 under 100-EX-72; prepared by
Pharmakon Research International, Inc., submitted by Ciba-Geigy Corp., Greensboro, N.C.; CDL: 246679-N)
44
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00094010 Sorg, R.M.; Naismith, R.W.; Matthews, RJ. (1981) Genetic Toxicol- ogy: Micronucleus Test (MNT): PH 309A-CG-
001-81. (Unpublished study received Jan 28, 1982 under 100-EX-72; prepared by Phar- makon Research International,
Inc., submitted by Ciba-Geigy Corp., Greensboro, N.C.; CDL:246679-O)
00094011 Harris, S.B.; Holson, J.F.; Fite, K.R.; et al. (1981) A Teratol- ogy Study of CGA-41065 Technical in Albino Rats:
CGA/SAI 281004. Final rept. (Unpublished study received Jan 28, 1982 under 100- EX-72; prepared by Science
Applications, Inc., submitted by Ciba-Geigy Corp., Greensboro, N.C.; CDL:246680-A)
00094012 Beck, L.S.; DeWard, J.; Kitchen, D.N.; et al. (1981) Six Month Sub- chronic Oral Toxicity Study with CGA-41065
Technical in Beagle Dogs: Project No. 1628. (Unpublished study received Jan 28, 1982 under 100-EX-72; prepared by
Elars Bioresearch Labora- tories, Inc. and Westpath Laboratories, Inc., submitted by Ciba-Geigy Corp., Greensboro,
N.C.; CDL:246682-A)
00094013 Hamada, N. (1981) Three-month Oral Toxicity Study in Rats: CGA- 41065 Technical: LBI Project No. 22102. Final
rept. (Unpub- lished study received Jan 28, 1982 under 100-EX-72; prepared by Litton Bionetics, Inc., submitted by
Ciba-Geigy Corp., Greens- boro, N.C.; CDL:246680-B; 246681)
00094016 Fletcher, D.W. (1981) Report to Ciba Geigy Corporation, Agricul- tural Division: Acute Oral Toxicity Study with
CGA-41065, Tech- nical in Bobwhite Quail: BLAL No. 81QD3. (Unpublished study received Jan 28, 1982 under 100-
EX-72; prepared by Bio-Life Associates, Ltd., submitted by Ciba-Geigy Corp., Greensboro, N.C.; CDL:246683-C)
00094038 Collins, P.F.; Tabor, D.G; Williams, S.C.; et al. (1982) Uptake, Balance and Characterization of (NO2)2-Phenyl-14C-
CGA-41065, Halo-Phenyl-14C-CGA-41065 and Metabolites in Greenhouse Grown Bright Tobacco, and the Balance
and Characterization of Their Radioactive Cigarette Smoke Products: M1-52-2P, 25: M1-52-4P, 45: Report No. ABR-
81056. (Unpublished study received Jan 28, 1982 under 100-EX-72; submitted by Ciba-Geigy Corp., Greensboro,
N.C.; CDL:246686-G)
00094039 Collins, P.F.; Tabor, D.G.; Williams, S.C.; et al. (1982) Uptake, Balance and Characterization of a 1:1 Mixture of
(NO2)2-Phenyl-14C-CGA-41065 and Halo-Phenyl-14C-CGA-4106 in Field Grown Bright Tobacco and the Balance
for Cigarette Smoke Products of This Tobacco: M1-52-6P, 6S: Report No. ABR-81057. (Unpublished study received
Jan 28, 1982 under 100-EX-72; submitted by Ciba-Geigy Corp., Greensboro, N.C.; CDL:246686-H)
45
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00094040 Collins, P.P.; Tabor, D.G.; Williams, S.C.; et al. (1982) Uptake, Balance and Characterization of Halo-Phenyl-14C-
CGA-4106 in Field Grown Bright Tobacco: M1-52-7P, 75: Report No. ABR-81060. (Unpublished study received Jan
28, 1982 under 100-EX-72; submitted by Ciba-Geigy Corp., Greensboro, N.C.; CDL: 246686-1)
00104250 Siglin, J.C.; Becci, P.J.; Parent, R.A. (1981) Primary Skin Irri- tation in Rabbits: FDRL Study No. 6818IAA.
(Unpublished study received Jan 28, 1982 under 100-EX-72; prepared by Food and Drug Research Laboratories, Inc.,
submitted by Ciba-Geigy Corp., Greensboro, N.C.; CDL:246679-D)
00116592 Ciba-Geigy Corp. (1982) CGA-41065-Tobacco: Report No. ABR-82059. (Compilation; unpublished study received
Oct4, 1982 under 100-640; CDL:248443-A)
00116594 Larson, E.; Matthews, R.; Naismith, R.; et al. (1982) 21 Day Dermal Toxicity Study in Rabbits: CGA-41065: Study
No. PH 430-CG-001- 81. (Unpublished study received Oct 4, 1982 under 100-640; prepared by Pharmakon Research
International, Inc., submitted by Ciba-Geigy Corp., Greensboro, NC; CDL:248444-B)
00116598 Forbis, A.; Franklin, L.; Boudreau, P.; et al. (1982) Early Life Stage Toxicity of CGA-41065 to Fathead Minnows
(Pimephales promelas, Rafinesque) in a Flow-through System: Report #29218. Final rept. (Unpublished study received
Oct 4, 1982 under 100- 640; prepared by Analytical Bio-Chemistry Laboratories, Inc., submitted by Ciba-Geigy Corp.,
Greensboro, NC; CDL:248445-B)
00116600 Forbis, A.; Boudreau, P.; Franklin, L.; et al. (1982) Chronic Toxicity of CGA-41065 to Daphnia magna under Flow-
through Test Conditions: ABC #28969. Final rept. (Unpublished study re- ceived Oct 4, 1982 under 100-640; prepared
by Analytical Bio- Chemistry Laboratories, Inc., submitted by Ciba-Geigy Corp., Greensboro, NC; CDL:248446-B)
00117622 Coate, W.; Fieser, S.; Hardy, R.; et al. (1982) Subacute Inhalation Study in Rats: CGA-41065 Treated Cigarettes:
Project No. 483- 216. Final rept. (Unpublished study received Nov 3, 1982 under 100-640; prepared by Hazleton
Laboratories America, Inc., sub- mitted by Ciba-Geigy Corp., Greensboro, NC; CDL:248737-C)
00145793 Science Applications, Inc. (19??) [Two-generation Reproduction Study with CGA-41065 Technical in Albino Rats]:
Addendum: Report No. CGA/SAI 281023. Unpublished study. 24 p.
46
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00149532 Holson, J. (1985) Two Generation Reproduction Study of CGA-41065 Technical in Albino Rats Volume I and II:
CGA/SAI 281023. Un- published study prepared by Science Applications, Inc. 587 p.
41670501 Collins, P. (1990) Uptake, Balance and Characterization of (NO2)2-phenyl-[carbon 14]-CGA-41065 and Halo-phenyl-
[carbon 14J-CGA-41065 in Greenhouse Bright Tobacco from Treated Soil and Their Fate in Soil: Flumetralin: Lab
Project Number: ABR/82042. Unpublished study prepared by CIBA-GEIGY Corp. 20 p.
41670502 Williams, S. (1990) Uptake, Balance and Characterization of (NO2)2-phenyl-[carbon 14]-CGA-41065 and Halo-
phenyl-[carbon 14J-CGA-41065 in Greenhouse Rotational Winter wheat, Soybeans, Carrots, Lettuce, and Corn: Lab
Project Number: ABR/82047. Unpublished study prepared by CIBA GEIGY Corp. 22 p.
41761507 Kirkland, R. (1991) CGA-41065 Technical: Acute Contact Toxicity of CGA-41065 to Honey Bees (Apis Mellifera L.):
Lab Project Number: CAR 198-90. Unpublished study prepared by California Agricultu- ral Research, Inc. 32 p.
41761508 Pluecken, U. (1991) CGA-41065: Hydrolysis of CGA-41065 (CGA-254567) under Laboratory Conditions: Lab Project
Number: 51/90: 90UP02. Unpublished study prepared by Ciba-Geigy Corp. 42 p.
41761509 Schaffer, A. (1991) CGA-41065: Aqueous Photolysis of CGA-41065 (CGA -254567) under Laboratory Conditions:
Lab Project Number: 49/90. Unpublished study prepared by Ciba-Geigy Ltd. 42 p.
41761510 Killer, A. (1991) CGA-41065: Soil Photolysis of CGA-41065 (CGA- 254567) under Laboratory Conditions: Lab
Project Number: 50/90. Unpblished study prepared by Ciba-Geigy Ltd. 42 p.
41761512 Abildt, U. (1991) CGA-41065: Adsorption/Desorption of CGA-41065 (CGA-254567) in Various Soil Types: Lab
Project Number: 52/90. Unpublished study prepared by Ciba-Geigy Ltd. 46 p.
41847001 Chetram, R. (1991) Tier 2 Seedling Emergence Nontarget Phytotoxi- city Study Using Prime + (CGA-41065): Lab
Project Nos. LR90-431; TX-90-0158. Unpublished study prepared by Pan-Agricultural Laboratories, Inc. 126 p.
42061601 Becci, P. (1986) CGA-41065 Technical: Lifetime Dietary Oncogenicity Study in Albino Mice: Lab Project Number:
7076-9. Unpublished study prepared by Food and Drug Research Labs., Inc. 3066 p.
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42061602 Tisdale, M. (1991) CGA-41065 Technical: Supplement to Lifetime Dietary Oncogenicity Study in Albino Mice: Lab
Project Number: 7076-9. Unpublished study prepared by Ciba-Geigy Corp. 18 p.
42061603 Keller, J. (1986) CGA-41065 Technical: Combined Chronic Toxicity/ Oncogenicity Study in Rats: Lab Project
Number: 22146. Unpub- blished study prepared by Litton Bionetics, Inc. 4194 p.
42061604 Tisdale, M. (1991) CGA-41065 Technical: Supplemental To: Combined Chronic Toxicity/ Oncogenicity Study in Rats:
Lab Project No: 22146. Unpublished study prepared by Ciba-Geigy Corp. 25 p.
42061605 Naismith, R. (1982) CGA-41065 Technical: Rat Hepatocyte Primary Culture/DNA Repair Test: Tests for Other
Genotoxic Effects: Lab Project Number: PH 311 -CG-001-81. Unpublished study prepared by Pharmakon Research
International, Inc. 27 p.
42566201a Kirkpatrick, D. (1992) Flumetralin: The Degradation of Flumetralin in Soil Under Aerobic, Anaerobic and Sterile
Conditions at 20 degrees Celsius: Lab Proj ect Number: 90JG01. Unpublished study prepared by Huntingdon Research
Center Ltd. 78 p.
42566201b Kirkpatrick, D. (1992) Flumetralin: The Degradation of Flumetralin in Soil Under Aerobic, Anaerobic and Sterile
Conditions at 20 degrees Celsius: Lab Proj ect Number: 90JG01. Unpublished study prepared by Huntingdon Research
Center Ltd. 78 p.
43014004 Craig, L. (1982) Supplement to: "Bioaccumulation , Depuration, and Metabolism of CGA-41065 in Bluegill Sunfish"
Part A (Bioaccumulation and Depuration) and Part B (Metabolism): (MRID 00117114): Lab Project Number: 698-1.
Unpublished study prepared by Analytical Development Corp. and Environmental Research and Technology, Inc. 39 p.
43014005 Kahrs, R. (1983) Uptake of (14Q-CGA-41065 in Field Rotational Soybeans, Carrots and Corn: Lab Project Number:
ABR-83019: M1-52-19PR: 19SR. Unpublished study prepared by Ciba-Geigy Corp. 23 p.
43456601 Bettencourt, M. (1994) CGA-41065: Acute Toxicity to Bluegill Sunfish (Lepomis macrochirus) Under Flow-Through
Conditions: Final Report: Lab Proj ect Number: 94/8/5428: 1781/0394/6438/ 105. Unpublished study prepared by
Springborn Labs, Inc. 75 p.
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43456602 Putt, A. (1994) CGA-41065: Acute Toxicity to Daphnids (Daphnia magna) Under Flow-Through Conditions: Lab
Project Number: 94/9/5487. Unpublished study prepared by Springborn Labs, Inc. 78 p.
43456603 Bettencourt, M. (1994) CGA-41065: Acute Toxicity to Sheepshead Minnow (Cyprinodon variegatus) Under Flow-
Through Conditions: Final Report: Lab Project Number: 94/9/5479: 1781/0394/6435/ 505. Unpublished study prepared
by Springborn Labs, Inc. 74 p.
43456604 Dionne, E. (1994) CGA-41065: Acute Toxicity to Eastern Oyster (Crassostrea virginica) under Flow-Through
Conditions: Final Report: Lab Project Number: 94/7/5391: 1781/0394/6436/504. Unpublished study prepared by
Springborn Labs, Inc. 81 p.
43456605 Bettencourt, M. (1994) CGA-41065: Acute Toxicity to Mysids (Mysidopsis bahia) Under Flow-Through Conditions:
Final Report: Lab Project Number: 94/10/5493: 1781/0394/6434/515. Unpublished study prepared by Springborn Labs,
Inc. 79 p.
43456606 Hoberg, J. (1994) CGA-41065: Toxicity to Duckweed (Lemna gibba): Final Report: Lab Project Number: 94/8/5425:
1781/0394/ 6437/410. Unpublished study prepared by Springborn Labs, Inc. 72 p.
43710702 Sheets, T.; Seltmann, H.; Yelverton, F. (1994) Residues of MH, flumetralin, and butralin on flue-cured tobacco.
Tobacco Science 38:25-29. 8 p.
43862801 Khalil, S. (1995) CGA-41065 Technical: Teratology Study in Rabbits: (Final Report): Lab Project Number: 931152:
TOX-1114C2MT. Unpublished study prepared by Ciba-Geigy Ltd. 309 p.
44565404 Glaza, S. (1998) Acute Dermal Toxicity Study of CGA-41065 15EC-Exp in Rabbits: Final Report: Lab Project
Number: 71005057: 277-97. Unpublished study prepared by Covance Labs., Inc. 20 p.
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V. APPENDIX E. LIST OF AVAILABLE RELATED DOCUMENTS AND ELECTRONICALLY AVAILABLE FORMS
Pesticide Registration Forms are available via the Agency's website at
Pesticide Registration Forms (These forms are in PDF format and require the Acrobat reader)
Instructions
1 . Print out and complete the forms. (Note: Form numbers that are bolded can be filled out on your computer then printed).
2. The completed form(s) should be submitted in hard copy in accord with the existing policy.
3. Mail the forms, along with any additional documents necessary to comply with EPA regulations covering your request, to the address below
for the Document Processing Desk.
DO NOT fax or e-mail any form containing 'Confidential Business Information' or 'Sensitive Information.'
If you have any problems accessing these forms, please contact Nicole Williams at (703) 308-555 1 or by e-mail at Williams. nicole&epa.gov.
The following Agency Pesticide Registration Forms are currently available via the Internet at the following locations:
8570-1
8570-4
8570-5
8570-17
8570-25
8570-27
8570-28
Application for Pesticide Registration/Amendment
Confidential Statement of Formula
Notice of Supplemental Registration of Distribution
of a Registered Pesticide Product
Application for an Experimental Use Permit
Application for/Notification of State Registration of a
Pesticide To Meet a Special Local Need
Formulator's Exemption Statement
Certification of Compliance with Data Gap
Procedures
httv.i
''ww\v. epa.sov'opprdOO l'forms'85 70- 1. pdf
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'wwv. epa.sov/opprdOO I /forms/8 5 70-4. pdf
tar.
•'www.epa.2ov/opprd001/fomis/8570-5.pdf
littv:/
'wwv. epa.sov/opprdOO 1 /forms/8 5 70- 1 7. pdf
tar.
•''www.eva.sov/ovvrd001/fornis/8570-25.vdf
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•''www.eva.sov/ovvrd001/fornis/8570-27.vdf
hllp://ww\v.epa.fi(n'/oppr{l001/fotms/8570-28.pcif
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8570-30
8570-32
8570-34
8570-35
8570-36
8570-37
Pesticide Registration Maintenance Fee Filing
Certification of Attempt to Enter into an Agreement
with other Registrants for Development of Data
Certification with Respect to Citations of Data (PR
Notice 98-5)
Data Matrix (PR Notice 98-5)
Summary of the Physical/Chemical Properties (PR
Notice 98-1)
Self-Certification Statement for the
Physical/Chemical Properties (PR Notice 98-1)
http://www.epa.2ov/opprd001/fomis/8570-30.txif
http://www.epa.gov/opprd001/fomis/8570-32.pdf
http:// 'www.epa.gov/oppijmsd I/PR Notices/pr98-5.pdf
http://www.epa.gov/opppmsdl/PR Notices/pr98-5.pdf
http:// 'www.epa.gov/oppijmsd I/PR Notices/pr98-l.pdf
http://www.epa.gov/opppmsdl/PR Notices/pr98-l.pdf
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VI. PESTICIDE REGISTRATION KIT
Dear Registrant:
For your convenience, we have assembled an online registration kit which contains the following pertinent forms and
information needed to register a pesticide product with the U.S. Environmental Protection Agency's Office of Pesticide Programs
(OPP):
1 . The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug and Cosmetic Act (FFDCA) as
Amended by the Food Quality Protection Act (FQPA) of 1996.
2. Pesticide Registration (PR) Notices
a. 83-3 Label Improvement Program- Storage and Disposal Statements
b. 84-1 Clarification of Label Improvement Program
c. 86-5 Standard Format for Data Submitted under FIFRA
d. 87-1 Label Improvement Program for Pesticides Applied through Irrigation Systems (Chemigation)
e. 87-6 Inert Ingredients in Pesticide Products Policy Statement
f. 90-1 Inert Ingredients in Pesticide Products; Revised Policy Statement
g. 95-2 Notifications, Non-notifications, and Minor Formulation Amendments
h. 98-1 Self Certification of Product Chemistry Data with Attachments (This document is in PDF format and requires the Acrobat
reader.)
Other PR Notices can be found at Mg.v/%n£}£1egaj^
3. Pesticide Product Registration Application Forms (These forms are in PDF format and will require the Acrobat reader).
a. EPA Form No. 8570-1, Application for Pesticide Registration/ Amendment
b. EPA Form No. 8570-4, Confidential Statement of Formula
c. EPA Form No. 8570-27, Formulator's Exemption Statement
d. EPA Form No. 8570-34, Certification with Respect to Citations of Data
e. EPA Form No. 8570-35, Data Matrix
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4. General Pesticide Information (Some of these forms are in PDF format and will require the Acrobat reader).
a. Registration Division Personnel Contact List
b. Biopesticides and Pollution Prevention Division (BPPD) Contacts
c. Antimicrobials Division Organizational Structure/Contact List
d. 53 F.R. 15952, Pesticide Registration Procedures; Pesticide Data Requirements (PDF format)
e. 40 CFR §156, Labeling Requirements for Pesticides and Devices (PDF format)
f. 40 CFR § 158, Data Requirements for Registration (PDF format)
g. 50 F.R. 48833, Disclosure of Reviews of Pesticide Data (November 27, 1985)
Before submitting your application for registration, you may wish to consult some additional sources of information. These include:
1. The Office of Pesticide Programs' website.
2. The booklet "General Information on Applying for Registration of Pesticides in the United States," PB92-221811, available
through the National Technical Information Service (NTIS) at the following address:
National Technical Information Service (NTIS)
5285 Port Royal Road
Springfield, VA 22161-0002
The telephone number for NTIS is (703) 605-6000.
3. The National Pesticide Information Retrieval System (NPIRS) of Purdue University's Center for Environmental and Regulatory
Information Systems. This service does charge a fee for subscriptions and custom searches. You can contact NPIRS by telephone
at (765) 494-6614 or through their website.
4. The National Pesticide Information Center (NPIC) can provide information on active ingredients, uses, toxicology and chemistry
of pesticides. You can contact NPIC by telephone at (800) 858-7378 or through their website at h(t]j:_//'ww_w._nci_s.orsLedi/_.
The Agency will return a notice of receipt of an application for registration or amended registration, experimental use permit, or
amendment to a petition if the applicant or petitioner encloses with his submission a stamped, self-addressed postcard. The postcard
must contain the following entries to be completed by OPP:
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• Date of receipt;
• EPA identifying number; and
• Product Manager assignment.
Other identifying information may be included by the applicant to link the acknowledgment of receipt to the specific application
submitted. EPA will stamp the date of receipt and provide the EPA identifying file symbol or petition number for the new submission.
The identifying number should be used whenever you contact the Agency concerning an application for registration, experimental use
permit, or tolerance petition.
To assist us in ensuring that all data you have submitted for the chemical are properly coded and assigned to your company, please
include a list of all synonyms, common and trade names, company experimental codes, and other names which identify the chemical
(including "blind" codes used when a sample was submitted for testing by commercial or academic facilities). Please provide a
chemical abstract system (CAS) number if one has been assigned.
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