United States Prevention, Pesticides EPA738-R-07-002
Environmental Protection And Toxic Substances March 2007
Agency (7508P)
f/EPA
Reregistration
Eligibility Decision
Aliphatic Esters
ListD
Case No. 4005
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Reregistration Eligibility Decision (RED) Document
for Aliphatic Esters
Approved by:
Debra Edwards, Ph. D.
Director
Special Review and Reregistration Division
Date:
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Table of Contents
Aliphatic Esters Reregi strati on Eligibility Decision Team 4
Glossary of Terms and Abbreviations 5
Summary 7
I. Introduction 7
II. Chemical Overview 7
III. Risk Assessment Summary 9
A. Human Health Risk Assessment 10
B. Ecological Risk Assessment 13
IV. Risk Management and Reregi strati on Decision 14
V. What Registrants Need to Do 16
Additional Generic Data Requirements 16
1. Additional Product-Specific Data Requirements 16
2. Labeling for End-Use Products 16
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Aliphatic Esters Reregistration Eligibility Decision Team
Office of Pesticide Programs:
Health Effects Risk Assessment
Elissa Reaves, Ph.D.
Shanna Recore
Yvonne Barnes
Alan Nielsen
Environmental Fate and Effects Risk Assessment
Mark Corbin
Colleen Flaherty
Registration Support
Jim Tompkins
Risk Management
Cathryn O'Connell
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 (referred to as the "EPA" or "the Agency")
has evaluated the risks from the supported uses of the aliphatic esters and has determined
that no unreasonable adverse effects will result from exposure to the methyl esters of
fatty acids, the only active ingredient in the aliphatic esters case with registered products.
Based on the lack of hazard concern, no quantitative human health risk assessment was
conducted. However, based on a potential concern of chemical pneumonia for handlers,
EPA will require the use of an organic-vapor respirator during mixing, loading, and
application of the product and will increase the restricted entry interval (REI) from 4
hours to 12 hours. Due to the limited use outside of greenhouses and the direct
application of this chemical to ornamentals in and around greenhouses no unreasonable
adverse ecological risks are expected and no ecological risk mitigation is required.
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. 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 decision regarding the reregi strati on eligibility
of the registered uses of the aliphatic esters. There are 6 active ingredients in the
aliphatic esters case; however, 5 of these active ingredients do not have active registered
products. These chemicals are not being supported and are not addressed in this
reregi strati on decision. The methyl esters of fatty acids (PC 079034) is the only active
ingredient in the case with an active product.
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 currently registered uses of
aliphatic esters are eligible for reregi strati on provided the mitigation and labeling
outlined in this RED are implemented.
II. Chemical Overview
There are 6 active ingredients in reregi strati on case 4005 for the aliphatic esters.
The active ingredients are presented below in Table 1. This RED evaluates only the
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active ingredients in this case with active products; therefore, only the methyl esters of
fatty acids (PC Code 079034) were assessed. The other 5 active ingredients in this case
have no product registrations and are not being supported for reregi strati on. These active
ingredients would be evaluated only if and when new registration applications were to be
submitted for new products.
The first product with methyl esters of fatty acids was registered in January 1968
to the Procter and Gamble Company (EPA Reg # 3573-23). The registration was
transferred to the Buckeye Cellulose Corporation in March 1979 (EPA Reg # 42855-1).
In March of 1987 the registration was transferred again to Cochran Corporation (EPA
Reg # 57582-1). The Cochran Corporation remains the only active registrant. Currently
only one active product is registered in this case, Off-Shoot-O (EPA Reg # 57582-1).
Table 1. Active ingredients in case 4005
Active Ingredient Name
methyl esters of fatty acids
amyl acetate
ethyl acetate
dibutyl succinate
1-tetradecanol formate
n-pentyl valerate
PC Code
079034
000169
044003
077802
079069
100901
CAS
67762-39-4
628-63-7
141-78-6
141-03-7
5451-63-8
2173-56-0
Status
1 active product (EPA Reg # 57582-1)
No active products.
No active products.
No active products.
No active products.
No active products.
The chemical structure and properties are presented below in Tables 2 and 3.
Table 2. Nomenclature for Methyl Esters of Fatty Acids
Chemical structure
Common name
Molecular formula
Molecular weight
IUPAC name (Estimation)
CAS name
CAS number
PC Code
O — CH3
CH3
Aliphatic Esters, Fatty Acids Methyl Esters (FAME)
CH3(CH2)nCOOCH3
158.24
(C6-C12) Alky Icarboxy lie acid methyl ester
Methyl ester, aliphatic
67762 - 39 - 4
079034
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Table 3. Physicochemical Properties of Methyl Esters of Fatty Acids
Parameter
Melting point/range
pH at 20 °C
Density at20°C
Water solubility at 20 °C
Solvent solubility at 20 °C
Vapor pressure at 25° C
Dissociation constant, pKa
Octanol/water partition coefficient
UV/visible absorption spectrum
Value
-20 °C
4.7
7.23 Ibs/gal
Zero gm/100 ml
Ethanol - 100 gm/100 ml
Petroleum Ether - 100 gm/ 100 ml
Less than 1 mm Hg
Not Applicable, non-polar
Estimate Log P = 3. 3 2
Not provided
Reference
MRID 417855-01
MRID 417855-01
MRID 417855-01
MRID 417855-01
MRID 417855-01
MRID 417855-01
MRID 417855-01
EPI™ version 3. 12
Data Gap1
1 The UV/visible absorption spectrum data requirement only applies to technical products.
Use Profile
Type of Pesticide:
Summary of Use:
Plant Growth Regulator or Pinching Agent.
May be applied as a foliar spray inside or outside a greenhouse on
ornamentals such as azalea, cotoneaster, juniper, ligustrum,
rhamnus, and taxus (yew). Most applications are to azaleas inside
greenhouses.
The methyl esters of fatty acids are also registered with the Food
and Drug Administration (FDA) for use as a direct food additive
(21 CFR 172.225) and in animal feed (21 CFR 573.640).
Formulation Type: Emulsifiable concentrate.
Application Methods: Handgun sprayer, high pressure handwand and low pressure
handwand.
Usage: Approximately 9,000 pounds of active ingredient are sold per year.
III. Risk Assessment Summary
The following is a summary of EPA's human health and ecological risk findings
and conclusions for the methyl esters of fatty acids, as presented fully in the Health
Effects Division document, Aliphatic Esters: Human Health Chapter of the
Reregistration Eligibility Decision (RED) Document (E. Reaves, et. al.; 6/30/06,
D330299), and the Environmental Fate and Effects Division document, Revised
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Ecological Risk Assessment for Use in Methyl Esters of Fatty Acids in Greenhouses,
(Corbin, M. and Flaherty, C., 2/8/07, D336252).
A. Human Health Risk Assessment
Toxicology
The available data for the methyl esters of fatty acids are sufficient for hazard
assessment. Methyl esters of fatty acids are straight chain and saturated methyl esters of
caproic acid (hexanoic acid), caprylic acid (octanoic acid), capric acid (decanoic acid),
and lauric acid (dodecanoic acid). Since they are metabolized in a manner similar or
identical to other neutral fats which are understood by the Agency, no additional testing
is required to understand the metabolism of methyl esters of fatty acids.
Acute toxicity studies show that the methyl esters are slight skin and eye irritants
and not toxic from the oral route of exposure (see Table 4). The skin sensitization and
acute inhalation studies are considered unacceptable but provide useful information for
hazard assessment. The skin sensitization and acute inhalation studies were waived in
1995 because methyl esters of fatty acids metabolize in a similar manner to other neutral
fats that are well understood by the Agency. The acute inhalation study raises a concern
for chemical pneumonia for handlers especially when used in greenhouses.
A chromosome aberration (bone marrow) test in Chinese hamsters along with a
literature source was submitted. The bone marrow test was found to be unacceptable
because it did not meet the guideline requirements. However, based on the published
literature that indicates that the straight chain methyl esters of fatty acids are structurally
related and metabolized in a similar manner to other neutral fats with the production of
similar metabolic byproducts, further testing of methyl esters for their genotoxic
(mutagenic) effects was deemed unnecessary.
The FDA has approved the methyl esters of higher fatty acids as a food additive
when used in animal feed (21 CFR 573.640). Based on the safe history of food additive
use and the known metabolism of these compounds, there is no information to suggest a
carcinogenic potential of the methyl esters of fatty acids or a concern for toxicity from
the oral route of exposure; therefore, a cancer assessment is not needed and was not
performed.
Reproductive, developmental, and subchronic toxicity studies are not available.
However, based on the metabolism data, there is no information to suggest that the
methyl esters of fatty acids would be of toxicological concern or that they would warrant
additional animal testing. Based on the available data, there is no evidence to suggest
increased susceptibility in infants and children.
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Table 4: Toxicity Data for Methyl Esters of Fatty Acids
Guideline
No.
870.1100
81-1
870.1200
81-2
870.1300
81-3
870.1400
81-4
870.2500.
81-5
870.2600
81-6
870.5385
84-2
Study Type
Acute oral [rat]
Acute dermal
[rabbit]
Acute inhalation
[rat]
UNACCEPTABLE
Eye Irritation
[rabbit]
Acute dermal
irritation [rabbit]
Skin sensitization
UNACCEPTABLE
Bone Marrow
Chromosome
Aberration
PC
Code
079034
079034
079034
079034
079034
079034
079034
MRID
43334501
43334502
43334505
43334503
43334504
43334505
43334507
Results
Methyl Esters (99.6%)
LD50>5000 mg/kg
Methyl Esters (99.6%)
LD50>2000 mg/kg
Unacceptable but data waived.
New study would not add to
knowledge (Kocialski
Memorandum 7/5/95)
Methyl Esters (99.6%)
Slight Irritant. Redness and
discharge at 1 hour only. No
involvement of the cornea or
the iris at any time.
Methyl Esters (99.6%)
Slight irritant. Slight to well
defined erythema observed
thru 72 hours and 4 days.
Data Waived (Kocialski
Memorandum 7/5/95).
Original conclusion is that this
formulation is not a sensitizer.
Unacceptable/Nonguideline
Data Waived (Kocialski
Memorandum 7/5/95)
Toxicity
Category
IV
III
III
III
IV
NA
NA
Dietary Exposure and Risk
Based on the lack of hazard concern and the metabolic profile of the methyl esters
of fatty acids, toxicological endpoints have not been identified for risk assessment
purposes and there are no food uses; therefore, a quantitative dietary (food and water)
risk assessment is not necessary and was not performed.
Additionally, the methyl esters of fatty acids have no pesticide tolerances under
section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA) because their uses are
not likely to result in residues in food. Accordingly, these pesticides are not subject to
the aggregate risk assessment requirements in FFDCA section 408.
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Residential Exposure and Risk
Since the methyl esters of fatty acids are chemical pinching agents for use on
woody ornamentals in occupational settings, and there are no residential uses of methyl
esters of fatty acids, a residential exposure assessment is not needed and has not been
performed.
Aggregate Exposure and Risk
An aggregate exposure assessment considers the different pathways (food, water,
occupational, and residential) through which exposure to the methyl esters of fatty acids
may occur. An aggregate assessment for the methyl esters of fatty acids is not necessary
to assess risks to human health. This is based on the fact that there are no pesticide food
uses, there are no residential uses, there is low oral hazard concern from the safe history
of use with the FDA, and no endpoints were identified for acute or chronic exposures
through the dermal or inhalation routes of exposure.
Occupational Exposure and Risk
There is potential for exposure to occupational mixers, loaders, and applicators of
methyl esters of fatty acids formulations; however, based on the lack of hazard concern
and the metabolic profile of the methyl esters of fatty acids, toxicological endpoints have
not been identified for risk assessment purposes. Therefore, an occupational exposure
assessment has not been performed.
Available dermal studies (acute dermal toxicity and dermal irritation) indicate that
the methyl esters of fatty acids are of low systemic toxicity via the dermal route and are
only slightly irritating. Also, an acute inhalation study was submitted in response to the
Phase 4 Data Call-In. This study was reviewed and determined to be unacceptable
(Kocialski Memorandum, D207640, 7/5/95). However, the results of this acute
inhalation study raise the possibility of chemical pneumonitis to handlers, from exposure
to the methyl esters of fatty acids due to the high volatility of the active ingredient. The
vapor pressure is less than 1 millimeters of mercury at 25 degrees Celsius. Specifically,
the review indicates: "a concern with regard to the use of this product in greenhouses."
For the reduction of risk of pneumonitis from inhalation exposure, the memo
recommended that: a) the label require the use of an organic-vapor respirator during use
of the product or b) a new acute inhalation study be conducted over the same time period
and number of days as originally conducted by the registrant with histopathology
conducted on the lungs. As a result of this RED, labels must be amended to include
organic vapor respirators, unless new data demonstrate they are not needed.
Based on the hazard profile for dermal exposure to methyl esters of fatty acids, no
post-application dermal risk was assessed. For uses within the scope of the Worker
Protection Standard for Agricultural Pesticides (40 CFR 170), a restricted entry interval
(REI) must be established. The REI is based on the category assigned to the acute dermal
toxicity, skin irritation potential, and eye irritation potential of the active ingredient. For
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the one registered product containing methyl esters of fatty acids, Off-Shoot-O,
Registration No. 57582-1, the current REI is 4 hours. EPA permits registrants to reduce
the Worker Protection Standard (WPS) restricted entry intervals (REIs) from 12 to 4
hours for certain low risk pesticides. Considering evidence of chemical pneumonia from
the existing inhalation study, the Agency no longer concludes that the conditions
warranting a 4 hour REI exist. Therefore, a 12 hour REI is required unless and until a
new acute inhalation study is conducted over the same time period and number of days as
originally conducted by the registrant with histopathology conducted on the lungs.
For occupational uses of methyl esters of fatty acid-containing products, dermal,
eye and respiratory irritation effects are addressed through precautionary labeling
requirements for use of Personal Protective Equipment (PPE). For the one registration
for methyl esters of fatty acids, the PPE required on the label is long sleeved shirts, long
pants, and shoes plus socks. In addition, the label must require the use of an organic-
vapor respirator during application of the product to protect from chemical pneumonia
from inhalation exposure.
B. Ecological Risk Assessment
The Agency has considered the ecological risks associated with the use of methyl
esters of fatty acids. Ornamentals such as cotoneaster, juniper, ligustrum, rhamnus, and
taxus (yew) are included on the methyl esters of fatty acids label and could be grown
indside or outside of greenhouses. According to usage information azaleas grown inside
greenhouses are the primary application site. Up to 10% of the total amount, or roughly
1,000 pounds of active ingredient, were estimated to be applied to ornamentals outside of
greenhouses. A screening level (Tier I) risk assessment was completed to evaluate the
potential risk to aquatic and terrestrial organisms using an application rate calculated
from use information, label instructions, and adjusted to consider the directed spray
method of application to ornamentals inside and outside greenhouses (1.914 Ibs a.i./A).
The application rate was translated from a per plant rate into a per acre rate because this
is the format that the screening model requires.
Aquatic exposure modeling using GENEEC2 provided an acute peak l-in-10 year
estimated environmental concentration (EEC) of 42 |ig/l. Comparing the aquatic EEC of
42 jig/1 to the most sensitive acute toxicity endpoint available, the daphnid ECso of 1.7
mg a.i./L, yields a risk quotient (RQ) of 0.02, which is below the level of concern (LOG)
of 0.5 for aquatic species and also below the endangered species LOG of 0.05. From this
assessment, the acute risks to aquatic species are presumed to be minimal.
Terrestrial dietary exposures for methyl esters of fatty acids were estimated using
the Tier-1 model, T-REX Version 1.2.3. Assuming a single application of 1.914 Ibs
a.i./A, the upper-bound residues on food items, such as vegetation and insects, range from
approximately 29 to 459 ppm. Acute risks to mammals appear to be minimal, given the
rat acute oral LD50 is greater than 5000 mg/kg. No acute or chronic avian toxicity data
are available. Based on this screening level assessment acute risks to aquatic organisms
and terrestrial mammals are presumed to be minimal.
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IV. Risk Management and Reregistration Decision
The Agency has determined that the methyl esters of fatty acids are 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 of the methyl esters of fatty acids.
Summary of risk mitigation measures:
• Increase the REI from 4 to 12 hours.
• Add an organic-vapor respirator for all mixers, loaders, and applicators.
Human Health Risks
No dermal, oral, or inhalation endpoints of toxicological concern were identified
for methyl esters of fatty acids; therefore, no quantitative human health risk assessment
was performed. However, based on an acute inhalation toxicity study there is a potential
concern of chemical pneumonia for occupational handlers especially when used in
enclosed areas like greenhouses. To reduce the potential risk of pneumonia from
inhalation exposure, EPA will require the use of an organic-vapor respirator during
mixing, loading, and application.
The current REI for methyl esters of fatty acids is 4 hours. Based on the concern
for chemical pneumonia, the REI will be increased to 12 hours unless and until
acceptable data as identified in this determination are submitted and support a lower REI.
Ecological Risks
From the screening level ecological risk assessment, the potential acute risks to
aquatic and terrestrial organisms assessed are below all levels of concern including
endangered species levels of concern. Based on the low toxicity for the species included
in the screening level assessment, the limited use of the methyl esters of fatty acids
outside of greenhouses, and the directed application of this chemical to ornamentals in
and around greenhouses, the acute and chronic risks to other aquatic and terrestrial
species not assessed are expected to be minimal.
There is no data to assess risk to birds, but based on data on other salts of fatty
acids that indicate that this group of compounds are practically non toxic to birds, and
that the methyl esters of fatty acids as approved flavoring agents in human food under 21
CFR 172 and can be used in animal feeds are per 21 CFR 573, no additional avian data is
required at this time. From the results of this screening level assessment, adverse
ecological effects are not expected and no ecological risk mitigation is required.
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Endangered Species
The Endangered Species Act required federal agencies to ensure that their actions
are not likely to jeopardize listed species or adversely modify designated critical habitat.
The Agency has developed the Endangered Species Protection Program to identify
pesticides whose use may cause adverse impacts on federally listed endangered and
threatened species, and to implement mitigation measures that address these impacts. To
assess the potential of registered pesticide uses that may affect any particular species,
EPA puts basic toxicity and exposure data developed for the REDs into context for
individual listed species and considers ecological parameters, pesticide use information,
the 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 recommended
in the RED being implemented at that time. A determination that there is a likelihood of
potential effects to a listed species may result in limitations on the use of the pesticide,
other measures to mitigate any potential effects, and/or consultations with the Fish and
Wildlife Service or National Marine Fisheries Service, as necessary. If the Agency
determines use of the methyl esters of fatty acids "may affect" listed species or their
designated critical habitat, EPA will employ the provisions in the Services regulations
(50 CFR Part 402).
Based upon the screening-level assessment conducted on the methyl esters of
fatty acids, the Agency has not definitively identified exceedences of endangered species
LOCs for direct effects to non-target animals or plants. Acute RQs did not exceed
endangered species LOCs for mammals, or freshwater fish and invertebrates. Acute
toxicity data were not available to assess potential risks to birds, aquatic or terrestrial
plants, or estuarine/marine fish and invertebrates, and chronic toxicity data were not
available for any taxon. The low acute risk to freshwater animals suggests that chronic
risk to freshwater animals from methyl esters of fatty acids may be unlikely. Similarly,
since risk to freshwater animals is likely to be minimal, the Agency does not anticipate
risk to estuarine/marine animals. Given the method of application and the minimal
outdoor use of methyl esters of fatty acids, risks to birds and non-target plants may be
minimal. Nevertheless, due to the lack of toxicity data, the Agency cannot preclude acute
risks to birds, aquatic and terrestrial plants, estuarine/marine fish and invertebrates, or
chronic risk to any taxon (i.e., freshwater animals, estuarine/marine animals, birds,
mammals).
The Agency considers a potential for not only direct effects, but also adverse
indirect effects to listed species that rely on other affected organisms. Because direct
effects to freshwater animals, estuarine marine animals, birds, mammals, and aquatic and
terrestrial plants cannot be precluded, indirect effects to listed species which rely on these
taxa can also not be dismissed.
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V. What Registrants Need to Do
The Agency has determined that the products containing methyl esters of fatty
acids (PC 079034) are eligible for reregi strati on provided that the mitigation measures
and label changes identified in this RED are implemented. Registrants will need to
amend their product labeling to incorporate the label statements set forth in the Label
Changes Summary Table 5. The Agency intends to issue a Data Call-In (DCI) requiring
product specific data. For product-specific data, the registrant will have eight months to
submit data and amended labels.
Manufacturing Use Products
Additional Generic Data Requirements
The generic database supporting the reregi strati on of the methyl esters of fatty
acids for the eligible uses has been reviewed and determined to be complete. No
additional data are required.
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 the pesticide after a determination of eligibility has been made.
The registrant must review previous data submissions to ensure that they meet current
EPA acceptance criteria and if not, commit to conduct new studies. If a registrant
believes that previously submitted data meet current testing standards, then the study
MRID numbers should be cited according to the instructions in the Requirement Status
and Registrants Response Form provided for each product. The Agency intends to issue a
product-specific data call-in (PDCI) outlining specific data requirements. For any
questions regarding the PDCI, please contact Karen Jones at (703) 308-8047.
2. Labeling for End-Use Products
To be eligible for reregi strati on, labeling changes are necessary to implement
measures outlined in Section IV above. Specific language to incorporate these changes is
specified in Table 5.
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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 5: Summary of Labeling Changes for the Methyl Esters of Fatty Acids
Description
Amended Labeling Language
Placement on Label
Manufacturing-Use Products
Required on all MUPs
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 group.
Environmental Hazards
Statements Required by
the RED and Agency
Label Policies
"Only for formulation into a plant growth regulator for the following use(s) [fill
blank only with those uses that are being supported by MP registrants]."
"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)."
"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 Pollutant 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. Do not contaminate water when
disposing of equipment wash-waters."
Directions for Use
Directions for Use
Directions for Use
End Use Products Intended for Occupational Use
PPE Requirements
Established by the RED1
for liquid (including
"Personal Protective Equipment (PPE)"
"All mixers, loaders, applications and other handlers must wear:
Immediately
following/below
Precautionary Statements:
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emulsifiable concentrate)
formulations
> Long-sleeved shirt and long pants,
> Shoes plus socks, and
> A NIOSH-approved respirator with
~ an organic-vapor removing cartridge with a prefilter approved for pesticides
(MSHA/NIOSH approval number prefix TC-23C), or
~ a canister approved for pesticides (MSHA/NIOSH approval number prefix TC-
14G), or
~ an organic-vapor cartridge or canister with any N*, R or P or He prefilter."
* Note to Registrant: Drop the "N" type prefilter from the respirator statement, if
the pesticide product contains, or is used with, oil.
Hazards to Humans and
Domestic Animals
User Safety
Requirements
"Follow manufacturer's instructions for cleaning/maintaining PPE. jf no sucn
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.)
Page 18 of 29
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* Remove the gloves statement if the end use product does not require gloves based
on the product acute toxicity tests.
Environmental Hazards
"Keep out of lakes, ponds, or streams. Do not contaminate water by cleaning of
equipment or disposal of wastes."
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
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.
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.
Page 19 of 29
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Appendices
Page 20 of 29
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Appendix A: Use Patterns Subject to Reregistration of Aliphatic Esters
Active ingredient
Methyl esters of
Fatty Acids
(PC 079034)
Commodity
Ornamentals:
azalea,
cotoneaster,
juniper,
ligustrum,
rhamnus, taxus
(yew)
Site
Inside and
outside
greenhouses
Application
Spray until the
growing tips
are covered.
Formulation
Emulsifiable
Concentrate
Application
Equipment
Handgun sprayers
High and Low
pressure
handwands
Directions for Use
Do not re -spray
plants; one spray
application per
pinch.
Do not re -spray
plants within 24
hours.
Page 21 of 29
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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 dodine case covered by this RED. It
contains generic data requirements that apply dodine 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
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.
Page 22 of 29
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Data Requirement
New
Guideline
Number
Old
Guideline
Number
Description
Use
Patterns
Citations
PRODUCT CHEMISTRY
830.1550
830.1600
830.1620
830.1670
830.1750
830.1800
830.7000
830.7200
830.7300
830.7370
830.7550
830.7840
830.7950
61-1
6 1-2 A
61-2B
61-2B
62-0
62-3
63-12
63-5
63-7
63-10
63-11
63-8
63-9
Product Identity and
Composition
Description of materials used to
produce the product
Description of production
process
Formation of Impurities
Certification of Limits
Analytical Method
pH
Melting Point
Density
Dissociation Constants in Water
Partition coefficient, shake flask
method
Solubility
Vapor Pressure
All
All
All
All
All
All
All
All
All
All
All
All
All
41785501
41785501
41785501
41785501
41785501
41785501
41785501
41785501
41785501
41785501
41785501
41785501
41785501
ECOLOGICAL EFFECTS
850.1075
850.1010
72-1A
72-2A
Fish Toxicity Bluegill
Freshwater Invertebrate Toxicity
A, B, D
A, B, D
43246701
43465501
TOXICOLOGY
870.1100
870.1200
870.1300
870.1400
870.2500
870.2600
870.5385
81-1
81-2
81-3
81-4
81-5
81-6
Acute Oral Toxicity - Rat
Acute Dermal Toxicity -
Rabbit/Rat
Acute Inhalation Toxicity - Rat
Primary Eye Irritation - Rabbit
Primary Skin Irritation
Dermal Sensitization
Mammalian Bone Marrow
Chromosomal Aberration Test
All
All
All
All
All
All
A, B, D
43334501
43334502
43334505
43334503
43334504
43334505
43334507
ENVIRONMENTAL FATE
835.4100
835.4300
162-1
162-4
Aerobic Soil Metabolism
Aerobic Aquatic Metabolism
A, B, D
A, B, D
42198001
42198001
Page 23 of 29
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Appendix C. Technical Support Documents
Additional documentation in support of this RED is maintained in the OPP
docket, EPA-HQ-OPP-2007-0235.
It is open Monday through Friday, excluding legal holidays, from 8:30 am to 4 pm.
All documents, in hard copy form, may be viewed in the OPP docket room or
downloaded or viewed via the Internet at the following site: www.epa.gov/pes1icides/reregistra1ion
These documents include:
HEP Document:
Aliphatic Esters: Human Health Chapter of the Reregi strati on Eligibility Decision (RED)
Document. Reaves, E., Recore, S., and Barnes, Y., D330299, 6/30/2006.
EFED Document:
Revised Ecological Risk Assessment for Use in Methyl Esters of Fatty Acids in
Greenhouses. Corbin, M., and Flaherty, C., D336252, 2/8/2007.
Page 24 of 29
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Appendix D. Citations Considered to be Part of the Data Base Supporting the
Reregistration Eligibility Decision
MRID Citation Reference
62728 Procter & Gamble (19??) Procter & Gamble Tobacco Sucker Control Agent No.
120. ?: Procter & Gamble. (Also~In~unpublished submission received Jun 4, 1968
under 3573-18; CDL:229498-A)
120754 Procter & Gamble Co. (1967) Technical Information Support for the Registration of
Off-Shoot-T Tobacco Sucker Control Agent. (Un- published study received Oct 3,
1967 under 3573-18; CDL: 007260-B)
120755 Procter & Gamble Co. (1967) ?Efficacy of Chemical Pruning Agents on Tobacco
and Other Crops). (Compilation; unpublished study received Oct 3, 1967 under
3573-23; CDL:007261-A)
120756 Procter & Gamble Co. (1967) Technical Information Support for the Registration of
Off-Shoot-O Chemical Pinching Agent for Ornamentals. (Unpublished study
received Oct 3, 1967 under 3573-23; CDL:007261-B)
120757 Conklin, E. (1967) First Quarterly Report on the Progress of the Experimental
Program for Off-Shoot, Chemical Pruning Agent for Ornamentals. (Unpublished
study received Oct 26, 1967 under 3573-23; submitted by Procter & Gamble Co.,
Cincinnati, OH; CDL:007262-A)
120758 Procter & Gamble Co. (1959?) Toxicity Data: ?Tobacco Sucker Control Agent No.
120|. (Unpublished study received Mar 7, 1967 under 3573-EX-l; CDL:127013-A)
120760 Procter & Gamble Co. (1967) ?Efficacy of Chemical Sucker Control Agents on
Tobacco). (Compilation; unpublished study received Mar 7, 1967 under 3573-EX-l;
CDL:127013-C)
41785500 Cochran Corp. (1991) Submission of Data To Support Reregistration of "Off-Shoot-
O," Chemical Pinching Agent for Ornamentals: Product Chemistry Study.
Transmittal of 1 study.
41785501 Hathaway, H. (1991) Reregistration of "Off-Shoot-O," Chemical Pinching Agent for
Ornamentals Active: Methyl esters of Fatty Acid (C6-C12). Unpublished study
prepared by Cochran Corp. 14 p.
42198000 Cochran Corp. (1992) Submission of environmental fate data in support of
reregistratration of Off-Shoot-O, chemical pinching agent for ornamentals.
Transmittal of 1 study.
42198001 Christensen, K. (1992) A Literature Review of Biodegradability and
Adsorption/Leachability of Fatty Acids and Fatty Acid Esters. Unpublished study
prepared by Springborn Labs., Inc. 13 p.
43185400 Cochran Corp. (1994) Submission of Product Chemistry Data for Off-Shoot-O in
Support of Reregistration. Transmittal of 1 study.
43185401 Hathaway, H. (1994) Octanol/Water Partition Coefficient Work to Upgrade MRID
41785501 Submission to Guideline Acceptability by Providing a Value in
Accordance with 45FR77350, 11-21-80: (Methyl Esters of Fatty Acids).
Unpublished study prepared by Cochran Corp. Lab. 5 p.
43246700 Cochran Corp. (1994) Submission of toxicology data in support of reregistration of
methyl esters of fatty acids. Transmittal of 1 study.
43246701 McGeehan, R.; Carlock, L. (1994) Methyl Esters of Fatty Acids: Freshwater Fish
Toxicity with Bluegill Sunfish, Lepomis macrochirus Rafmesque: Lab Project
Number: 11506/25/63. Unpublished study prepared by Union Carbide
Environmental Services Toxicity Lab. 25 p.
Page 25 of 29
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43334500 Cochran Corp. (1994) Submission of toxicity data in support of data call-in for
reregistration of Methyl Esters of Fatty Acids. Transmittal of 7 studies.
43334501 Jackson, D.; Ogilvie, S. (1994) Methyl Esters of Fatty Acids (C6-C12): Acute Oral
Toxicity (Limit) Test in Rats: Lab Project Number: 555719: 94017/COCH: 10481.
Unpublished study prepared by Inveresk Research International. 77 p.
43334502 Jackson, D.; Ogilvie, S. (1994) Methyl Esters of Fatty Acids (C6-C12): Acute
Dermal Toxicity (Limit) Test in Rabbits: Lab Project Number: 555703:
94018/COCH: 10482. Unpublished study prepared by Inveresk Research
International. 37 p.
43334503 Jackson, D.; Ogilvie, S. (1994) Methyl Esters of Fatty Acids (C6-C12): Primary Eye
Irritation Test in Rabbits: Lab Project Number: 555698: 94019/COCH: 10484.
Unpublished study prepared by Inveresk Research International. 39 p.
43334504 Jackson, D.; Ogilvie, S. (1994) Methyl Esters of Fatty Acids (C6-C12): Primary
Skin Irritation Test in Rabbits: Lab Project Number: 555682: 94020/COCH: 10483.
Unpublished study prepared by Inveresk Research International. 37 p.
43334505 McGeehan, R.; Kemman, R. (1994) Literature Review on Methyl Esters of Fatty
Acids. Unpublished study prepared by Compliance Services International. 180 p.
43334506 Palmer, S.; Beavers, J. (1994) Methyl Esters of Fatty Acids: An Acute Contact
Toxicity Study with the Honey Bee: Final Report: Lab Project Number: 392/101.
Unpublished study prepared by Wildlife International Ltd. 15 p.
43334507 Carlock, L.; McGeehan, R. (1994) Methyl Esters of Fatty Acids: Chromosome
Aberration (Bone Marrow) Test in Chinese Hamsters. Unpublished study prepared
by Compliance Services International. 19 p.
43465500 Cochran Corporation (1994) Submission of Toxicity Data in Support of the
Reregistration of Methyl Esters of Fatty Acids. Transmittal of 1 Study.
43465501 Davis, J.; Kernaghan, N. (1994) Methyl Esters of Fatty Acids: Acute Toxicity to the
Water Flea, Daphnia magna, Under Static Conditions: Lab Project Numbers:
J9402004B: 94016-COCH: J9402004A. Unpublished study prepared by Toxikon
Environmental Sciences. 89 p.
43474700 Cochran Corp. (1994) Submission of Hazard to Non-target Plants Data in Support of
Reregistration of Fatty Acids. Transmittal of 1 Study.
43474701 Kranzfelder, J. (1994) Methyl Esters of Fatty Acids ("Off-Shoot-O"): Seed
Germination/Seedling Emergence: Lab Project Number: J9402004C: 94021-COCH.
Unpublished study prepared by Toxikon Environmental Sciences. 108 p.
94029000 Cochran Corporation (1990) Reregistration Phase 3 Response: Methyl esters of fatty
acids (100% C8-C12).
94029999 Cochran Corporation (1990) Reregistration Phase 3 Response: Methyl esters of fatty
acids (100% C8 - C12). Correspondence and Supporting Material.
Page 26 of 29
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Appendix E. List of Available Related Documents and Electronically Available
Forms
Pesticide Registration Forms are available via the Agency's website at
http://www.epa. gov/opprdOOl/forms/.
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-
5551 or by e-mail at Williams.nicole(a),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
8570-30
8570-32
8570-34
8570-35
8570-36
8570-37
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
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.sov/opprd001/forms/8570-l.pdf
http://www. epa.sov/opprdOOl /forms/8 5 70-4. pdf
http://www.epa.sov/opprd001/forms/8570-5.pdf
http://www.epa.sov/opprd001/forms/8570-17.pdf
http://www. epa.sov/opprdOOl/forms/85 70-25.pdf
http://www.epa.sov/opprd001/forms/8570-27.pdf
http://www.epa.sov/opprd001/forms/8570-28.pdf
http://www.epa.sov/opprd001/forms/8570-30.pdf
http://www.epa.sov/opprd001/forms/8570-32.pdf
http://www. epa.sov/opppmsdl/PR Notices/pr98-5.pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-5.pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-l.pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-l.pdf
Page 27 of 29
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Pesticide Registration Kit http://www.epa.gov/pesticides/registrationkit/
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 http://www.epa.gov/opppmsdl/PRNotices
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
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:
Page 28 of 29
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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 http://www.nets.orst.edu.
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:
• 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.
Page 29 of 29
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