US Environmental Protection Agency
Office of Pesticide Programs
Reregistration Eligibility
Decision (RED) for Chlorflurenol
March 29, 2007
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United States Prevention, Pesticides EPA738-R-07-006
Environmental Protection and Toxic Substances 2007
Agency (7508P) OPP-2006-0874
Reregistration
Eligibility Decision for
Chlorflurenol Methyl
Ester
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Registration Eligibility Decision (RED) Document for
Chlorflurenol Methyl Ester
ListB
Case Number 2095
Approved by: L^M^^V ^ \Mn^^ ^1/2- Date: f Ifr/^-
Debra Edwards, Ph. D.
Director
Special Review and Reregistration Division
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TABLE OF CONTENTS
Chlorflurenol Team v
Glossary of Terms and Abbreviations vi
Abstract 1
I. Introduction 3
II. Chemical Overview 3
A. Regulatory History 4
B. Chemical Identification of Chlorflurenol 4
C. Use Sites 5
D. Formulations 6
E. Methods of Application 6
F. Use Rates 6
G. Annual Usage 6
H. Technical Registrant 6
III. Links to the Chlorflurenol Risk Assessments 6
IV. Risk Management and Reregistration Decision 7
A. Determination of Reregistration Eligibility 7
B. Public Comments and Responses 7
C. Regulatory Position 8
1. Regulatory Rationale 8
a. Human Health Risk Management 9
1). Drinking Water Risk Mitigation 9
2). Residential Postapplication Risk Mitigation.. 9
3). Occupational Handler Risk Mitigation 9
4). Occupational Postapplication Risk
Mitigation 10
b. Environmental Risk Management 10
2. Endocrine Disrupter Effects 11
3. Endangered Species Considerations 11
a. The Endangered Species Program 13
4. Other Labeling Requirements 13
V. What Registrants Need to Do 14
A. Manufacturing Use Products 14
1. Additional Generic Data Requirements 14
2. Labeling for Technical and Manufacturing Use Products... 15
B. End-Use Products 15
1. Additional Product-Specific Data Requirements 15
2. Labeling for End-Use Products 15
a. Label Changes Summary Table 16
VI. Appendices 25
iii
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Appendix A. Chlorflurenol Uses and Use-Patterns Eligible for
Reregistration 25
Appendix B. Table of Generic Data Requirements and Studies Used
to Make the Reregistration Decision for Clorflurenol 27
Appendix C. Technical Support Documents 31
Appendix D. Citations Considered Part of the Database Supporting
the Reregistration Decision (Bibliography) 33
Appendix E. Generic Data Call-In (GDCI) 40
Appendix F. Product-Specific Data Call-In (PDCI) 41
Appendix G. EPA'S Batching of Chlorflurenol Products for Meeting
Acute Toxicity Data Requirements for Reregistration 42
Appendix H. List of Registrants to be Sent this Data Call-in 43
Appendix I. List of Available Related Documents and Electronically
Available Forms 44
Appendix J: Chlorflurenol Human Health Risk Assessment 49
Appendix K: Chlorflurenol Ecological and Fate and Effects Assessment. 148
IV
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Chlorflurenol Reregistration Eligibility Decision Team
Risk Management
Tracy L. Perry
Eric Olson
Health Effects Risk Assessment
David Anderson
Yvonne Barnes
Shanna Recore
Environmental Fate and Effects Risk Assessment
Jennifer Leyhe
Shyilon (Larry) Liu
Ronald Parker
Biological and Economic Analysis Assessment
Sunil Ratnayake
John Faulkner
Jenna Carter
Registration Support
Juanita Gilchrist
Jim Tompkins
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Glossary of Terms and Abbreviations
ai Active Ingredient
aPAD Acute Population Adjusted Dose
CFR Code of Federal Regulations
cPAD Chronic Population Adjusted Dose
CSF Confidential Statement of Formulation
DCI Data Call-In
DEEM Dietary Exposure Evaluation Model
DFR Dislodgeable Foliar Residue
DNT Developmental Neurotoxicity
EC Emulsifiable Concentrate Formulation
ED WC Estimated Drinking Water Concentration
EEC Estimated Environmental Concentration
EPA Environmental Protection Agency
EUP End-Use Product
FDA Food and Drug Administration
FFDCA Federal Food, Drug, and Cosmetic Act
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FQPA Food Quality Protection Act
GLN Guideline Number
LC50 Median Lethal Concentration. A statistically derived concentration of a substance that
can be expected to cause death in 50% of test animals. It is usually expressed as the
weight of a substance per weight or volume of water, air, or feed, e.g., mg/1, mg/kg, or
ppm.
LD50 Median Lethal Dose. A statistically derived single dose that can be expected to cause
death in 50% of the test animals when administered by the route indicated (oral, dermal,
inhalation). It is expressed as a weight of substance per unit weight of animal, e.g.,
mg/kg.
LOC Level of Concern
LOAEL Lowest Observed Adverse Effect Level
ug/g Micrograms Per Gram
ug/L Micrograms Per Liter
mg/kg/day Milligram Per Kilogram Per Day
mg/L Milligram Per Liter
MOE Margin of Exposure
MRID Master Record Identification Number. EPA's system for recording and tracking studies
submitted.
MUP Manufacturing-Use Product
NOAEL No Observed Adverse Effect Level
OPP EPA Office of Pesticide Programs
OPPTS EPA Office of Prevention, Pesticides, and Toxic Substances
PAD Population Adjusted Dose
PHED Pesticide Handler's Exposure Data
PHI Pre-harvest Interval
ppb Parts Per Billion
PPE Personal Protective Equipment
ppm Parts Per Million
PRZM/EXAMS Tier II Surface Water Computer Model
RED Reregistration Eligibility Decision
REI Restricted Entry Interval
RfD Reference Dose
ROW Rights-of-way
RQ Risk Quotient
TGAI Technical Grade Active Ingredient
UV Ultraviolet
WPS Worker Protection Standard
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Abstract
This document presents the Environmental Protection Agency's (hereafter
referred to as EPA or the Agency) decision regarding the reregi strati on eligibility of the
registered uses of chlorflurenol methyl ester (hereafter referred to as chlorflurenol). The
Agency has determined that chlorflurenol-containing products are eligible for
reregi strati on provided that: (1) current data gaps are addressed; (2) the risk mitigation
measures identified in this document are adopted; and (3) labels are amended to
implement these measures.
Chlorflurenol is an herbicide and a plant growth regulator registered for use in
agricultural, commercial, and residential settings. As chlorflurenol has no food/feed uses
and no U.S. tolerances associated with its use, it is not subject to the Food Quality
Protection Act of 1996. The Agency has conducted human health and environmental fate
and ecological effect risk assessments for chlorflurenol. The risk conclusions of these
assessments are summarized below.
Overall Risk Summary
The Agency's human health assessment identifies potential chronic risks to
infants from the consumption of drinking water from groundwater sources containing
chlorflurenol residues. The reduction in turf rates and limit on number of applications
reduces chronic drinking water risks below the Agency's level of concern (LOG).
While potential residential handler risks for all use scenarios are below the LOG,
EPA's assessment identifies potential residential postapplication risks to adults and
toddlers (including dermal and incidental oral exposure to toddlers). However, the turf
mitigation measures lower these risks below the LOG.
Occupational handlers may be exposed to chlorflurenol while mixing, loading, or
applying chlorflurenol products. The Agency's assessment identifies potential
occupational handler risks for many use scenarios. In order to mitigate risks below the
Agency's LOG [margin of exposure (MOE) above 100], this RED requires reduced
application rates and the addition of a single layer of personal protective equipment
(PPE) plus gloves for all use patterns, with the exception of nonagricultural rights-of-way
(ROW), such as utility lines, fence/hedge rows, culverts, ditches, and median strips. In
order to mitigate potential risk to handlers for ROW scenarios, this RED requires that
handlers wear a double layer of PPE, plus gloves, when handling chlorflurenol for
nonagri cultural ROW applications.
EPA's assessment identifies potential risk to golf course workers through
exposure to postapplication residues of chlorflurenol. The required reduced application
rate for commercial use on turf (e.g., golf courses) reduces potential postapplication risks
to these workers below the LOG.
The Agency's ecological fate and effects assessment identifies potential chronic
risk to mammals from the use of chlorflurenol. However, the required reduced
application rates for turf, ROW, and forestry management areas lower the chronic
mammalian risk quotients (RQ) below the Agency's LOG; therefore, chronic risk to
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mammals (including listed species) is not expected.
While the Agency cannot determine definitive, acute RQ values for birds and
mammals, acute effects data demonstrate that chlorflurenol is practically nontoxic to
these taxa on an acute basis (avian LD50 >10,000 mg ai/kg body weight; mammalian
LD5o>5,000 mg ai/kg body weight). In addition, the required rate reductions for turf,
ROW, and forestry management areas result in a decrease in terrestrial estimated
environmental concentrations (EECs) to less than 500 ppm. As these EECs are below the
no-effect levels established at the highest doses tested for these taxa, the Agency does not
expect acute risk to birds and mammals (including listed species) from the use of
chlorflurenol.
The chlorflurenol database is insufficient to preclude risk to the following taxa:
birds (chronic), invertebrates, aquatic organisms, and nontarget plants. However, given
the current limited use patterns, the low volume of use, and the low acute toxicity to birds
and mammals, risk to these organisms is presumed to be low for nonlisted species. For
listed species of invertebrates, aquatic organisms, nontarget plants, and birds, the Agency
cannot preclude risk to these organisms given the lack of toxicity data.
As there is uncertainty in the ecological fate and effects assessment, the Agency is
calling in data to confirm that there is no unreasonable adverse effect to the environment
from the use of chlorflurenol. In addition, the Agency is requiring the registrant to place
a cap on the sale and distribution of chlorflurenol.
Risk Mitigation
To mitigate potential dietary, residential, and occupational risks from the use of
chlorflurenol and to reduce potential exposure to nontarget plants and animals, the
Agency is requiring and the registrant has agreed to:
• place a cap on the sale and distribution of chlorflurenol;
• prohibit the use on sod farms and greenhouses;
• prohibit aerial application;
• amend labeling for residential turf by lowering application rates from 3.0 Ibs ai/A
to 0.25 Ib ai/A and a maximum of two applications per year, with a minimum
application interval of 45 days;
• amend labeling for commercial use on turf (e.g., golf courses/parks/ornamental
turf/weed turf in ditches, etc.) by lowering the application rate from 3.0 Ibs ai/A to
0.5 Ib ai./A (liquid formulation) and 0.25 Ib ai./A (granular formulation), with a
limit of one application per year;
• amend labeling for nonagricultural ROW by lowering the application rate from
3.0 Ibs ai/A to 1.0 Ibs ai/A and one application per year;
• amend labeling for forestry management uses by lowering the application rate
from 4.0 Ibs ai/A to 2.0 Ibs ai/A, with a limit of one application per year;
• amend labeling for ornamental/shade trees uses by lowering the application rate
from 4.5 Ibs ai/A to 1.0 Ib ai/A, with a limit of one application per year; and,
• limit all uses, except for pineapples and residential turf, to one application per
year (number of applications currently unspecified on labels).
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Next Steps
The Agency is issuing this Reregi strati on Eligibility Decision (RED) document
for chlorflurenol as announced in a Notice of Availability published in the Federal
Register. In the future, EPA will issue a generic Data Call-In (DCI) for additional data
necessary to confirm the conclusions of this RED for the active ingredient chlorflurenol.
EPA will also issue a product specific DCI for data necessary to complete product
reregi strati on for products containing chlorflurenol.
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. The amended Act 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
submitted data by the EPA. 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 the 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 summarizes the Agency's revised human health and ecological
risk assessments and the reregi strati on eligibility decision for chlorflurenol. The
document consists of six sections. Section I contains the regulatory framework for
reregi strati on. Section II provides a profile of the use and usage of the chemical. Section
III provides links to the chlorflurenol human health and ecological risk assessments.
Section IV presents the Agency's reregi strati on eligibility and risk management
decisions. Section V summarizes label changes necessary to implement the risk
mitigation measures outlined in Section IV. Section VI provides information on how to
access related documents and contains the appendices that list related information and
supporting documents. The chlorflurenol risk assessments are available in the Public
Docket, under docket number EPA-HQ-OPP-2006-0874 on the web page,
http://www.regulations.gov.
II. Chemical Overview
Chlorflurenol is a plant growth regulator and an herbicide. As an herbicide,
chlorflurenol is used for the postemergent control of broadleaf weeds in turf. While
chlorflurenol has inherent herbicidal properties, it is typically combined with other
herbicides, such as dicamba, to enhance their activity. As a plant growth regulator,
chlorflurenol is used to retard the growth of grasses, broadleaf weeds, trees, shrubs, and
vines. It penetrates into herbaceous plants, via foliage and/or roots, and moves freely
inside the plant (aero and basipetal transport). Chlorflurenol blocks or slows down the
growth and development of growing tips and buds of herbaceous plants.
Chlorflurenol is also used to stimulate the growth of pineapple planting material
or sliplets. The Agency does not consider this use on pineapples to be a food use, as the
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first harvest from chlorflurenol-treated planting material occurs well over one year after
planting. Thus, no finite chlorflurenol residues are expected to remain at harvest and no
tolerance for pineapples is necessary.
A. Regulatory History
The first chlorflurenol registration was issued to the U.S. Borax Corporation by
the U.S. Department of Agriculture in 1970. In response to the 1989 GDCI, the
registrants, EM Industries and Shell International, decided to voluntarily cancel all
chlorflurenol registrations. Nita Industries, Inc. (subsequently Repar Corporation)
committed to support the reregistration of chlorflurenol through three end-use products.
The Pineapple Growers Association of Hawaii acquired a fourth end-use product, which
was eventually transferred to Repar Corporation in 1995.
In its 1991 Phase 2 reregistration response, Nita Industries, Inc. requested that the
Agency waive a number of data requirements due to the limited production of
chlorflurenol and to the "low volume/minor use" of the chemical. The registrant
provided the Agency with production and sales data for the principal chlorflurenol
product, and anticipated that future sales of the product would stay within a projected low
volume. As a result, the Agency waived or put in reserve several studies required in the
1989 GDCI.
B. Chemical Identification of Chlorflurenol
Chlorflurenol consists of three components. The major component (65% to70%)
is methyl 2-chloro-9-hydroxyfluorene-9-carboxylate (PC code 098801). The minor
components are methyl 2,7-dichloro-9-hydroxyfluorene-9-carboxylate (10% to 15%;
PC code 098803) and methyl 9-hydroxyfluorene-9-carboxylate (15% to 20%; PC code
098802). Since the chemical structures for the two minor components are very similar to
that of the major component, it is reasonable to believe that they all have herbicidal
activity. According to the registrant, these three components are inseparable and are
synthesized in a relatively constant ratio.
Tables 1 and 2 provide an overview of chlorflurenol's structure and properties.
Table 1. Nomenclature for Chlorflurenol
Chemical structure
Common name
Molecular formula
Major product
Structure:
0
CK>
chlorflurenol -methyl, flurenol
C15H11C1O3
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Molecular weight
IUPAC name
CAS name
CAS number
PC Code
274.07 g/mol
Methyl (JR,S)-2-chloro-9-hydroxyfluorene-9-carboxylate
Methyl 2-chloro-9-hydroxy-9//-fluorene-9-carboxylate
2536-31-4
098801
Table 2. Physicochemical Properties of Chlorflurenol
Parameter
Melting point/range
PH
Density
Water solubility
Solvent solubility at:
25 degrees Celsius
Vapor pressure
Dissociation constant, pKa
Octanol/water partition coefficient
UV/visible absorption spectrum
Value
136-142 degrees Celsius
Not Applicable, Crystalline material
-1.5 g/L
18mg/L
Cyclohexane 0.24 g/ 100 ml
Isopropanol 2.4 g/ 100 ml
Benzene 7. Og/1 00 ml
Ethanol 8. Og/1 00 ml
Methanol 1 5 g/ 100 ml
Acetone 26 g/ 100 ml
5 - 10"5 Torr at 25 degrees Celsius
None
Estimated Log P 2. 86
Estimate from fate data on water 65 or log P= 1.81
None provided
C. Use Sites:
Chlorflurenol is an herbicide and a plant growth regulator with no
registered food/feed uses. As an herbicide, it is registered for the
postemergent control of broadleaf weeds in turf. While Chlorflurenol has
inherent herbicidal properties, it is typically combined with other
herbicides, such as dicamba, to enhance their activity.
As a plant growth regulator, Chlorflurenol is used to retard growth of
grasses, broadleaf weeds, trees, shrubs and vines. It can be applied to
hedge and fence rows, ornamental turf, golf courses, recreational areas,
nonagricultural rights-of-way, and forestry management areas.
Chlorflurenol is also used as a plant growth regulator to produce pineapple
planting material (sliplets), which is the only agricultural use of this
herbicide. The Agency does not consider this use on pineapples to be a
food use, as the first harvest from Chlorflurenol-treated planting material
occurs well over one year after planting. Thus, no finite Chlorflurenol
residues are expected to remain at harvest and no tolerances in pineapples
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are necessary.
The only registered residential use of chlorflurenol is for the postemergent
control of broadleaf weeds on lawns.
• While chlorflurenol is registered for use on a variety of sites, it is currently
being marketed only for the control of pollen and fruit on ornamental
olives/citrus in Arizona, Nevada and California, and for the production of
pineapple planting material in Hawaii.
D. Formulations:
• Chlorflurenol is formulated as an emulsifiable concentrate and a granular.
E. Methods of Application:
• Chlorflurenol can be applied with several types of application equipment,
including airblast sprayers, ground boom sprayers, low pressure handwand
sprayers, handgun sprayers, rights-of-way sprayers, tractor-drawn
spreaders, push-type spreaders, and belly grinders.
F. Use rates:
• Application rates of chlorflurenol range from 0.25 pounds active
ingredient per acre on residential turf to 4.5 pounds active ingredient per
acre on ornamental/shade trees.
G. Annual usage:
As there is only one chlorflurenol registrant, annual usage data cannot be
disclosed for confidential business reasons. However, chlorflurenol is
considered a low volume use chemical.
H. Technical Registrant:
• Repar Corporation is the sole registrant.
III. Links to the Chlorflurenol Risk Assessments
For details on the risks associated with the use of chlorflurenol, please refer to the
Human Health and Ecological Risk Assessments for chlorflurenol located respectively in
Appendices J and K. These documents are also available in the public docket EPA-HQ-
OPP-2006-0874, located on-line in the Federal Docket Management System (FDMS) at
http://www.regulations.gov.
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IV. Risk Management and Reregistration Decision
A. Determination of Reregistration Eligibility
Section 4(g)(2)(A) of the Federal Insecticide, Fungicide and Rodenticide Act
(FIFRA) calls for the Agency to determine, after submission of relevant data concerning
an active ingredient, whether pesticides containing the active ingredient are eligible for
reregi strati on. The Agency has previously identified and required the submission of the
generic (i.e., active ingredient specific) data required to support reregistration of products
containing chlorflurenol.
The Agency has completed its assessment of the dietary (water), residential,
occupational, and ecological risks associated with the use of pesticides containing the
active ingredient chlorflurenol. Dietary (food) risks are not assessed because there are no
food/feed uses of chlorflurenol. Based on a review of the chlorflurenol data base and
public comments on the Agency's assessments for the active ingredient chlorflurenol, the
Agency has sufficient information on the human health and ecological effects of
chlorflurenol to make decisions as part of the reregistration process under FIFRA. The
Agency has determined that currently registered uses of chlorflurenol will not pose
unreasonable risks or adverse effects to humans or the environment provided that the risk
mitigation measures and label changes outlined in this RED are implemented; therefore,
products containing chlorflurenol are eligible for reregistration.
Products containing chlorflurenol are eligible for reregistration provided that:
(i) required generic and product-specific data are submitted; (ii) the risk mitigation
measures outlined in the document are adopted; and, (iii) label amendments are made to
implement these measures. Label changes are described in Section V of this document.
Appendix B identifies the generic data that the Agency reviewed as part of its
determination of reregistration eligibility of chlorflurenol and lists the submitted studies
that the Agency found acceptable.
Based on its evaluation of chlorflurenol, the Agency has determined that
chlorflurenol products, unless labeled and used as specified in this document, would
present risks inconsistent with FIFRA. Accordingly, should a registrant fail to implement
any of the risk mitigation measures identified in this document, the Agency may take
regulatory action to address the risk concerns from the use of chlorflurenol. If all
changes outlined in this document are incorporated into the product labels, then current
risks for chlorflurenol will be adequately mitigated for the purposes of this determination
under FIFRA. Once a comprehensive endangered species assessment is completed,
further changes to these registrations may be necessary.
B. Public Comments and Responses
The Agency solicited comments from the public regarding the reregistration of
chlorflurenol through a 60-day comment period, which opened on November 1, 2006 and
closed on January 2, 2007. During the public comment period, the Agency received
comments from Repar Corporation, the Maui Pineapple Company, Target Specialty
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Products, and several university researchers. The Maui Pineapple Company stated that
the loss of chlorflurenol, the only registered growth regulator for the production of
pineapple planting materials in Hawaii, will result in severe economic hardship for the
Hawaiian pineapple industry. Target Specialty Products attested to the important niche
that chlorflurenol plays in reducing the production of pollen and fruit in ornamental trees,
thus minimizing allergy-related effects and injuries from slipping on fallen fruit. Several
university researchers commented on chlorflurenol's ability to enhance the activity of
other herbicides, such as dicamba and picloram, when used at low rates in combination
with these herbicides. To view the complete set of public comments and the Agency's
responses to these comments, please refer to the public docket at
http://www.regulations.gov. EPA-HQ-OPP-2006-0874.
C. Regulatory Position
1. Regulatory Rationale
The Agency has determined that chlorflurenol is eligible for reregi strati on
provided the risk mitigation measures outlined in this document are adopted and label
amendments are made to reflect these measures. This decision considers the risk
assessments conducted by the Agency and the significance of the use of chlorflurenol.
To mitigate identified human health risk concerns from the use of chlorflurenol
and to reduce potential exposure to nontarget plants and animals, the Agency is requiring
and the registrant has agreed to:
• place a cap on the sale and distribution of chlorflurenol;
• prohibit the use on sod farms and greenhouses;
• prohibit aerial application;
• amend labeling for residential turf by lowering application rates from 3.0 Ibs ai/A
to 0.25 Ib ai/A and a maximum of two applications per year, with a minimum
application interval of 45 days;
• amend labeling for commercial use on turf (e.g., golf courses/parks/ornamental
turf) by lowering the application rate from 3.0 Ibs ai/A to 0.5 Ib ai/A (liquid
formulation) and from 1.1 Ibs ai/A to 0.25 Ib ai/A (granular formulation), with a
limit of one application per year;
• amend labeling for vegetation (e.g., weed turf, trees, vines and hedges) in
nonagricultural ROW and other difficult to access areas by lowering the
application rate from 3.0 Ibs ai/A to 1.0 Ib ai/A and one application per year;
• amend labeling for forestry management uses by lowering the application rate
from 4.0 Ibs ai/A to 2.0 Ibs ai/A, with a limit of one application per year;
• amend labeling for ornamental/shade trees uses by lowering the application rate
from 4.5 Ibs ai/A to 1.0 Ib ai/A, with a limit of one application per year; and,
• All limit all uses, except for pineapples and residential turf, to one application per
year (number of applications currently unspecified on labels).
The following is a summary of the rationale for managing risks associated with
the use of chlorflurenol. Where labeling revisions are warranted, specific language is set
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forth in the summary table in Section V of this document.
a. Human Health Risk Management
For additional details on the chlorflurenol human health risk assessment, please
refer to the Human Health Risk Assessments for chlorflurenol located in Appendix J.
This document is also available in the public docket EPA-HQ-OPP-2006-0874, located
on-line in the Federal Docket Management System (FDMS) at
http://www.regulations.gov.
1) Drinking Water Risk Mitigation
The Agency's human health assessment identifies potential chronic risks to
infants [142%-176% of the reference dose (RfD)] from the consumption of drinking
water from groundwater sources containing chlorflurenol residues. This potential risk is
based on eight applications (with 28 day intervals) to turf at 3 Ibs ai/A. To mitigate
potential drinking water risks, the Agency is requiring that the registrant reduce the turf
application rates from a maximum of 3.0 Ibs ai/A to 0.5 Ib ai/A for liquid formulations
and 0.25 Ib ai/A for granular formulations. In addition, chlorflurenol labels must specify
that only one application may be made per year (number of applications not currently
specified). These mitigation measures reduce chronic drinking water risks (3%-3.7% of
the RfD for infants) below the Agency's LOG (100% RfD).
2) Residential Postapplication Risk Mitigation
The Agency assessment considers several residential postapplication scenarios for
chlorflurenol, including dermal exposure from residue on lawns and turf (adult, youth and
toddler), hand-to-mouth transfer of residues on lawns (toddler), ingestion of pesticide
residue on treated grass (toddler), and incidental ingestion of soil from pesticide-treated
residential areas (toddler). Potential dermal risks to adults (MOE of 44) and toddlers
(MOE of 27) from high contact activity on lawns exceed the LOG (MOE of 100) at the 3
Ibs ai/A rate. Calculated combined risks to toddlers (i.e., dermal high contact activity
plus hand to mouth activity plus object to mouth activity on treated turf plus incidental
soil ingestion of pesticide residue from treated turf areas) are, therefore, also of concern.
To mitigate potential residential risks, the Agency is requiring that the registrant
lower the application rate for residential turf to 0.25 Ib ai/A, with a maximum of two
applications per year and 45 days between treatments. These measures reduce the
potential residential postapplication risks below the Agency's LOG.
3) Occupational Handler Risk Mitigation
Occupational handlers may be exposed to chlorflurenol while mixing, loading, or
applying chlorflurenol products. The Agency's assessment identifies potential
occupational handler risks for many use scenarios. In order to mitigate risks below the
LOG (MOE above 100), the Agency requires, through this RED, reduced application
rates for turf, forestry management, and ornamental/shade trees and the addition of a
single layer of personal protective equipment (PPE) plus gloves for these use patterns.
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For nonagricultural ROW, in addition to reduced application rates (from 3 Ibs ai/A to 1 Ib
ai/A), this RED requires that handlers wear a double layer of PPE, plus gloves, when
handling chlorflurenol. While the MOE for this ROW scenario (MOE=92) is slightly
below the target MOE (100), this potential risk is based on the very conservative
assumption that handlers absorb 100% of chlorflurenol residues through the dermal route.
Because of this conservative assumption, the Agency has determined that the potential
risk for the ROW scenario is below the LOG.
While the Registrant indicates that gymnosperm growth can be retarded at a rate
of 0.25 Ib ai/A, for sake of label simplicity, the Agency is requiring a maximum rate of
1.0 Ib ai/A for all vegetation (e.g., deciduous/evergreen trees, hedges, vines, turf) to be
controlled in ROW. The Agency does not expect the LOG to be exceeded for
chlorflurenol handlers at this rate, as the MOE at 0.25 Ib/A is 5,100 (with single layer
PPE plus gloves).
4) Occupational Postapplication Risk Mitigation
There are potential postapplication exposures to occupational workers during the
typical use patterns associated with chlorflurenol. EPA's assessment identifies potential
risk to golf course workers through postapplication exposure to chlorflurenol residues.
At the 3.0 Ibs ai/A rate for liquid and granular applications, risks are not a concern for
hand weeding and transplanting tasks at day 14 and for mowing at day 8. In order to
mitigate potential risk to golf course workers, the Agency is requiring that the turf rate be
reduced to 0.5 Ib ai/A for liquid applications and 0.25 Ib ai/A for granular applications.
These mitigation measures reduce the potential postapplication risks to golf course
workers below the Agency's LOG (MOE of greater than 100 on the day of application).
b. Environmental Risk Management
For additional details on the chlorflurenol ecological fate and effects risk
assessment, please refer to the Ecological Risk Assessment for chlorflurenol located in
Appendix K. This document is also available in the public docket EPA-HQ-OPP-2006-
0874, located on-line in the Federal Docket Management System (FDMS) at
http://www.regulations.gov.
Typical use of chlorflurenol may result in exposures to nontarget plants and
animals. The Agency's assessment identifies potential chronic risk to mammals from the
use of chlorflurenol. The risk quotients (RQs) range from 0.2 to 2.90, the upper bound
of which is above the target chronic LOG of 1.0. However, the reduced application rates
required in this reregi strati on decision lower the chronic mammalian risk quotients (RQs
from 0 to 0.83) below the LOG; therefore, chronic risk to mammals is not expected.
While the Agency cannot determine definitive, acute RQ values for birds and
mammals, acute effects data show that chlorflurenol is practically nontoxic to these taxa
on an acute basis (avian LD50 >10,000 mg ai/kg body weight; mammalian LD50>5,000
mg ai/kg body weight). In addition, the required rate reductions for turf (from 3.0 Ibs
ai/A to 0.5 Ib ai/A for liquid applications and 0.25 Ib ai/A for granular applications),
ROW (from 3.0 Ibs ai/A to 1 Ib ai/A), and forestry management areas (from 4.0 Ibs ai/A
10
-------
to 2.0 Ibs ai/A) result in a decrease in terrestrial estimated environmental concentrations
(EECs) to less than 500 ppm. As these EECs are below the no-effect levels established at
the highest doses tested for these taxa, the Agency does not expect acute risk to birds and
mammals from the use of chlorflurenol. The Agency also believes that potential chronic
risk to birds is unlikely due to the low acute toxicity to birds and mammals and the low
EECs.
The chlorflurenol database is insufficient to preclude risk to the following taxa:
birds (chronic), terrestrial invertebrates, aquatic organisms, and nontarget plants.
However, given the current limited use patterns, the low volume of use, and the low
toxicity to birds and mammals, risk to these organisms is presumed to be low. The
Agency is requiring a cap on the sale and distribution of chlorflurenol to maintain its low
volume use until additional data are submitted and reviewed by the Agency. These data
will be used to confirm the Agency's belief that there is no unreasonable adverse effect to
the environment from the use of chlorflurenol.
2. Endocrine Disrupter Effects
EPA is required under the FFDCA, as amended by FQPA, to develop a screening
program to determine whether certain substances (including all pesticide actives 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,
chlorflurenol may be subjected to additional screening and/or testing to better
characterize effects related to endocrine disruption.
3. Endangered Species Considerations
Based upon the screening-level assessment conducted for chlorflurenol, the
Agency has identified exceedances of endangered species LOCs for direct chronic effects
mammals. However, reduced application rates for turf, ROW, and forestry management
areas lower the chronic mammalian RQs below the LOG of 1.0 (RQs from 0 to 0.83);
therefore, chronic risk to listed mammals is not expected.
While definitive acute toxicity endpoints could not be determined for birds and
mammals, acute risk to listed birds and mammals is not expected as chlorflurenol is
considered to be practically nontoxic to these taxa on an acute basis. In addition, the rate
reductions required by this RED for turf, ROW, and forestry management areas result in
a decrease in terrestrial estimated environmental concentrations (EECs) to less than 500
ppm. As these EECs are below the no-effect levels established at the highest doses tested
for these taxa, the Agency does not expect acute risk to listed birds and mammals from
the use of chlorflurenol.
11
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The Agency believes that potential chronic risk to birds is unlikely due to the low
acute toxicity to birds and mammals and the low EECs. However, given the lack of
chronic toxicity data, the Agency cannot completely preclude chronic risk to listed birds
at this time.
The chlorflurenol database is insufficient to determine the potential acute/chronic
risk to the following listed taxa: nontarget plants, aquatic organisms, and invertebrates.
The Agency believes that potential risk to these taxa is unlikely given the current limited
use patterns, the low volume of use, and the low acute toxicity to birds and mammals.
However, given the lack of toxicity data, the Agency cannot preclude risk to these
organisms.
The Agency considers a potential for not only direct effects, but also adverse
indirect effects to listed species that rely on other affected organisms. There may be a
potential concern for indirect effects to the following groups of organisms from the use of
chlorflurenol: terrestrial plants, aquatic plants, birds, mammals, reptiles, aquatic
invertebrates, fish, amphibians, and terrestrial insects.
Table 3 summarizes the potential risk to listed species associated with the
application of chlorflurenol for turf use.
Table 3. Listed Species Risks Associated with Direct or Indirect Effects Due to
Applications of Chlorflurenol for Turf Use.
Listed Taxon
Terrestrial and semi-aquatic plants -
monocots
Terrestrial and semi-aquatic plants -
dicots
Insects
Birds
Terrestrial phase amphibians
Reptiles
Mammals
Aquatic vascular plants
Freshwater fish
Aquatic phase amphibians
Direct Effects
Yes"
Yesa
Yesa
Acute - No b; Chronic - Yes a
Acute - No b; Chronic - Yes a
Acute - No b; Chronic - Yes a
Acute - No b; Chronic - No c
Yesa
Yesa
Yesa
Indirect Effects
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
12
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Freshwater crustaceans
Mollusks
Marine/estuarine fish
Marine/estuarine crustaceans
Yesa
Yesa
Yesa
Yesa
Yes
Yes
Yes
Yes
a We cannot preclude risk due to lack of data.
b RQs were not calculated because toxicity endpoints were not definite values; however, since the amount estimated to
occur in the environment falls below 500 ppm, RQs will not likely exceed the LOG for endangered species.
c Based on calculations using a developmental study showing evidence of delayed skull ossification and cleft palates
in young rats.
a. The Endangered Species Program
The Endangered Species Act requires 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 threatened and endangered species,
and to implement mitigation measures that address these impacts. To analyze the
potential of registered pesticide uses that may affect any particular species, the Agency
uses basic toxicity and exposure data developed for the REDs and then 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, this species-specific analysis will also
consider the risk mitigation measures that are being implemented as a result of this RED.
Following this future species-specific analysis, a determination that there is a
likelihood of potential effects to a listed species may result in limitations on use of the
pesticide, other measures to mitigate any potential effects, or consultations with the Fish
and Wildlife Service and/or the National Marine Fisheries as appropriate. If the Agency
determines use of chlorflurenol "may affect" listed species or their designated critical
habitat, the Agency will employ the provisions in the Services' regulations (50 CFR Part
402). Until the species-specific analysis is completed, the risk mitigation measures being
implemented through this RED will reduce the likelihood that endangered and threatened
species may be exposed to chlorflurenol at levels of concern. The Agency is not
requiring specific chlorflurenol label language at the present time relative to threatened
and endangered species. If, in the future, specific measures are necessary for the
protection of listed species, the Agency will implement them through the Endangered
Species Program.
4. Other Labeling Requirements
In order to be eligible for reregi strati on, various use and safety information will be
included in the labeling of all end-use products containing chlorflurenol. For the specific
labeling statements and a list of outstanding data, refer to Section V of this document.
13
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V. What Registrants Need to Do
The Agency has determined that chlorflurenol is 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; however, additional data are
required to confirm this decision. In the near future, 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. Below are tables of additional generic data that the Agency intends to
require for chlorflurenol to be eligible for reregistration.
A. Manufacturing Use Products
1. Additional Generic Data Requirements
The generic database supporting the reregistration of chlorflurenol has been
reviewed and determined to be adequate for this reregistration assessment. However, the
following studies would reduce the uncertainty in the ecological risk assessment and will
be considered in the development of the generic DCI for chlorflurenol.
Table 5. Confirmatory Data Requirements for Reregistration
New
Guideline
Number
830.7050
835.2120
835.2240
835.2410
835.4100
835.4200
835.4400
835.1230
835.6100
850.1730
840.1100
840.1200
850.1075
850.1010
850.1035
850.1400
850.1300
850.1350
850.2300
Old Guideline
Number
none
161-1
161-2
161-3
162-1
162-2
162-3
163-1
164-1
165-4
201-1
202-1
72-1
72-2
72-3
72-4
71-4
Study/Requirements
UV/Visible Absorption
Hydrolysis
Aqueous photolysis
Soil photolysis
Aerobic soil metabolism
Anaerobic soil metabolism
Anaerobic aquatic metabolism
Adsorption/desorption
Terrestrial field dissipation
Fish bioaccumulation
Droplet size spectrum
Droplet Field Evaluation
Acute freshwater and estuarine/marine fish
Acute freshwater invertebrate
Acute estuarine/marine invertebrate
Chronic fish and invertebrate
Avian reproduction
14
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New
Guideline
Number
850.4225
850.4250
850.4400
850.5400
850.3020
Old Guideline
Number
123-1
123-2
141-1
Study/Requirements
Terrestrial plant seedling emergence and vegetative
vigor
Aquatic plant growth
Honey bee acute contact toxicity
2. Labeling for Technical and Manufacturing Use Products
To ensure compliance with FIFRA, technical and manufacturing use products
(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
should 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 6, 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 the pesticides 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 the Label Changes
Summary Table below.
15
-------
a. Label Changes Summary Table
In order to be eligible for reregi strati on, registrants must 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 6: Summary of Labeling Changes for Chlorflurenol
Description
Amended Labeling Language
Placement on Label
Manufacturing Use Products
For all Manufacturing
Use Products
"Only for formulation into a plant growth regulator or herbicide for the
following use(s) [fill blank only with those uses that are being supported
by MP registrant]."
"Not to be formulated into end-use products with directions for use on
sod farms."
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
16
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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
17
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End Use Products Intended for Occupational Use
PPE Requirements
Established by the
RED1
For Liquid
Formulations
"Personal Protective Equipment (PPE)"
"Some materials that are chemical-resistant to this product are"
(registrant inserts correct chemical-resistant material). "If you want
more options, follow the instructions for category" [registrant inserts
A,B,C,D,E,F,G,or H\ "on an EPA chemical-resistance category selection
chart."
"All mixers, loaders, applicators, and other handlers, except for rights-of-
way applicators, must wear:
long sleeve shirt, long pants,
shoes plus socks, and
chemical-resistant gloves."
"Rights-of-way applicators must wear:
coveralls over long-sleeved shirt and long pants,
chemical-resistant footwear plus socks,
chemical-resistant gloves, and
chemical-resistant headgear if overhead exposure."
Immediately following/below
Precautionary Statements: Hazards to
Humans and Domestic Animals
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.
18
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PPE Requirements
Established by the
RED2
For Granular
Formulations
"Personal Protective Equipment (PPE)"
"Some materials that are chemical-resistant to this product are"
(registrant inserts correct chemical-resistant material). "If you want
more options, follow the instructions for category" [registrant inserts
A,B,C,D,E,F,G,or H\ "on an EPA chemical-resistance category selection
chart."
"All loaders, applicators and other handlers must wear:
long sleeve shirt, long pants,
shoes plus socks, and
chemical-resistant gloves."
Immediately following/below
Precautionary Statements: Hazards to
Humans and Domestic Animals
User Safety
Requirements
"Follow manufacturer's instructions for cleaning/maintaining PPE. jf no
such instructions for washables exist, use detergent and hot water. Keep
and wash PPE separately from other laundry."
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.)
2 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.
19
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Environmental Hazards
"Do not apply directly to water, or to areas where surface water is present
or to intertidal areas below the mean high water mark. Do not
contaminate water when disposing of equipment washwater or rinsate."
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
Entry Restrictions for
products having
occupational uses on
the label not subject to
the WPS
Entry Restriction for non-WPS uses applied as a spray:
"Do not enter or allow others to enter the treated area until sprays have
dried."
Entry Restriction for non-WPS uses applied as a solid (i.e. granular)
and watered-in:
"Do not enter or allow others to enter the treated area until dusts have
settled."
If watering in is required, then add this statement:
"If soil incorporation is required after the application, do not enter or
allow others to enter the treated area (except those persons involved in
the incorporation) until the incorporation is complete. If the incorporation
is accomplished by watering-in, do not enter or allow others to enter the
treated area until the surface is dry after the watering-in."
If no WPS uses on the product label,
place the appropriate statement in the
Directions for Use Under General
Precautions and Restrictions. If the
product also contains WPS uses, then
create a Non-Agricultural Use
Requirements box as directed in PR
Notice 93-7 and place the appropriate
statement inside that box.
20
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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.
21
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Other Application
Restrictions for Liquid
Formulations
(Note: Except for tree
bark banding, the
maximum allowable
application rate and
maximum allowable
rate per year must be
listed as pounds or
gallons of formulated
product per acre, not
just as pounds active
ingredient per acre.)
"For Pineapple Plants (for production of planting material): maximum
application rate of 1 Ib ai/acre, maximum of two applications/year; a 2nd
application may only be made after an interval of 10 days."
"Not for use on sod farms."
"Aerial applications are prohibited."
"Not for use in greenhouses."
"For Turf (lawns, ornamental, golf courses, parks): maximum application
rate of 0.5 Ib ai/acre; one application per year."
"For Nonagricultural Rights-of-way (e.g., adjacent to highways, culverts,
ditches, under fences/utility lines, not to include residential use):
maximum application rate of 1 Ib ai/acre; one application per year."
"For Ornamental/Shade Trees: maximum application rate of 1 Ib ai/acre;
one application per year."
"For Tree bark banding: 0.083 Ib ai/gallon; one application per year."
"For Forestry management areas (e.g., conifer release,
forest/sheIterbelts): maximum application rate of 2.0 Ibs ai/acre; one
application per year."
Directions for Use
22
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Other Application
Restrictions for
Granular
Formulations
(Note: the maximum
allowable application
rate and maximum
allowable rate per year
must be listed as
pounds or gallons of
formulated product per
acre, not just as pounds
active ingredient per
acre.)
Turf (lawns): maximum application rate of 0.25 Ib ai/acre; one
application per year.
"Not for use on sod farms."
"Aerial applications are prohibited."
"Not for use in greenhouses."
Spray Drift
"Avoid spray drift (coarse sprays are less likely to drift)."
"Apply in a manner which confines spray to target area."
"Leave an adequate buffer zone between sensitive plants and spray
area."
Directions for Use
End Use Products Intended for Residential Use
Application
Restrictions
"Do not apply this product in a way that will contact any person, pet,
either directly or through drift. Keep people and pets out of the area
during application."
Directions for Use under General
Precautions and Restrictions
23
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Entry Restrictions
"Do not allow people or pets to enter the treated area until dusts have
settled. [If watering in is required after the application, do not enter or
allow others to enter the treated areas (except those involved in the
watering) until the watering-in is complete and the surface is dry.]"
Directions for use under General
Precautions and Restrictions
Environmental
Hazards
"Do not apply directly to water. Do not contaminate water when
disposing of equipment washwaters or rinsate."
Precautionary Statements immediately
following the User Safety
Recommendations
Other Application
Restrictions
(Note: the maximum
allowable application
rate and maximum
allowable rate per year
must be listed as
pounds or gallons of
formulated product per
acre, not just as pounds
active ingredient per
acre.)
Turf: lawns: maximum application rate of 0.25 Ib ai/acre; maximum 2
Directions for Use
applications per year; a
45 days.
->nd
application may be made after an interval of
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.
24
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VI. Appendices
Appendix A. Chlorflurenol Uses and Use-Patterns Eligible for Reregistration
Appendix A. Use Patterns Subject to Reregistration for Chlorflurenol
Application Timing
Application Type
Application Equipment
Formulation
EPA Reg.
No.
Maximum
Single
Application
Rate1
Maximum
No. of
Applications
per Year
Maximum
Seasonal
Rate
Application
Interval
(days)
Reentry
Interval
Limitations
Pineapples (for production of planting material, not a food use)
Forcing
Spray
Groundboom, Airblast
69361-6
HI-980007
1 Ib ai/A
2
2 Ibs ai/A
10 days
12 hours
Turf (lawns and ornamental turf, including golf courses and parks)
Foliar
Spray
Handgun, Low Pressure
Handwand,
Groundboom
Granular
Tractor-drawn spreader,
Push-type Spreader,
belly grinder
69361-1
69361-2
0.5 Ib ai/A
0.25 Ib ai/A
1
1
0 5 Ih
ai/A
0.25 Ib
ai/A
N/A
N/A
N/A
N/A
Turf (residential use on lawns)
Granular
Push-type spreader
Belly grinder
69361-3
0.25 Ib ai/A
2
0.5 Ib
ai/A
45 days
N/A
25
-------
Nonagricultural Rights-of-Way (e.g., adjacent to highways, culverts, ditches, under fences/utility lines, not to include
residential areas)
Foliar
Spray
Rights-of-way Sprayer
Handgun
Low-Pressure
Handwand
69361-6
l.Olbai/A
1
1 Ib ai/A
N/A
N/A
Forestry Management Areas (conifer release, forest/shelterbelt)
Spray
Low Pressure
Handwand
69361-6
2.0 Ib ai/A
1
2 Ib ai/A
N/A
N/A
Ornamental/Shade Trees
Foliar
Spray
Handgun, Low-Pressure
Handwand
69361-6
l.Olbai/A
1
1 Ib ai/A
N/A
N/A
Trees
Bark banding
Low-Pressure
Handwand
69361-6
0.083 Ib
ai/gallon
1
N/A
N/A
N/A
Maximum application rate identified from product label review.
26
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Appendix B. Table of Generic Data Requirements and Studies Used to Make the
Reregistration Decision for Chlorflurenol
Guide to Appendix B
Appendix B contains the list of data requirements which support the reregi strati on for active
ingredients within case #2095 (chlorflurenol) covered by this RED. It contains generic data
requirements that apply to chlorflurenol 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 Part 158. The reference numbers accompanying each test refer to
the test protocols set in the Pesticide Assessment Guidance, which are available from the
National Technical Information Service, 5285 Port Royal Road, Springfield, VA22161
(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 list the identify number of each study. This normally is the Master Record
Identification (MRID) number, but may be a "GS" number if no MRID number has been
assigned. Refer to the Bibliography appendix (Appendix D) for a complete citation of
the study.
27
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New Guideline
Number
Old Guideline
Number
Requirement
Use Pattern
Bibliographic Citation(s)
Product Chemistry
830.7000
830.7050
830.7200
830.7300
830.7370
830.7840
830.7950
63-12
N/A
63-5
63-7
63-10
63-8
63-9
PH
UV/Visible absorption
Melting point/melting range
Density
Dissociation Constants in Water
Water Solubility
Vapor Pressure
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
43154901
Data Gap
43154903
43154903
43154903
43154903
43154903
Environmental Fate
35.2120
835.2240
835.2410
835.4100
835.4300
835.4400
835.1240
835.6100
835.6300
850.1730
860.1400
835.2100
161-1
161-2
161-3
162-1
162-3
162-4
163-1
164-1
164-3
165-4
165-5
166-1
Hydrolysis
Photodegradation Water
Photodegradation Soil and Air
Aerobic Soil Metabolism
Anaerobic Aquatic Metabolism
Aerobic Aquatic Metabolism
Leaching/ Adsorption/Desorption
Terrestrial Field Dissipation
Forestry
Fish Bioaccumulation
Aquatic Non-Target Organism
Small Scale Prospective
Groundwater Study
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
43496201, Additional Data Required
Data Gap
Data Gap
43595403, Additional Data Required
Data Gap
Data Gap
43496202, Additional Data Required
Data Gap
Waived
Data Gap
Waived
Reserved
Spray Drift
840.1100
840.1200
201-1
202-1
Droplet Size Spectrum
Drift Field Evaluation
C,J,K
C,J,K
Data Gap
Data Gap
28
-------
Ecological Effects
850.2100
850.2200
850.2300
850.1075
850.1010
850.1045
850.1025
850.1035
850.1400
850.1400
850.1300
850.1350
850.1500
850.4225
850.4250
850.4400
850.5400
850.3020
850.3030
71-la
71-2
71-4
72-1
72-2
72-3a
72-3b
72-3c
72-4a
72-4a
72-4b
72-4c
72-5
123-la
123-lb
123-2
123-2
141-1
141-2
Avian Oral LD50 Quail/Duck
Avian Dietary LC50 Quail
Avian Reproduction
Freshwater Fish LC50
Freshwater Invertebrate LC50
Estuarine/Marine Fish LC50
Estuarine/Marine Mollusk EC50
Estuarine/Marine Shrimp EC50
Fish Early Life-Stage (freshwater)
Fish Early Life-Stage
(estuarine/marine)
Aquatic Invertebrate Life-Cycle
(freshwater)
Aquatic Invertebrate Life-Cycle
(estuarine/marine)
Fish Full Life-Cycle
Seedling Emergence (Tier II)
Vegetative Vigor (Tier II)
Aquatic Plant Growth (Tier II)
Algal Toxicity (Tiers I and II)
Honey Bee Acute Contact LD50
Honey Bee Residue on Foliage
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
43595401
43623601,43623602
Data Gap
120852/00047185, 140979, 45137401, 45242602, 45242601, 45137402,
90289, 119925/120889, 120870, Additional Data Required
45137403,45242603
Data Gap
Data Gap
Data Gap
Data Gap
Data Gap
Data Gap
Data Gap
Data Gap
Data Gap
Data Gap
Data Gap
Data Gap
Data Gap
Waived
Toxicology
870.1100
870.1200
870.1300
870.2400
870.2500
870.2600
870.3100
870.3100
870.3150
81-1
81-2
81-3
81-4
81-5
81-6
82-la
82-la
82- Ib
Acute Oral Toxicity Rat
Acute Dermal Toxicity Rabbit
Acute Inhalation Toxicity Rat
Primary Eye Irritation Rabbit
Primary Skin Irritation Rabbit
Dermal Sensitization Guinea pig
90-Day Oral Toxicity SD Rat
90-Day Oral Toxicity Wistar rat
90-Day Oral Toxicity Dog
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
43355402
43355403
45147201
43355404
43355405
43361701
45441001 [2001]
00120854 & 00120867 [1968]
00120868 [1968]
29
-------
870.3150
870.3700a
870.3700b
870.3800
870.4100a
870.4100b
870.4200b
870.4300a
870.5100
870-5300
870.5300
N/A
N/A
82- Ib
N/A
N/A
N/A
83-1
83-1
83-2
83-3a
N/A
N/A
84-2
N/A
N/A
21-Day Dermal Toxicity Rabbit
Developmental Toxicity SD Rat
Developmental Toxicity NZW
Rabbit
3 -Generation Reproduction
Charles River Rat
Chronic Toxicity Rat
Chronic Toxicity Dog
Carcinogenicity Mouse
Prenatal Developmental Toxicity
Study - Rat
Ames, S typhimurium
In vitro Cell (CHO) Chromosomal
Aberration
In vitro Mammalian Cell HGPRT
Test
Non GDL Metabolism &
Pharmacokinetics
Unacceptable/NG
Non GDL Carcinogenicity Rats
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
C,J,K
00120883 [1970]
4510901 [2000]
00120862 [1969]
00082867 [1973]
00082864 [1971]
00082863 [1975]
00082865 [1976]
45190901
43562802 [1995]
43562801 [1995]
45137405 [1988]
00082868 [1972]
0082866 [1969]
30
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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-2006-0874. 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.
The docket initially contained preliminary risk assessments, supporting documents, and
technical (or manufacturing-use) registrant error comments for chlorflurenol as of
November 1, 2006. After a sixty-day public comment period, EPA considered the public
comments that were submitted to the docket and revised the risk assessments as
necessary. The revised risk assessments, any supporting documents that needed to be
revised, and memos describing the Health Effects Division (HED), the Ecological Fate
and Effects Division (EFED), and the Biological and Economic Assessment Division
(BEAD) response to public comments will be added to the docket in April 2007.
The Agency documents in the docket include:
1. Federal Register Notice: Chlorflurenol Risk Assessment; Notice of
Availability, and Risk Reduction Options
2. Reader's Guide to the Chlorflurenol E-docket # EPA-HQ-OPP-
2006-0874
3. Request for Additional Information and Risk Management
Suggestions for the Reregi strati on of Chlorflurenol, Phase 3 Public
Comment Period (October 25, 2006)
4. Chlorflurenol Methyl Ester. HED Chapter of the Reregi strati on
Eligibility Decision Document (RED)
5. Chlorflurenol Methyl Ester: Occupational and Residential
Exposure Assessment for the Reregi strati on Eligibility Decision
Document
6. Response to Phase I comments from Mandava Associates (HED)
7. Chlorflurenol RED Chapter: Environmental fate and ecological
risk assessment for re-registration of chlorflurenol methyl ester
(ME), an herbicide/plant growth regulator for use on ornamentals,
hedge and fence rows, turf, shade trees, woody shrubs and vines,
and to produce planting material for pineapple production (EFED
memo)
-------
8. Environmental Fate and Ecological Risk Assessment for
Chlorflurenol Methyl Ester Reregi strati on
9. EFED RED Chapter Appendices
10. Water Assessment for Chlorflurenol Growth Regulator and
Herbicide
11. Review of Registrant Error Correction Comments on EFED
Reregi strati on Chapter for Chlorflurenol
12. Addendum to EFED RED Chapter for Chlorflurenol Methyl Ester
Accounting for Updated Label Rates
13. Revised Drinking Water Assessment for Chlorflurenol Growth
Regulator and Herbicide
14. Chlorflurenol: Human Health Risk Assessment Addendum for the
Reregistration Eligibility Decision Document
15. Chlorflurenol Methyl Ester: Chronic Drinking Water Exposure
and Risk Assessment for the Section 3 Reregi strati on Eligibility
Decision
16. Chlorflurenol: Revised Occupational and Residential Exposure
Assessment for the Reregi strati on Eligibility Decision Document
17. EFED's Responses to Phase 3 Comments for Chlorflurenol
18. Chlorflurenol: Response to comments from Maui Pineapple
Company, Ltd. (HED)
19. Response to Comments to Docket # EPA-HQ-2006-0874 during
the Phase 3 Comment Period for Chlorflurenol (BEAD)
32
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Appendix D. Citations Considered to be Part of the Database Supporting the
Reregistration Decision (Bibliography)
Guide to Appendix D
1. Contents of Bibliography. This bibliography contains citations of all studies
considered relevant by EPA in arriving at the positions and conclusions stated
elsewhere in the Reregistration Eligibility Document. Primary sources for studies
in this bibliography have been the body of data submitted to EPA and its
predecessor agencies in support of past regulatory decisions. Selections from
other sources including the published literature, in those instances where they
have been considered, are included.
2. Units of Entry. The unit of entry in this bibliography is called a "study." In the
case of published materials, this corresponds closely to an article. In the case of
unpublished materials submitted to the Agency, the Agency has sought to identify
documents at a level parallel to the published article from within the typically
larger volumes in which they were submitted. The resulting "studies" generally
have a distinct title (or at least a single subject), can stand alone for purposes of
review and can be described with a conventional bibliographic citation. The
Agency has also attempted to unite basic documents and commentaries upon
them, treating them as a single study.
3. Identification of Entry. The entries in this bibliography are sorted numerically by
Master Record Identifier, or "MRID" number. This number is unique to the
citation, and should be used whenever a specific reference is required. It is not
related to the six-digit "Accession Number" which has been used to identify
volumes of submitted studies (see paragraph 4(d)(4) below for further
explanation). In a few cases, entries added to the bibliography late in the review
may be preceded by a nine character temporary identifier. These entries are listed
after all MRID entries. This temporary identifying number is also to be used
whenever specific reference is needed.
4. Form of Entry. In addition to the Master Record Identifier (MRID), each entry
consists of a citation containing standard elements followed, in the case of
material submitted to EPA, by a description of the earliest known submission.
Bibliographic conventions used reflect the standard of the American National
Standards Institute (ANSI), expanded to provide for certain special needs.
a. Author. Whenever the author could confidently be
identified, the Agency has chosen to show a personal
author. When no individual was identified, the Agency
has shown an identifiable laboratory or testing facility as
the author. When no author or laboratory could be
identified, the Agency has shown the first submitter as the
author.
33
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b. Document date. The date of the study is taken directly
from the document. When the date is followed by a
question mark, the bibliographer has deduced the date
from the evidence contained in the document. When the
date appears as (1999), the Agency was unable to
determine or estimate the date of the document.
c. Title. In some cases, it has been necessary for the Agency
bibliographers to create or enhance a document title. Any
such editorial insertions are contained between square
brackets.
d. Trailing parentheses. For studies submitted to the Agency
in the past, the trailing parentheses include (in addition to
any self-explanatory text) the following elements
describing the earliest known submission:
(1) Submission date. The date of the earliest known
submission appears immediately following the
word "received."
(2) Administrative number. The next element
immediately following the word "under" is the
registration number, experimental use permit
number, petition number, or other administrative
number associated with the earliest known
submission.
(3) Submitter. The third element is the submitter.
When authorship is defaulted to the submitter, this
element is omitted.
(4) Volume Identification (Accession Numbers). The
final element in the trailing parentheses identifies
the EPA accession number of the volume in which
the original submission of the study appears. The
six-digit accession number follows the symbol
"CDL," which stands for "Company Data Library."
This accession number is in turn followed by an
alphabetic suffix which shows the relative position
of the study within the volume.
34
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Bibliography
MRID Studies Submitted to EPA
00082863 Frohberg, H.; Metallinos, A.; Pies, H.; et al. (1975) Chronic Toxicity Test
with IT 3456 in Beagle Dogs: Administration with the Food over a Period
of Two Years. (Translation; unpublished study received Apr 25, 1978
under 21137-EX-3; prepared by E. Merck, West Germany, submitted by
EM Laboratories, Inc., Elms- ford, N.Y.; CDL:097056-A).
00082865 Hofmann, A.; Weisse, G.; Kovac, W.; et al. (1976) IT 3456: 18-month
Carcinogenicity Study in Mice, Substance Administered in the Food:
Document No. CF 41 E/76. (Unpublished study received Apr 25, 1978
under 21137-EX-3; prepared by E. Merck, West Germany, submitted by
EM Laboratories, Inc., Elmsford, N.Y.; CDL: 097058-A)
00082868 Wenzl, H.; Garbe, A.; Nowak, H. (1972) EMD-IT 3294; EMD-IT 5733;
EMD-IT 3456: Investigations of the Kinetics and Distribution in Rats:
Document No. CF 6/72. (Translation; unpublished study received Apr 25,
1978 under 21137-EX-3; prepared by E. Merck, West Germany, submitted
by EM Laboratories, Inc., Elmsford, N.Y.; CDL:097058-E)
00120883 Kohn, F.; Stahoviak, E.; Vega, S.; et al. (1970) Report to United States
Borax Research Corporation: 21-day Subacute Dermal Toxicity Study of
Maintain CF-125: Lifestream Laboratories Project No. 1385.
(Unpublished study received Jan 7, 1970 under 1624-8; prepared by
Lifestream Corp., submitted by United States Borax & Chemical Corp.,
Los Angeles, CA; CDL:108523-A)
43154901 Mandava, N. (1994) Chlorflurenol Methyl Ester: Product Identity and
Composition. Unpublished study prepared by Science Regulatory Services
International. 50 p.
43154903 Mandava, N. (1994) Chlorflurenol Methyl Ester: Physical and Chemical
Characteristics. Unpublished study prepared by Science Regulatory
Services International. 7 p.
43355402 Wnorowski, G. (1994) Acute Oral Toxicity Limit Test: (Chlorflurenol
Methyl): Lab Project Number: 3170. Unpublished study prepared by
Product Safety Labs. 16 p.
35
-------
43355403 Wnorowski, G. (1994) Acute Dermal Toxicity Limit Test: (Chlorflurenol
Methyl): Lab Project Number: 2958. Unpublished study prepared by
Product Safety Labs. 15 p.
43355404 Wnorowski, G. (1994) Primary Eye Irritation: (Chlorflurenol Methyl): Lab
Project Number: 2605. Unpublished study prepared by Product Safety
Labs. 21 p.
43355405 Wnorowski, G. (1994) Primary Skin Irritation: (Chlorflurenol Methyl):
Lab Project Number: 2864. Unpublished study prepared by Product
Safety Labs. 16 p.
43361701 Wnorowski, G. (1994) Dermal Sensitization Test—Buehler Method:
(Chlorflurenol Methyl): Lab Project Number: 3035. Unpublished study
prepared by Product Safety Labs. 24 p. 43595402 Pant, K. (1995)
Evaluation of a Test Article in the Salmonella typhimurium Plate
Incorporation Mutation Assay in the Presence and Absence of
Aroclor-Induced Rat Liver S-9: Chlorflurenol-Methyl: Lab Project
Number: 0336-2110: CFM-NITA-842A. Unpublished study prepared by
SITEK Research Labs. 49 p.
43496201 Darskus, R. 1977. Hydrolysis of Chlorflurenol ME-methyl. Unpublished
study performed by CELAMERCK. Gmbh & Co. KG, Rhein, Germany,
compiled and submitted by SRS International Corporation, Washington,
DC, an agent for Nita Industries, Inc. Study No. CFM-NITA-1611.
43496202b Doebbler, G.F. 1981. Soil adsorption/desorption of Chlorflurenol ME-
methyl ester. Unpublished study performed by Union Carbide
Corporation Environmental Services, Tarrytown, NY; sponsored by EM
Industries, Inc., Elmsford, NY; and submitted by Nita Industries, Inc.,
(location not reported). Study Number CFM-NITA-1631. UCCES
Project No. 11507-86. EPA Case Number 2095. Active Ingredient
Number 98801.
43496202a Schluter, H. 1981. Leaching of 14C-chlorflurenol ME-methyl.
Unpublished study performed by Celamerck GmbH & Co. KG,
Ingelheim/Rhein, Germany and submitted by Nita Industries, Inc.,
(location not reported). Study Number CFM-NITA-1631. CM Document
No. 109AA-922-003. EPA Case Number 2095. Active Ingredient
Number 98801.
43562801 Thilagar, A. (1995) Test for Chemical Induction of Chromosome
Aberration in Cultured Chinese Hamster Ovary (CHO) Cells With and
Without Metabolic Activation: Final Report: Lab Project Number:
36
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0336-3110: CFM-NITA-842B. Unpublished study prepared by Sitek
Research Labs. 59 p.
43595401 Estop, C. and R. Teske. 1969. Acute Oral Toxicity of Chlorflurenol ME
Methyl Ester in Bobwhite Quail: Lab Project Number: CFM-NITA-711 A:
S-404. Unpublished study prepared by Hill Top Research, Inc. 29 p.
43595403 Sieper, H. 1969. Aerobic soil metabolism study. Unpublished study
performed by E. MERCK AG, Darmstadt, Germany, compiled and
submitted by SRS International Corporation, Washington, DC, an agent
for Nita Industries, Inc. Study No. CFM-NITA-1621.
43623601 Pedersen, C. and A. Solatycki. 1995. 8-Day Acute Dietary LC50 Study
with Chlorflurenol ME Methyl in Bobwhite Quail: Lab Project Number:
152-001-01. Unpublished study prepared by Bio-Life Associates, Inc. 48
P-
43623602 Pedersen, C. and A. Solatycki. 1995. 8-Day Acute Dietary LC50 Study
with Chlorflurenol ME Methyl in Mallard Ducklings: Lab Project
Number: 152-002-02. Unpublished study prepared by Bio-Life Associates,
Inc. 46 p.
45137404 Timm, A. (1988) Unscheduled DNA Synthesis in Hepatocytes of Male
Rates in Vitro (UDS Test) with Chlorflurenol-Methyl, Technical: Lab
Project Number: 117033. Unpublished study prepared by CCR Cytotest
Cell Research GmbH & Co. KG. 30 p. (OPPTS 870.5550}
45137405 Heidemann, A. (1988) Detection of Gene Mutations in Mammalian Cells
in Vitro HGPRT Test with Chlorflurenol-Methyl, Technical: Lab Project
Number: 117022. Unpublished study prepared by CCR Cytotest Cell
Research GmbH & Co. KG. 34 p. {OPPTS 870.5300}
45147201 Moore, G. (2000) Acute Inhalation Toxicity Study in Rats-Limit Test:
Chlorflurenol-Methyl (ICA-MECFOL): Lab Project Number: 9125: P330.
Unpublished study prepared by Product Safety Labs. 24 p. {OPPTS
870.1300}
45190901 Muller, W. (2000) Chlorflurenol-Methyl, Technical Oral (Gavage)
Teratogenicity Study in the Rat: Lab Project Number: 926-460-028:
460-028. Unpublished study prepared by Hazleton Laboratories
Deutschland GmbH. 222 p.
37
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45441001 Kuhn, J. (2001) 90-Day Oral Toxicity Study in Rats (Diet): Chlorflurenol
Methyl Ester: Final Report: Lab Project Number: 5472-99. Unpublished
study prepared by Stillmeadow, Inc. 136 p. (OPPTS 870.3100}
38
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Open Literature and Government Reports
Beyer, W. N.; Connor, E; Gerould, S. 1994. Survey of soil ingestion by wildlife. Journal of
Wildlife Management 58:375-382.
Fletcher, J.S., J.E. Nellesson and T. G. Pfleeger. 1994. Literature review and evaluation of the
EPA food-chain (Kenaga) nomogram, an instrument for estimating pesticide
residues on plants. Environ. Tox. And Chem. 13(9): 1383-1391.
Hoerger, F. and E.E. Kenaga. 1972. Pesticide residues on plants: correlation of representative
data as a basis for estimation of their magnitude in the environment. IN: F.
Coulston and F. Corte, eds., Environmental Quality and Safety: Chemistry,
Toxicology and Technology. Vol 1. George Theime Publishers, Stuttgart,
Germany, pp. 9-28.
Kirkwood, RC. 1983. The relationship of metabolism studies to the modes of action of
herbicides. Pestic. Sci. 14: 453-460.
Robinson, R. W., D. J. Cantliffe, and S. Shannon. 1971. Morphactin-induced parthenocarpy in
the cucumber. Science 171: 1251-1252.
Snyder, J. C., C. Carter, and D. E. Knavel. 1983. Chlorflurenol ME interrupts ovule
development of muskmelon. HortScience 18:345-347.
T-REX. 2005. Terrestrial Residue Exposure Model (T-REX), Version 1.2.3. August 8, 2005.
Environmental Fate and Effects Division, Office of Pesticide Programs, U.S.
Environmental Protection Agency, Washington, B.C.
U.S. EPA. 1993. U. S. Environmental Protection Agency. Wildlife Exposure Factors Handbook.
Volume I of II. EPA/600/R-93/187a. Office of Research and Development,
Washington, D. C. 20460.
U.S. EPA. 2001. U.S. Environmental Protection Agency. Ecological Risk Assessor Orientation
Package. U.S. Environmental Protection Agency, Ecological Fate and Effects
Division. Draft Version, August 2001.
U.S. EPA. 2004. U.S. Environmental Protection Agency. Overview of the Ecological Risk
Assessment Process in the Office of Pesticide Programs, U.S. Environmental
Protection Agency: Endangered and Threatened Species Effects Determinations.
Office of Prevention, Pesticide, and Toxic Substances. January 23.
Urban, D.J. and N.J. Cook. 1986. Hazard Evaluation Division Standard Evaluation Procedure
Ecological Risk Assessment. EPA 540/9-85-001. U.S. Environmental Protection
Agency, Office of Pesticide Programs, Washington, DC.
Willis and McDowell. 1987. Pesticide persistence on foliage. Environ. Contam. Toxicol. 100:23-
73.
39
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Appendix E. Generic Data Call-In (GDCI)
Note that a complete generic DCI, with all pertinent instructions, will be sent to
registrants under separate cover.
40
-------
Appendix F. Product-Specific Data Call-In (PDCI)
Note that a complete product-specific DCI, with all pertinent instructions, will be sent to
registrants under separate cover.
41
-------
Appendix G. EPA'S Batching of Chlorflurenol Products for Meeting Acute Toxicity
Data Requirements for Reregistration
The Agency has determined that no batching of chlorflurenol products is necessary given
the small number of registered products.
42
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Appendix H. List of Registrants to be Sent this Data Call-in
1) Repar Corporation
43
-------
Appendix I. List of Available Related Documents and Electronically Available
Forms
Pesticide Registration Forms are available at the following EPA internet site:
http://www.epa.gov/opprd001/fortns/.
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 hardcopy 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 following address for the Document
Processing Desk.:
Document Processing Desk (distribution code)*
Office of Pesticide Programs (7504P)
Environmental Protection Agency
1200 Pennsylvania Ave, NW
Washington, DC 20460-0001
* Distribution Codes are as follows:
(APPL) Application for product registration
(AMEND) Amendment to existing registration
(CAN) Voluntary Cancellation
(EUP) Experimental Use Permit
(DIST) Supplemental Distributor Registration
(SLN) Special Local Need
(NEWCO) Request for new company number
(NOTIF) Notification
(PETN) Petition for Tolerance
(XFER) Product Transfer
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@epamail.epa.gov. If you want these forms
mailed or faxed to you, please contact Lois White, white.lois@epa.gov or Floyd Gayles,
gayles.floyd@epa.gov.
44
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If you have any questions concerning how to complete these forms, please contact OPP's
ombudsperson for conventional pesticide products: Linda Arlington, (703) 305-5446
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 (in PR Notice 98-5)
Data Matrix (in PR Notice 98-5)
Summary of the Physical/Chemical
Properties (in PR Notice 98-1)
Self-Certification Statement for the
Physical/Chemical Properties (in PR
Notice 98-1)
http://www.epa.sov/opprd001/forms/8570-l.pdf
http://www.epa.sov/opprd001/forms/8570-4.pdf
http://www.epa.sov/opprd001/forms/8570-5.pdf
http://www.epa.sov/opprd001/forms/8570-17.pdf
http://www.epa.sov/opprd001/forms/8570-25.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
45
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Pesticide Registration Kit http://www.epa.gov/pesticides/registrationkit/
Dear Registrant:
For your convenience, we have assembled an on-line 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/PR_Notices.
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 Part 156, Labeling Requirements for Pesticides and Devices (PDF
format)
f. 40 CFR Part 158, Data Requirements for Registration (PDF format)
g. 50 F.R. 48833, Disclosure of Reviews of Pesticide Data (November 27,
1985)
46
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Before submitting your application for registration, you may wish to consult some
additional sources of information. These include:
1. The Office of Pesticide Programs' Web Site
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
The telephone number for NTIS is (703) 605-6000. Please note that EPA is
currently in the process of updating this booklet to reflect the changes in the
registration program resulting from the passage of the FQPA and the
reorganization of the Office of Pesticide Programs. We anticipate that this
publication will become available during the Fall of 1998.
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 Telecommunications Network (NPTN) can provide
information on active ingredients, uses, toxicology, and chemistry of pesticides.
You can contact NPTN by telephone at (800) 858-7378 or through their website:
http://npic.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
• 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.
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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
CAS number if one has been assigned.
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Appendix J: Chlorflurenol Human Health Risk Assessment
Date: July 10, 2006
MEMORANDUM
SUBJECT: Chlorflurenol Methyl Ester. HED Chapter of the Reregi strati on Eligibility
Decision Document (RED).
PC Code: 098801
Decision #: 362457
DP Barcode: D323832.
Risk Assessment Type: Single Chemical Aggregate
FROM: David G Anderson, Risk Assessor and Toxicologist
Shanna Recore, Occupational/Residential Risk Assessor
Yvonne Barnes, Product Chemist
Reregi strati on Branch II
Health Effects Division (7509P)
THROUGH: Alan Nielsen, Branch Senior Scientist
William Hazel, Chief
Reregi strati on Branch II
Health Effects Division (7509P)
TO: Tawanda Spears, Chemical Review Manager
Reregi strati on Branch III
Special Review and Reregi strati on Division
Attached is the HED risk assessment for Chlorflurenol methyl ester.
49
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Table of Contents
1.0 EXECUTIVE SUMMARY 53
2.0 Ingredient Profile 56
2.1 Summary of Registered/Proposed Uses 57
2.2 Registered Use Categories and Use Sites 57
2.3 Application Methods60
2.4 Structure and Nomenclature 60
2.5 Physical and Chemical Properties 61
3.0 Hazard/Dose-Response Characterization/Assessment 62
3.1 Hazard and Dose-Response Characterization 62
3.1.1 Database Summary: 62
3.1.2 Studies available and considered (animal, human, general
literature)
3.1.3 Mode of action, metabolism, toxicokinetic data 64
3.1.4 Sufficiency of studies/data 64
3.1.5 Toxicological Effects 64
3.1.6 Dose-response 64
3.2 Absorption, Distribution, Metabolism, Excretion (ADME) 65
3.3 FQPA Considerations 65
3.4 Hazard Identification and Toxicity Endpoint Selection 65
3.4.1 Acute Reference Dose (aRfD) - Females age 13-49, Children of
the General Population 65
3.4.3 Chronic Reference Dose (cRfD) 66
3.4.4 Incidental Oral Exposure (Short- and Intermediate-Term) 67
3.4.5 Dermal Absorption 68
3.4.6 Dermal Exposure (Short-, Intermediate- and Long-Term) 68
3.4.7 Inhalation Exposure (Short-, Intermediate- and Long-Term) 68
3.4.8 Level of Concern for Margin of Exposure 69
3.4.9 Recommendation for Combining Exposure Risk Assessments 69
3.4.10 Classification of Carcinogenic Potential 70
3.4.11 Mutagenicity Studies 70
3.4.12 Summary of Toxicological Doses and Endpoints for
chlorflurenol methyl ester for Use in Human Risk Assessments 70
4.0 Public Health and Pesticide Epidemiology Data 71
5.0 Dietary Exposure/Risk Characterization 71
5.1 Drinking Water Residue Profile 71
5.2 Food Residue Profile 74
6.0 Residential Exposure and Risks 74
6.1 Residential Handler Exposures and Non-cancer Risk Estimates74
6.1.1 Residential Handler Exposures and Risks 75
6.1.2 Handler Exposure Scenarios 75
6.1.3 Data and Assumptions for Handler Exposure Scenarios 76
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6.1.4 Residential Handler Exposure and Non-Cancer Risk Estimates 77
6.1.5 Residential Handler Exposure and Risk Estimates for Cancer 78
6.1.6 Summary of Risk Concerns and Data Gaps for Handlers 78
6.1.7 Recommendations for Refining Residential Handler Risk
Assessment
6.2 Residential Postapplication Exposures and Assumptions79
6.2.1 Residential Postapplication Exposure Scenarios 79
6.2.2 Data and Assumptions for Residential Postapplication
Exposure Scenarios 82
6.2.3 Residential Postapplication Exposure and Non-cancer Risk
Estimates
6.2.4 Residential Postapplication Exposure and Risk Estimates for
Cancer
6.2.5 Summary of Residential Postapplication Risk Concerns and
Data Gaps 91
6.2.6 Recommendations for Refining Residential Postapplication
Risk Assessments 91
6.3 Residential Risk Characterization 91
6.3.1 Characterization of Residential Handler Risks 91
6.3.2 Characterization of Residential Postapplication Risks 92
7.0 OCCUPATIONAL EXPOSURE AND RISKS 92
7.1 Occupational Handler Exposures and Risk Estimates 92
7.1.1 Data and Assumptions for Handler Exposure Scenarios 94
7.1.2 Occupational Handler Exposure Scenarios 102
7.1.3 Non-cancer Occupational Handler Exposure and Assessment 104
7.1.4 Cancer Occupational Handler Exposure and Risk Assessment 117
7.1.5 Summary of Risk Concerns and Data Gaps for Occupational
Handlers 118
7.1.6 Recommendations for Refining Occupational Handler Risk
Assessment 119
7.2 Occupational Postapplication Exposures and Non-Cancer Risk Estimates
119
7.2.1 Occupational Postapplication Exposure Scenarios 120
7.2.2 Data/Assumptions for Postapplication Exposure Scenarios 124
7.2.3 Occupational Postapplication Exposure and Non-cancer Risk
Estimates 124
7.2.4 Occupational Postapplication Exposure and Risk Estimates for
Cancer 127
7.2.5 Summary of Occupational Postapplication Risk Concerns and
Data Gaps 128
7.2.6 Recommendations for Refining Occupational Postapplication
Risk Assessment 128
8.0 Data Needs and Label Requirements 128
8.1 Toxicology 128
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8.2 Residue Chemistry 129
8.3 Occupational and Residential Exposure 129
References: 129
A.I Toxicology Data Requirements 130
A.2 Toxicity Profiles 131
A.3 Executive Summaries 135
A.3.1 Subchronic Toxicity 135
A.3.2 Prenatal Developmental Toxicity 137
A.3.3 Reproductive Toxicity 138
A.3.4 Chronic Toxicity 142
A.3.5 Carcinogenicity 143
A.3.6 Mutagenicity 144
A.3.7 Neurotoxicity 144
A.3.8 Metabolism 144
A.3.9 Dermal Absorption 145
A.4 References 145
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1.0 EXECUTIVE SUMMARY
This assessment provides the evidence for reregi strati on of chlorflurenol methyl
ester. The reregi strati on process provides re-review of previously registered pesticides
under the Federal Insecticide, Fungicide and Rodenticide Act [FIFRA] to assure scientific
reliability and conformity to the data standards established under the Food Quality
Protection Act [FQPA] of 1996.
Chlorflurenol methyl ester is a nonfood use herbicide, plant growth retardant and
plant growth regulator. As a herbicide and plant growth retardant it is used for the
postemergent control of annual grasses, broadleaf weeds, trees, shrubs and vines. As a
plant growth regulator, chlorflurenol is used to produce pineapple planting material
[sliplets] well over one year before the pineapples are harvested. As this use is not
expected to result in finite residues in pineapples, this is considered to be a nonfood use
and no tolerances are necessary in pineapples.
Chlorflurenol methyl ester [technical] is greater than 96% total ester and is
composed of three related chemicals chlorflurenol methyl ester [65% to70%],
dichlorflurenol methyl ester [10% to 15%] and deschlorflurenol methyl ester [15% to
20%].
Chlorflurenol methyl ester shows low acute toxicity by the oral, dermal and
inhalation routes [toxicity is category IV]. Clorflurenol methyl ester was essentially non-
irritating to the eye and skin, respectively [toxicity category III and IV]. It is not a skin
sensitizer in a Guinea pig study.
The acceptable and unacceptable studies with chlorflurenol methyl ester show no
severe toxicity. The most sensitive species is the dog showing slight red blood cell
destruction at 4 weeks after the start of the study and only at the highest dose tested. A
13-week subchronic study in rats showed toxicity, but did not confirm the hematological
effects. The female body weight decrement was seen in rats at higher dose levels than in
the dog study at month 13 or the effects on hematology at week 4. A 21-day dermal
study in rabbits with a formulation of chlorflurenol methyl ester showed no systemic
effects, but showed destruction of the hair follicles and edema in the treated skin. The
skin effects were dose related. These effects were considered due to skin irritation from
the formulation containing 87.5% inerts, most of which are known skin irritants.
Potential systemic effects of the technical grade could not be definitively evaluated due to
these inerts; however, systemic effects are not likely to be seen at lower dose levels than
those of the active ingredient tested in the 21-day dermal study in rabbits. Potential
reproductive effects were not tested in the 21-day dermal study.
A carcinogenicity study in mice showed no evidence of carcinogenicity at lower
doses or above a limit dose of 1 g/kg/day. A battery of mutagenicity studies was all
53
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negative.
Unacceptable kinetic/distribution studies suggest that each of the three
radiolabeled components comprising chlorflurenol methyl ester were barely detectable in
the rat mammary glands or in nursing pups. Since the studies used only one
female/treatment, the findings could not be verified. However, this study showed that
each of the three components in chlorflurenol methyl ester is probably rapidly excreted
mostly in the urine within 24 hours. Radiolabel in the mammary gland and the nursing
pups was not quantified in the treated animals.
Prenatal studies in the rat and rabbit show no increased fetal susceptibility. At the
highest dose tested, rats showed delayed ossification at higher incidence than control
incidence. Maternal toxicity in the form of body weight decrement was seen at mid- and
highest dose tested. The rabbit showed no effects in fetuses or mothers at the highest
dose tested. Post-natal studies were not required, but a 1973 three-generation
reproduction study previously submitted for other purposes showed equivocal litter size
and pup weight decrement at birth and subfertility in adult offspring, but showed a poor
dose response.
Due to these ambiguous findings in the reproduction study, an additional
uncertainty factor of 3X was used when calculating human oral risk. The additional 3X
factor may be removed by another acceptable reproduction study showing a more
definitive NOAEL for effects on the litters and fertility.
Exposures to the pesticide were calculated assuming maximum application rates
from both labels and from a March 14, 2006 memorandum from the Biological and
Economic Analysis Division [BEAD] of the USEPA [BEAD memo]. No dermal
absorption studies are available. This resulted in the assumption of 100% dermal
absorption from an oral study endpoint for dermal exposure.
When levels of exposure were above the Level of Concern [LOG], suggesting an
unacceptable exposure, the exposures to granular formulations were recalculated using
10% dermal absorption for comparison.
There is opportunity for adult residential handler exposure from the application to
lawns and ornamentals. A Margin of Exposure [MOE] less than 100 exceeds OPP's LOG
and suggests unacceptable risk. All residential handler activities showed MOE greater
than 100, suggesting acceptable risk. Attire for residential handlers is assumed to be
short-sleeved shirts, short pants, shoes and socks.
Several residential postapplication scenarios were identified for chlorflurenol
methyl ester, including dermal exposure from residue on lawns and turf (adult, youth and
toddler), hand-to-mouth transfer of residues on lawns (toddler), ingestion of pesticide
residue on treated grass (toddler), and incidental ingestion of soil from pesticide-treated
54
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residential areas (toddler).
For the adult populations, all postapplication risks were below HED's level of
concern, except for the 3.0 Ib ai/A (BEAD) application rates where MOEs are 44 on day
0. For the youth populations, all postapplication noncancer risks were below HED's
level of concern. For toddlers, postapplication noncancer risks are not of concern for the
oral route. For the dermal route, risks to toddlers from high contact activity on lawns
exceed HED's level of concern at the 1.0/1.1 Ib ai/A (Label) and 3.0 Ib ai/A (BEAD)
application rates, except when 10% dermal absorption is assumed for the granular
formulations. Calculated combined risks to toddlers (i.e., dermal high contact activity
plus hand to mouth activity plus object to mouth activity on treated turf plus incidental
soil ingestion of pesticide residue from treated turf areas) are therefore, also of concern,
except when 10 percent dermal absorption is assumed for the granular formulations.
There are potential exposures to occupational mixers, loaders, applicators, and
other handlers during the usual use-patterns associated with chlorflurenol methyl ester.
These risks were calculated assuming maximum application rates from both the product
labels and from the BEAD memo. For all occupational scenarios, the inhalation risks
were below HED's level of concern at the baseline level.
The dermal risks were below HED's level of concern at some level of mitigation
for all occupational scenarios, except applying liquid sprays using rights-of-way
equipment:
• to turf growing in culverts, rights of way, median strips, ditches, and/or under
security fences at the 3 Ib ai/A rate (Label & BEAD);
• to non-agricultural rights-of-ways/fence rows and hedge rows at the 3 Ib ai/A rate
(Label & BEAD);
• to gymnosperms and hardwoods at the 5 Ib ai/A rate;
• to shrubs, shade trees and vines at the 4.5 Ib ai/A rate (BEAD); and
• to high density forestry management at the 4.0 Ib ai/A rate (BEAD).
Risks remain a concern at maximum personal protective equipment and no engineering
controls are available for rights-of-way application equipment.
Using ORETF data, the dermal risks were a concern at baseline for handlers
mixing/loading/applying liquids with an overhead directed low pressure handwand
equipment for the scenarios where BEAD application rates are assessed. No ORETF data
currently are available to assess the corresponding personal protective equipment
exposures for these scenarios. However, using PHED data, the dermal risks were not a
concern with the addition of chemical-resistant gloves to baseline attire.
There are potential postapplication exposures to occupational workers during the
usual use-patterns associated with chlorflurenol. Specifically, there is concerned about
postapplication exposures from treatment of pineapples and golf course turf. In
agricultural crop settings, a Restricted Entry Interval or REI - is used to mitigate
55
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postapplication risks following applications to crops. The REI is time period following a
pesticide application during which entry into the treated area is restricted. To establish
REIs, EPA considers postapplication risks on varying days after application. For
pineapple applications, the MOEs are greater than 100 on day 0 (REI =12 hours) for all
of the exposure levels.
For the golf course turf using the 1.0 and 1.1 Ib ai/A (Label) rates for sprays and
granular applications respectively and assuming hand weeding and transplanting tasks are
performed and assuming 100% dermal absorption, risks are not a concern at day 4 for
liquid formulations and at day 5 for granular formulations. Assuming golf course
mowing tasks are performed, risks are not a concern on day 0 (12 hours following
application) for liquid or granular applications using these application rates and assuming
100 percent absorption. Risks are not a concern at day 0 (12 hours following application)
for granular applications for any postapplication tasks using the 1.1 Ib ai/A application
rate and assuming 10% dermal absorption.
For the golf course turf using the 3.0 Ib ai/A (BEAD) rates for sprays and granular
applications and assuming 100% dermal absorption, risks are not a concern for hand
weeding and transplanting tasks at day 14 and for mowing at day 8. For the golf course
turf using the 3.0 Ib ai/A (BEAD) rates for granular applications and assuming 10%
dermal absorption, risks are not a concern for any tasks at day 0 (REI = 12 hours).
See Sections 6.0 through 7.2.6 for Residential Exposure and Occupational Exposure
for mixed exposure scenarios of concern.
Potential contamination of surface water and ground water were modeled by Tier
IIPRZM/EXAMS and Tier I SCIGROW. Risk was assessed by DEEM for chronic
exposure to drinking water using modeled surface water estimated concentrations and
modeled groundwater estimated concentrations. Using surface water estimates,
exposures to all groups were below the chronic RfD and OPP's LOG. The highest
exposure groups were non-nursing infants at 20% of the chronic oral RfD and all infants
(< one year) at 16% of the chronic oral RfD. However, using ground water estimated
concentrations two groups were above the chronic RfD and above OPP's LOG. The
assessment by DEEM for ground water showed that the highest estimated exposure was
176% of the chronic RfD for non-nursing infants and 142% of the chronic RfD for all
infants (< 1 year). The next highest estimated exposure was to children 1-2 years at 64%
of the chronic RfD. These exposures were not combined with infants and children
exposured to lawns treated with sprays or granulated cholorflurenol. It should be noted
that since toddler exposure from treated lawns was above OPP's LOG, and any additional
exposure from drinking water would result in additional concern.
2.0 Ingredient Profile
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2.1 Summary of Registered/Proposed Uses
At this time, there are four products containing chlorflurenol that are intended for
occupational and/or residential uses. All products are registered by Repar Corporation.
Two of the products (Maintain CF 125 and Reap Thru Herbicide) are emulsifiable
concentrates and contain 12.5 and 15.9 percent active ingredient, respectively. Maintain
CF 125 is also registered as a special local needs product under EPA SLN No. HI-
980007. The other two products (Repar Broad Spectrum Weed and Feed and Repar
Weed and Feed 28-3-3) are granulars and contain 0.17 and 0.70 percent active ingredient,
respectively.
2.2 Registered Use Categories and Use Sites
An analysis of the current labeling and available use information was incomplete,
in that frequency of application and number of applications per season is not stated.
Chlorflurenol is registered for use in a variety of agricultural, commercial, and residential
scenarios and thus these populations are potentially exposed while performing handling
tasks, including mixing/loading, applying, and flagging tasks. It is also possible for these
populations to be exposed to chlorflurenol during postapplication time periods. Tables
la, Ib, and Ic provided the maximum application rates for the registered scenarios based
on information from the product labels. Table 2 provides the maximum application rates
from a March 14, 2006 memo from the Biological and Economic Analysis Division
(BEAD) of USEPA (BEAD memo).
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Table la: Summary of Maximum Application Rates for Registered Chlorflurenol Methyl
Ester Agricultural Uses - Label
Crop Site
Target of
Application
Maximum
Application
Rate
Application
Equipment
Area Treated or
Amount Handled Per
Day
Liquid Formulations
Pineapple plants:
for plant material
production (non
food use)
Plant growth
regulator
1 Ib a.i./A
(Label)
Groundboom
Airblast
80 acres
40 acres
Table Ib: Summary of Maximum Application Rates for Registered Chlorflurenol Methyl
Ester Commercial Uses - Label
Crop Site
Target of
Application
Maximum
Application
Rate
Application
Equipment
Area Treated or
Amount Handled Per
Day
Liquid Formulations
Turf: Lawns and
Ornamental Turf
(including golf
course and parks)
Gymnosperms
Hardwoods:
growing under
utility lines, as
screens or ground
cover, adjacent to
highways
Hedges:
growing under
Broadleaf
weeds and
plant growth
retardant
Plant growth
retardant
Plant growth
retardant
Plant growth
retardant
1.0 Ib a.i./A
0.25 Ib ai/100
gallons
1.0 Ib ai/100
gallons
1.0 Ib ai/100
gallons
low pressure
handwand
Handgun
Groundboom
low pressure
handwand
Handgun
rights-of-way sprayer
handgun
rights-of-way sprayer
low-pressure
handwand
handgun
rights-of-way sprayer
40 gallons
5 acres for A and
M/L/A
100 acres for M/L (for
20 LCOs)
40 acres
40 gallons
1,000 gallons
1,000 gallons
1,000 gallons
1,000 gallons
40 gallons
1,000 gallons
1,000 gallons
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Table Ib: Summary of Maximum Application Rates for Registered Chlorflurenol Methyl
Ester Commercial Uses - Label
Crop Site
utility lines, as
screen
Vines
growing under
utility lines, as
screens or ground
cover, rights-of-
way, hedgerows
Turf:
growing in culverts,
rights-of-way,
median strips,
ditches, under
security fences
Trees:
bark banding
Target of
Application
Plant growth
retardant
Plant growth
regulator
Plant growth
retardant
Maximum
Application
Rate
l.Olbai/lOOgal
3.0 Ib a. i. /acre
0.083 Ib a.i./gal
Application
Equipment
low-pressure
handwand
handgun
rights-of-way sprayer
low-pressure
handwand
rights-of-way sprayer
handgun
low-pressure
handwand
low-pressure
handwand
Area Treated or
Amount Handled Per
Day
40 gallons
1,000 gallons
1,000 gallons
40 gallons
80 acres
5 acres
5 acres
40 gallons
Granular Formulations
Turf: Lawns and
Ornamental Turf
(including golf
course and parks)
Broadleaf
weeds
1.1 Ib a. i. /acre
tractor-drawn
spreader
push-type spreader
belly grinder
40 acres
5 acres
1 acre
Table Ic: Summary of Maximum Application Rates for Registered Chlorflurenol
Methyl Ester Residential Uses - Label
Crop Site
Target of
Application
Maximum
Application
Rate
Application
Equipment
Area Treated or Amount
Handled Per Day
Granular Formulations
Turf:
lawns
Broadleaf
weeds
0.25 Ib a.i./A
push-type spreader
belly grinder
0.5 acre
1,000ft2
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Table 2. Summary of Maximum Application Rates for Registered Chlorflurenol
Methyl Ester Uses - BEAD
Use Site
Pineapple
Ornamental trees
Non-agricultural rights-of-
ways/fence rows and hedge rows
Established turf
High density forestry vegetation
management (plant density >1500
stems per acre; plant height > 8 ft)
Shrubs, shade trees and vines
Hardwood and gymnosperm trees
Treatment Type
Growth regulator
Growth regulator
Weed control &
growth retardant
Weed control & turf
growth retardant
Weed control
Growth regulator
Height control
Maximum Application Rate
(a.i. Ib/acre)
1.0
2.5
3 .0
3.0
4.0
4.5
5.0
2.3 Application Methods
Chlorflurenol is applied with several types of application equipment, including
airblast sprayers, ground boom sprayers, low pressure handwand sprayers, handgun
sprayers, rights-of-way sprayers, tractor-drawn spreaders, push-type spreaders, and belly
grinders. For information on the Occupational Handler assumptions and variables used
in the calculation of exposure, see [Section 7.1 Occupational Handler Exposures and
Risk Estimates].
2.4 Structure and Nomenclature
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Table 3. Nomenclature for Chlorflurenol Methyl Ester
Chemical structure
Major product
Structure:
n
Hydrolysis product
Common name
chlorflurenol-methyl, flurenol
Molecular formula
C15H11C1O3
Molecular weight
274.07 g/mol
IUPAC name
Methyl (RS)-2-chloro-9-hydroxyfluorene-9-carboxylate
CAS name
Methyl 2-chloro-9-hydroxy-9/-/-fluorene-9-carboxylate
CAS number
2536-31-4
PC Code
098801
2.5 Physical and Chemical Properties
Table 4 Physicochemical Properties of Chlorflurenol Methyl Ester
Parameter
Melting point/range
pH
Density
Water solubility
Solvent solubility at:
25 degrees Celsius
Value
136-142 degrees Celsius
Not Applicable, Crystalline material
-1.5
18mg/L
Cyclohexane 0.24 g/ 100 ml
Isopropanol 2.4 g/100 ml
Benzene 7.0 g/100 ml
Ethanol 8.0 g/100 ml
Methanol 15 g/100 ml
Acetone 26 g/100 ml
Reference
MRID 434549-03
MRID 43 154901
MRID 43 1549-03
MRID 43 1549-03
MRID 43 1549-02
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Table 4 Physicochemical Properties of Chlorflurenol Methyl Ester
Parameter
Vapor pressure
Dissociation constant, pKa
Octanol/water partition coefficient
UV/visible absorption spectrum
Value
5 - 10~5 Torr at 25 degrees Celsius
None
Estimated Log P 2.86
Estimate from fate data on water 65 or
log P= 1.81
None provided
Reference
MRID 43 1549-03
MRID 43 1549-03
MRID 433554-01
MRID 43496202
Data Gap
3.0 Hazard/Dose-Response Characterization/Assessment
3.1 Hazard and Dose-Response Characterization
3.1.1 Database Summary:
Chlorflurenol methyl ester shows low acute toxicity by the oral, dermal and
inhalation routes [toxicity is category IV]. Eye and skin irritation were mild and
essentially non-irritating, respectively [toxicity category III and IV]. It is not a skin
sensitizer in a Guinea pig study.
The acceptable and unacceptable studies with Chlorflurenol methyl ester show no
severe toxicity. The most sensitive species is the dog showing slight red blood cell
destruction at 4 weeks after the start of the study and only at the highest dose tested
[NOAEL/LOAEL = 31/94 mg/kg/day]. This red blood cell destruction was supported by
hemosiderin deposits in the liver at the 2-year termination. No studies were seen that
confirmed the hematological findings in the chronic dog study. At month 13, the study
showed decreased body weight in males and females, but not in females at termination.
An unacceptable 13 week study in 3 dogs/sex/group at comparable dose levels showed
inconsistent nominally decreased red blood cells, but no hemosiderin deposits at
termination. A 13-week subchronic study in rats showed a dose related decreased body
weight in females accompanied by decreased food efficiency and at the mid dose tested
and at the highest dose tested decreased male body weight gain . The female body
weight decrement was seen in rats at higher dose levels than in the dog study at month 13
or the effects on hematology at week 4. A 21-day dermal study in rabbits with a
formulation of Chlorflurenol methyl ester showed no systemic effects, but showed
destruction of the hair follicles and edema in the treated skin. The skin effects were dose
related. These effects were considered due to skin irritation from the formulation
containing 87.5% inerts, most of which are known skin irritants. Potential systemic
effects of the technical grade could not be definitively evaluated due to these inerts;
however, systemic effects are not likely to be seen at lower dose levels than those of the
active ingredient tested in the 21-day dermal study in rabbits. Potential reproductive
effects were not tested in the 21-day dermal study.
A carcinogenicity study in mice showed no evidence of carcinogenicity at lower
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doses or above a limit dose of 1 g/kg/day. A battery of mutagenicity studies was all
negative.
Unacceptable kinetic/distribution studies showed that each of the three
radiolabeled components comprising chlorflurenol methyl ester were barely detectable in
the rat mammary glands or in nursing pups. Since the studies used only one
female/treatment, the findings could not be verified. However, this study showed that
each of the three components in chlorflurenol methyl ester is probably rapidly excreted
mostly in the urine within 24 hours. Radiolabel in the mammary gland and the nursing
pups was not quantified.
Prenatal studies in the rat and rabbit show no increased fetal susceptibility. The
rat showed delayed ossification at higher incidence than control values. This delayed
ossification was shown at the highest dose tested and maternal toxicity was seen at the
mid- and highest dose tested. The rabbit showed no effects in fetuses or mothers at the
highest dose tested. Postnatal studies were not required, but a 1973 three-generation
reproduction study previously submitted for other purposes showed equivocal litter size
and pup weight decrement at birth and subfertility in adult offspring. The potential
effects were more variable than usual for a study on reproduction. The reproducibility of
these effects can be questioned. In addition, the study showed an excessive number of
pregnancies in female rats that showed no sperm during the period of cohabitation, i.e.,
no evidence that mating had occurred. Although, this finding could raise questions about
the conduct of the study, there was no suggestion in the data of a dose related response
among the generations of females that showed no sperm. However, when all these
females from all 6 groups of matings among the 3 generations in the study were added
together, there was a suggestion of a treatment related response. Due to these ambiguous
findings in the reproduction study, an additional uncertainty factor of 3X was used when
calculating human oral risk. The additional 3X factor may be removed by another
acceptable reproduction study showing a more definitive NOAEL for effects on the litters
and fertility.
3.1.2 Studies available and considered (animal, human, general literature)
No animal or human toxicity studies with chlorflurenol methyl ester were found
in the literature. The toxicity studies available and considered in the assessment of
chlorflurenol methyl ester were:
1. Acute - Oral LD50, Dermal LD50, Inhalation LC50, Eye and skin
irritation and dermal sensitization
2. Subchronic - An acceptable/nonguideline 21-day dermal study in rabbits. An
acceptable 90-day subchronic study in rats
3. Chronic - An acceptable chronic 2-year feeding study in dogs A
carcinogenicity study in mice.
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4. Developmental - An acceptable developmental toxicity study in rats and an
unacceptable developmental toxicity study in rabbits
5. Reproduction - An unacceptable 3-generation reproduction study in rats
6 Mutagenicity - A study on reverse mutation in S. typhimurium; A study on
chromosomal aberration in CHO cells; An in vitro study for rat
hepatocyte unscheduled DNA synthesis; An in vitro mammalian
cell HGPRT test. The battery of guideline mutagenicity studies
was acceptable.
7. Kinetics/distribution - An unacceptable/non-guideline study of kinetics and
distribution, including radiolabel in rat milk.
3.1.3 Mode of action, metabolism, toxicokinetic data
There was no data on a mode of action. However, general information about
suggested distribution and kinetic data has been submitted. The data suggest that
chlorflurenol methyl ester is circulated enterohepatically and excreted in the feces and
mostly in urine all within 24 hours, resulting in no accumulation.
3.1.4 Sufficiency of studies/data
The toxicity data base for chlorflurenol methyl ester is adequate for risk
assessment. The toxicity data requirements for a nonfood use pesticide depend on
exposure and toxicity. In the case of chlorflurenol methyl ester which shows both low
toxicity and moderate exposure, the requirements are the 6 acute studies, a subchronic
study, a developmental toxicity study and a battery of mutagenicity studies. These data
requirements have been satisfied by acceptable studies. However, a 1973 reproduction
study submitted for other purposes shows equivocal effects that add uncertainty to the
data base.
3.1.5 Toxicological Effects
Toxicological effects of concern are found in a chronic study in dogs at 4 weeks.
Chlorflurenol methyl ester administered to dogs resulted in treatment-related red blood
cell destruction at the highest dose tested within 4 weeks with a NOAEL/LOAEL of
31/94 mg/kg/day. No other study showed a lower NOAEL.
3.1.6 Dose-response
The acceptable and unacceptable subchronic studies in the rat and dog showed
treatment related effects at the highest dose tested [HDT] in the dog.. The chronic dog
study showed marginal hematological effects within 4 weeks at the HDT. The only
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studies showing a dose related response were the rat subchronic and developmental
toxicity studies in the form of a body weight decrement in female rats and maternal rats,
respectively at the middle and high dose.
An old reproduction study (1973)[See section A.3.3 in Appendix A], that was not
required showed possible, but inconsistent subfertility in rats. This unacceptable
reproduction study may have shown equivocal effects on fertility, litter size at birth and
pup weight decrement at the HDT. The fertility of PO parents was unaffected; the next
generation apparently showed effects at all dose levels, but showed no dose-related
response and in the last generation there was statistically significant dose-related decrease
in fertility at the two top dose levels. The study also showed a peculiar effect at mating.
An unusual number of pregnant females showed no sperm during cohabitation. This
effect is rarely seen in studies on reproduction. However, the method for identification of
sperm at mating was not described and may have been inadequate. Older studies show
more variation in fertility than current studies, raising the question that the potential
decreased fertility may not be reproducible. The study was unacceptable largely due the
variable fertility. For these reasons an extra 3X database uncertainty factor will be used
in the Risk assessment for chlorflurenol methyl ester, unless another study on
reproduction is submitted that shows a more definitive NOAEL for reproductive effects.
3.2 Absorption, Distribution, Metabolism, Excretion (ADME)
Chlorflurenol methyl ester is rapidly absorbed and excreted mostly in the urine
within 24 hours, with minor additional excretion between 24 and 72 hours. In the study
in one female rat/treatment, the report authors claimed that very small amounts of
radiolabel were retained in the mammary gland and barely detectable amounts in nursing
pups. The amount of label retained in the mammary gland and nursing pups was not
quantified, and is thus unknown.
The kinetic data submitted suggest that chlorflurenol in the rat was circulated
enterohepaticaly. Although the data also suggested that chlorflurenol was not secreted in
rat milk, these data were not replicated or quantified and the sensitivity of the radio-
autography/radiological methods used were not described, the absence in the milk supply
was not proven.
3.3 FQPA Considerations
As there are no uses of chlorflurenol methyl ester that qualify as food uses, no
tolerance has been established and the requirements of FQPA are not applicable.
3.4 Hazard Identification and Toxicity Endpoint Selection
3.4.1 Acute Reference Dose (aRfD) - Females age 13-49, Children of the General
Population.
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There is no study with a single dose suitable.
Comment: An acute RfD is used to assess acute food exposure. Since exposure to
chlorflurenol methyl ester does not occur through food, addressing this endpoint is
unnecessary.
3.4.3 Chronic Reference Dose (cRfD)
Selected Study: Chronic Feeding study in Dogs [MRID# 0082863] GDL
870.4100
EXECUTIVE SUMMARY: In a chronic toxicity study (MRID 00082863) IT 3456
[Chlorflurenol, technical (96% a.i., batch/lot # 5/69)] was administered to 4 Beagle
dogs/sex/group in the diet at dose levels of 0, 300, 1000 or 3000 ppm (for male/female
equivalent to 0, 8.7/8.8, 30.6/29.9 or 94.0/94.4 mg/kg bw/day, calculated from test
material consumption) for 104 weeks. One extra dog/sex/group was treated with test
material for 104 weeks, after which the dogs were untreated for 8 weeks. Hematology
and clinical chemistry evaluation was performed at 6 intervals during the study. Animals
were subjected to gross pathology and microscopic examination.
Body weight appeared to be slightly reduced by month 13 at the highest dose
tested [HDT]. Dogs showed this body weight decrement at month 13 when compared
with initial body weights for males [the HDT gained 0% vs. 22.3% for control weight]
and for females [the HDT gained 6.6% vs. 20.3% for control body weight]. Male body
weight gain appeared to be reduced for the remainder of the study. Male body weight
gain was decreased at 104 weeks [body weight gain was 0.8 kg at the HDT and 2.5 kg for
controls]. At the end of the study female body weight gain was the same as control
weight gain. Food consumption was unaffected in both sexes.
Erythrocytes [ERY], hemoglobin concentration [Hb] and hematocrit [Ht] values
appeared to be slightly decreased at the HDT in males and females starting at week 4 [the
first time period evaluated] and male dogs maintained a decrease through out the study.
Some of the values in the HDT were statistically significantly reduced, but were still
within the normal range for dogs. The DERY, DHb and DHt values [difference between
measured values and week -2 values] appeared to decrease in males and females at the
HDT starting at week 4 and male dogs maintained the decrease through out the study.
This decrease is consistent with the slightly higher incidence and/or severity of siderous
in the spleen, liver and Kupffer cells at the HDT. Hemosiderin in the 1000 ppm group
was not considered sufficiently consistent to show that the mid dose group was affected.
In addition the values for ERY, Hb and Ht from the 1000 ppm group of animals did not
show consistent effects. From week 26-52 to termination, the values for ERY, Hb and Ht
for treated female dogs did not appear to differ from control.
Clinical chemistry values showed no consistent treatment related effects. Organ
weights were unchanged from control values.
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On microscopic examination increased hemosiderin in liver and liver Kupffer
cells and possibly in the spleen at the HDT seemed to confirm the hematological effects.
In addition, the highest dose group showed higher incidence of gastritis and possible
stomach lymphatic hyperplasia.
A single dog/sex was allowed to recover for 2 months and although the
hemosiderin appeared to decrease, effects in one dog are difficult to interpret.
The NOAEL was 30.6/29.9 mg/kg/day for males/females. The LOAEL was
94.0/94.4 mg/kg/day for male/females based on decreased erythrocytes, hemoglobin
and hematocrit by week 4 in males and females, supported by hemosiderin deposits
in liver and increased incidence of gastritis and possible decreased body weight in
males and females by month 13 of the study, but not in females by study termination
at 24 months.
This study is ACCEPTABLE/GUIDELINE and satisfies the guideline
requirement [870.4100b] for a dog chronic study. This DER takes precedence over
previous conclusions.
Dose and Endpoint for Establishing cRfD: NOAEL is 31 mg/kg/day. The
LOAEL is 94 mg/kg/day based on male and females decreased erythrocyte, hemoglobin
and hematocrit by week 4 of the study and supported by hemosiderin deposits in the liver
at termination. At this same dose body weight decrement was seen in male and females
at month 13, but not in females by the end of the study.
Uncertainty Factor: 300x [10 for interspecies extrapolation, 10 for intraspecies
variation and 3X for database uncertainty in the NOAEL in a reproduction study].
Comments about the Study/Endpoint/Uncertainty Factor: The hematological
effects occurred at 4 weeks and remained until termination where hemosiderin deposits
confirmed the red blood cell destruction. This endpoint will be unnecessary for current
uses, since there are no food uses. However, this endpoint may be necessary at a later
date and/or handler exposures.
3.4.4 Incidental Oral Exposure (Short- and Intermediate-Term)
Selected Study: Chronic Feeding study in Dogs [MRID 00082863] GDL
870.4100
[See Section 3.5.3 for the executive Summary of MRID 00082863]
Dose for Establishing an Endpoint: NOAEL is 31 mg/kg/day. The LOAEL is 94
mg/kg/day based on male and females decreased erythrocyte, hemoglobin and hematocrit
by week 4 of the study and supported by hemosiderin deposits in the liver at termination.
At this same dose body weight decrement was seen in male and females at month 13, but
not in females by the end of the study.
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Uncertainty Factor: 300x [10 for interspecies extrapolation, 10 for intraspecies
variation and 3X for database uncertainty in the NOAEL in a reproduction study].
Comments about the Study/Endpoint/Uncertainty Factor: The hematological
effects occurred at 4 weeks and remained until termination with hemosiderin
deposits confirming the red blood cell destruction.
3.4.5 Dermal Absorption
There are no dermal absorption studies. Therefore, 100% dermal absorption will
be assumed; exposure will also be calculated assuming 10% dermal absorption for
comparitive purposes
3.4.6 Dermal Exposure (Short-, Intermediate- and Long-Term)
Selected Study: Chronic Feeding study in Dogs [MRID 00082863] GDL
870.4100
[See Section 3.5.3 for the executive Summary of MRID 00082863]
Dose for Establishing an Endpoint: NOAEL is 31 mg/kg/day. The LOAEL is 94
mg/kg/day based on male and females decreased erythrocyte, hemoglobin and hematocrit
by week 4 of the study and supported by hemosiderin deposits in the liver at termination.
At this same dose body weight decrement was seen in males and females at month 13,
but not in females by the end of the study.
Uncertainty Factor: lOOx [10 for interspecies extrapolation, 10 for intraspecies
variation].
Comments about the Study/Endpoint/Uncertainty Factor: The hematological
effects occurred at 4 weeks and remained until termination with hemosiderin
deposits confirming the red blood cell destruction. The 3x uncertainty factor is
dropped for dermal exposure, since an endpoint from an oral study is used. In
addition, since there is no dermal absorption study, the default assumption is
100% dermal absorption, which is excessive. This built in extra safety factor is
adequate, especially since a non-guideline 21-day dermal study on a formulation
showed no systemic toxicity.
3.4.7 Inhalation Exposure (Short-, Intermediate- and Long-Term)
Selected Study: Chronic Feeding study in Dogs [MRID 00082863] GDL
870.4100
[See Section 3.5.3 for the executive Summary of MRID 00082863]
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Dose for Establishing an Endpoint: NOAEL is 31 mg/kg/day. The LOAEL is 94
mg/kg/day based on male and females decreased erythrocyte, hemoglobin and hematocrit
by week 4 of the study and supported by hemosiderin deposits in the liver at termination.
At this same dose body weight decrement was seen in male and females at month 13, but
not in females by the end of the study.
Uncertainty Factor: lOOx [10 for interspecies extraploationvariation, 10 for
intraspecies variation].
Comments about the Study/Endpoint/Uncertainty Factor: The hematological
effects occurred at 4 weeks and remained until termination with hemosiderin
deposits confirming the red blood cell destruction. This endpoint maybe
unnecessary for current uses, since chlorflurenol methyl ester is not irritating and
shows low toxicity by the oral route and effects from inhalation exposure are
unlikely.
3.4.8 Level of Concern for Margin of Exposure
Table 5 Summary of Levels of Concern for Risk Assessment.
Route
Short-Term
(1 - 30 Days)
Intermediate-Term
(1 - 6 Months)
Long-Term
(> 6 Months)
Occupational (Worker) Exposure
Dermal
Inhalation
100
100
100
100
NA
NA
Residential Exposure
Dermal
Inhalation
Incidental Oral
100
NA
300
100
NA
300
NA
NA
300
Occupational exposure: Since oral studies are used for dermal and inhalation
endpoints, there is a built in safety factor associated with absorption which is assumed to
be 100%, but may be much lower.
Residential exposure: Since the potential exists for incidental oral exposure to
infants and children, a 3X database factor is applied when infants or children are exposed.
3.4.9 Recommendation for Combining Exposure Risk Assessments
Since all endpoints are oral, all routes of exposure may be combined, including
incidental oral, dermal and inhalation. However, a combined risk index must be
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used when combining dermal and oral risk because the uncertainty factors
associated with the two types of exposures differ.
3.4.10 Classification of Carcinogenic Potential
There is no indication of dose related or treatment related carcinogenic effects in
males or
females in an acceptable carcinogenicity study in mice below or above the limit dose of
1 g/kg/day [MRID 00082865].
3.4.11 Mutagenicity Studies
A battery of acceptable mutagenicity studies were all negative.
3.4.12 Summary of Toxicological Doses and Endpoints for chlorflurenol methyl
ester for Use in Human Risk Assessments
No studies in humans have been submitted.
Table 6. Summary of Toxicological Doses and Endpoints for Chlorflurenol methyl ester for Use in
Human Health Risk Assessments.
Exposure/
Scenario
Dose Used in Risk
Assessment
Level of Concern
[LOC] for Risk
Assessment and
contributing factors
Study and Toxicological Effects
Acute Dietary
(Females 13-49
years of age)
No studies reflecting a single dose are appropriate or available from which to select this
endpoint.
Acute Dietary
(General
population
including infants
and children)
No studies reflecting a single dose are appropriate or available from which to select this
endpoint.
Chronic Dietary
(All populations)
NOAEL=[31]
mg/kg/day
Chronic RfD = 0.10
mg/kg/day
LOC =100% of the
cRfD. Total UF=300
InterspecieslOX
Intraspecies 10X
Database 3X
Chronic 2-year feeding study in dogs
LOAEL = 94 mg/kg/day based on
decreased erythrocyte, hemoglobin and
hematocrit at 4 weeks.
Incidental Oral
Short-Term
(1 - 30 days) and
Intermediate-Term
(1-6 moths)
NOAEL = 31
mg/kg/day
LOCforMOE = 300
Chronic 2-year feeding study in dogs
LOAEL = 94 mg/kg/day based on
decreased erythrocyte, hemoglobin and
hematocrit at 4 weeks.
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Table 6. Summary of Toxicological Doses and Endpoints for Chlorflurenol methyl ester for Use in
Human Health Risk Assessments.
Exposure/
Scenario
Dermal
Short-Term
(1 - 30 days),
intermediate-Term
(1-6 months) and
Long-Term
(>6moths)
Inhalation
Short-Term
(1 - 30 days),
Intermediate-Term
(1-6 months) and
Log-Term (>6
months)
Cancer (oral,
dermal, inhalation)
Dose Used in Risk
Assessment
NOAEL = 31
mg/kg/day
NOAEL = 31
mg/kg/day
Level of Concern
[LOC] for Risk
Assessment and
contributing factors
LOCforMOE=100
Residential
LOCforMOE=100
Occupational
LOCforMOE= 100
Residential
LOCforMOE= 100
Occupational
Study and Toxicological Effects
Chronic 2-year feeding study in dogs
LOAEL = 94 mg/kg/day based on
decreased erythrocyte, hemoglobin and
hematocrit at 4 weeks.
Chronic 2-year feeding study in dogs
LOAEL = 94 mg/kg/day based on
decreased erythrocyte, hemoglobin and
hematocrit at 4 weeks.
Classification: Chlorflurenol methyl ester is unlikely to be a human carcinogen
UF = uncertainty factor, FQPA SF = Any additional safety factor retained due to concerns unique to the
FQPA, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, PAD =
population adjusted dose (a = acute, c = chronic) RfD = reference dose, MOE = margin of exposure, LOC =
level of concern, NA = not applicable
4.0 Public Health and Pesticide Epidemiology Data
Incidence reports /epidemiology data are not available at this time. However,
given the minimal nature of acute toxicity (Toxicity Categories III for eye and IV for
other acute studies, large numbers of incidence are not expected.
5.0 Dietary Exposure/Risk Characterization
Chlorflurenol methyl ester is a nonfood use pesticide having no tolerances to
reassess. Consequently, there are no residue chemistry data requirements and thus,
dietary exposure or risk assessments are not applicable. Chlorflurenol methyl ester is
used on pineapple after fruit harvest to stimulate production of vegetative planting
material (slips). The time between pesticide treatment and the first harvest of pineapple
fruit would be 1.5 to 2 years. No residues are expected in the fruit according to a HED
Greyberad Committee decision in 1995 [TXR# 012504]. HED upholds this decision in
this RED chapter.
5.1 Drinking Water Residue Profile
It should be noted that drinking water exposure to Chlorflurenol methyl ester is
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very limited. Due to the limited number of pound per year used, this water contamination
is likely limited to use areas only. It follows that expanded use, would result in additional
contamination.
Chronic drinking water exposure were modeled by DEEM software using surface
water concentration, which showed all groups were exposed to levels below the chronic
oral endpoint of 0.1 mg/kg/day. Non-nursing infants and all infants (< one year) were
exposed to highest percentage of the RfD at 20% and 16 % respectively. All other
groups were exposed to drinking water at 7.4% to 4.7% of the oral chronic RfD of 0.1
mg/kg/day. These levels are below EPA LOG. Selected levels for the highest exposure
within a group are given in Table 7a
However, it should be noted that toddlers exposed to spray and granular treated
lawns are above HED's LOG. Any additional exposure from water would exacerbate this
concern.
Table 7a Selected population exposures (selected for highest surface water exposures within a group)
Population subgroup
US population (summer season)
Western region
Hispanics
Non-hispanic blacks
Non-hispanic/non-white/non-black
All infants (Kyear)]
Nursing infants
Non-nursing infants
Females 20+ (not pregnant or
nursing)
Females 13-50 years
Females 13+ nursing
Males 20+ yrs
Seniors 55+
Children 1-2 years
Children 3 -5 years
Children 6-12 years
Youths 13-19 yrs
Mg/kg/day a
0.005343
0.005699
0.005646
0.004722
0.006098
0.016308
0.006049
0.020201
0.004965
0.004812
0.006891
0.004457
0.004883
0.007387
0.006915
0.004770
0.003596
Margin of
exposure
5,802
5,439
5,490
6,565
5084
1,901
5,125
1,535
6.243
6,442
4,498
6,955
6,348
4.197
4,483
6,499
8,622
% of the endpoint of 0. 10
mg/kg/day
5.3%
5.7%
5.6%
4.7%
6.1%
16.3%
6.0%
20.2%
5.0%
4.8%
6.9%
4.5%
4.9%
7.4%
6.9%
4.8%
3.6%
a For drinking water, Deem software was modeled using surface water concentration at 236 ppb.
Chronic drinking water exposures were also modeled by DEEM software using
estimated ground water concentration, where only two groups were exposed to levels
above the LOG. Non-nursing infants and all infants (< one year) were exposed to highest
percentage of the RfD at 176% and 142% respectively. All other groups were exposed to
drinking water at 31% to 60% of the oral chronic RfD of 0.1 mg/kg/day. The 176% and
142% are above OPP'sLOC. Selected levels for the highest exposure within a group
are given in Table 7b
Table 7b Selected population exposures (selected for highest ground water exposures within a group)
Population subgroup | Mg/kg/day a |% of the endpoint of 0.10 mg/kg/day
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US population (summer season)
Western region
Hispanics
Non-hispanic blacks
Non-hispanic/non-white/non-black
All infants (Kyear)]
Nursing infants
Non-nursing infants
Females 20+ (not pregnant or
nursing)
Females 13-50 years
Females 13+ nursing
Males 20+ yrs
Seniors 55+
Children 1-2 years
Children 3 -5 years
Children 6-12 years
Youths 13-19 yrs
0.046414
0.049506
0.049046
0.041015
0.052870
0.141662
0.052540
0.175478
0.043131
0.041801
0.059862
0.038717
0.042420
0.064165
0.060069
0.041432
0.031233
46.2%
49.5%
49.0%
41.0%
53.0%
141.7%
52.5%
175.5%
43.1%
41.8%
59.9%
38.7%
42.4%
64.2%
60.1%
41.4%
31.2%
For drinking water, Deem software was modeled using ground water concentration at 2050 ppb.
Potential drinking water residues were estimated for groundwater from Tier I
SCIGROW and surface water from Tier II PRZM and EXAMS models. The
environmental fate information is incomplete. Due to this incomplete information,
conservative default values have been substituted for missing data in order to proceed
with this assessment. The OPP/EFED Florida turf scenario was selected for this
assessment as a worst case based on the available usage and environmental fate
information. It is likely that a more complete database for this chemical would lead to
reduced estimates of chlorflurenol methyl ester concentrations in drinking water. For this
assessment, it was assumed that 8 applications of chlorflurenol methyl ester were applied
to turf grass at a rate of 3.0 pounds active ingredient per acre with a 28 day interval
between applications and the pesticide is stable in the environment. The acute and
chronic groundwater concentration of 2050 ppb is the highest estimated values. This
would represent a maximum concentration in a shallow, private well in a high usage area.
Surface water concentrations are for acute concentration: 386 ppb; for chronic non-
cancer: 236 ppb and for ground water concentration 2050 pbb. [Table 8].
Table 8 Summary of Estimated Surface Water and Groundwater Concentrations for [Chemical].
Acute
Chronic (non-cancer)
[Chemical]
Surface Water Cone., ppb a
386
236
Groundwater Cone., ppb b
2050
2050
a From the Tier II PRZM-EXAMS - Index Reservoir model. Input parameters are based on OPP/EFED Florida
Turf scenario.
b From the SCI-GROW model assuming a maximum seasonal use rate of 3 Ib a.i./A, 8 applications/year spaced at
28 day intervals; a Koc of 65 L/mg and stable 1A life.
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5.2 Food Residue Profile
There are no residues in food.
6.0 Residential Exposure and Risks
Chlorflurenol methyl ester is an herbicide, plant growth retardant, and plant
growth regulator that is used in agricultural, commercial, and residential settings. As an
herbicide and/or plant growth retardant, chlorflurenol is used for the postemergent control
of annual grasses, broadleaf weeds, trees, shrubs, and vines. As a plant growth regulator,
chlorflurenol is used in the production of pineapple planting material (sliplets).
Chlorflurenol is registered as emulsifiable concentrate and granular formulations. The
emulsifiable concentrate formulations are applied using groundboom sprayer, rights-of-
way sprayer, handgun sprayer, low pressure handwand sprayer, and airblast sprayer.
Granular formulations are applied using a bellygrinder, push-type spreader, and tractor-
drawn spreader.
Hazard Concerns
Adverse effects were identified at durations of exposure ranging from short-term
(up to 30 days) to long-term (> 6 months). The short- and intermediate-term dermal,
inhalation, and incidental oral endpoints are based on a NOAEL of 31 mg/kg/day from a
chronic 2-year feeding study in dogs where the LOAEL is 94 mg/kg/day. The LOAEL is
based on decreased erythrocyte, hemoglobin and hematocrit at 4 weeks. Long-term
exposures to chlorflurenol (i.e., greater than 6 months) are not expected for current
registered uses. Additionally, no cancer endpoint was identified; therefore cancer risks
are not assessed.
HED's level of concern (LOG) for chlorflurenol methyl ester occupational and
residential dermal and inhalation exposures is 100 (i.e., a margin of exposure (MOE) less
than 100 exceeds HED's level of concern). The dermal and inhalation margins of
exposure were combined for the occupational and residential handler risk assessments
because the toxicity endpoints for the dermal and inhalation routes of exposure are based
on the same toxicological effects. For incidental oral exposures, HED's level of concern
is 300 (i.e., a margin of exposure (MOE) less than 300 exceeds HED's level of concern).
The dermal and incidental oral ingestion margins of exposure for the residential
postapplication risk assessments for toddlers were also combined because the toxicity
endpoints for the dermal and oral routes of exposure are based on the same toxicological
effects.
6.1 Residential Handler Exposures and Non-cancer Risk Estimates
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It has been determined there is a potential for exposure in residential settings
during the application process for homeowners who use granular products containing
chlorflurenol. There is also a potential for exposure from entering chlorflurenol-treated
areas, such as lawns and golf courses. Risk assessments have been completed for both
residential handler and postapplication scenarios.
In addition to homeowner uses in residential settings, chlorflurenol products are
labeled for weed control at residential settings, which is applied by occupational
applicators, but may result in postapplication exposures in residential settings. These
potential postapplication exposures to homeowners also have been considered in this
assessment.
6.1.1 Residential Handler Exposures and Risks
HED uses the term "handlers" to describe those individuals who are involved in
the pesticide application process. HED believes that there are distinct tasks related to
applications and that exposures can vary depending on the specifics of each task as was
described under occupational handlers.
6.1.2 Handler Exposure Scenarios
Scenarios are used to define risks based on the U.S. EPA Guidelines for Exposure
Assessment (U.S. EPA; Federal Register Volume 57, Number 104; May 29, 1992).
Assessing exposures and risks resulting from residential uses is very similar to assessing
occupational exposures and risks, with the following exceptions:
• Residential handler exposure scenarios are considered to be short-term only, due to
the infrequent use patterns associated with homeowner products.
• A tiered approach for personal protection using increasing levels of PPE is not used in
residential handler risk assessments. Homeowner handler assessments are based on
the assumption that individuals are wearing shorts, short-sleeved shirts, socks, and
shoes.
• Homeowner handlers are expected to complete all tasks associated with the use of a
pesticide product including mixing/loading if needed as well as the application.
• Label use-rates and use-information specific to residential products serve as the basis
for the risk calculations.
• Area/volumes of spray or chemical used in the risk assessment are based on HED's
guidance specific to residential use-patterns.
75
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HED has determined that there is potential exposure to residential mixer, loader,
and applicators during the usual use-patterns associated with chlorflurenol. Based on the
use patterns, two major residential exposures were identified.
Mixers/Loaders/Applicators
(1) Mixing/loading/applying granular with push-type spreader (ORETF); and
(2) Mixing/loading/applying gra nular with a belly grinder (PHED).
6.1.3 Data and Assumptions for Handler Exposure Scenarios
A series of assumptions and exposure factors served as the basis for completing
the residential handler risk assessments. Each assumption and factor is detailed below. In
addition to these factors, unit exposure values were used to calculate risk estimates.
These unit exposure values were taken from the Outdoor Residential Exposure Task
Force (ORETF) studies. Both PHED and ORETF studies are presented below.
Assumptions and Factors: The assumptions and factors used in the risk
calculations include:
• Exposure factors used to calculate daily exposures to handlers were based on
applicable data, if available. When appropriate data is unavailable, values from a
scenario deemed similar might be used.
• FLED always considers the maximum application rates allowed by labels in its risk
assessments. If additional information such as average or typical rates is available,
these values also may be used to allow risk managers to make a more informed risk
management decision. Average/typical application rates were not available for
residential scenarios.
• Residential risk assessments are based on estimates of what homeowners would
typically treat, such as the size of a lawn or the size of a garden. The factors used for
the chlorflurenol assessment were from the Health Effects Division Science Advisory
Committee Policy 12: Recommended Revisions to the Standard Operating
Procedures for Residential Exposure Assessment which was completed on February
22, 2001, and on professional judgment. The daily volumes handled and area treated
used in each residential scenario are provided in Table 2 of that policy
recommendation.
Residential Handler Exposure Studies: The unit exposure values that were used in this
assessment were based on the Outdoor Residential Exposure Task Force studies and the
Pesticide Handler Exposure Database (PHED, Version 1.1 August 1998). The ORETF
data used in the residential assessment is described below.
76
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ORETF Handler Studies - OMA001-OMA004 (MRID 449722-01)
A report was submitted by the ORETF (Outdoor Residential Exposure Task Force) that
presented data in which the application of various products used on turf by homeowners
and lawncare operators (LCOs) was monitored. All of the data submitted in this report
were completed in a series of studies.
OMA003: Homeowner Granular Applications with a Rotary (Push-type) Spreader
(MRID 449722-01): A mixer/loader/applicator study was performed by the Outdoor
Residential Exposure Task Force (ORETF) using Dacthal (active ingredient DCPA,
dimethyl tetrachloroterephthalate) as a surrogate compound to determine "generic"
exposures of individuals applying a granular pesticide formulation to residential lawns.
A total of 30 volunteers were monitored using passive dosimetry (inner and outer whole
body dosimeters, hand washes, face/neck wipes, and personal inhalation monitors). Each
volunteer carried, loaded, and applied two 25-lb bags of fertilizer (0.89% active
ingredient) with a rotary type spreader to a lawn covering 10,000 ft2. The target
application rate was 2 Ib a.i./acre (actual rate achieved was about 1.9 Ibs a.i./acre). The
average application time was 22 minutes, including loading the rotary push spreader and
disposing of the empty bags. Each replicate handled approximately 0.45 Ibs a.i. Dermal
exposure was measured using inner and outer whole body dosimeters, hand washes,
face/neck washes, and personal air monitoring devices with OVS tubes. The results for
the rotary (push-type) spreader are summarized in Table 9 below.
Table 9: Unit Exposure Values for Homeowner Granular Applications with a
Rotary (Push-type) Spreader Obtained From ORETF Study (MRID 449722-01)
Scenario Monitored
Homeowner Granular Applications
with a Push-type Spreader
Unit Exposures
Dermal
(mg a.i./lb handled)
Short Pants, Short
Sleeves
0.67
Long Pants, Short
Sleeves
0.09
Long Pants, Long
Sleeves
0.07
Inhalation
(Hg a.i./lb handled)
0.88
1 All unit exposure values are geometric means.
6.1.4 Residential Handler Exposure and Non-Cancer Risk Estimates
Non-cancer risks were calculated using the Margin of Exposure (MOE) as
described in Section 7.1.3. Assessing exposures and risks resulting from residential uses
is very similar to assessing occupational exposures and risks, except as described in
Section 7.1.1. The other major difference with residential risk assessments is that the
uncertainty factor which defines the level of risk concern has the additional FQPA safety
factor applied. In the case of chlorflurenol, it was decided by FED that the factor for
handler risk assessments is 100, which is based on the FQPA safety factor of IX along
with the 10X for inter-species extrapolation and 10X for intra-species sensitivity.
77
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The residential exposure and risk estimates associated with the use of
chlorflurenol are presented in Table 10. The risk calculations for residential chlorflurenol
handlers are included in Appendix D of the June 30, 2006 Chlorflurenol Methyl Ester:
Occupational and Residential Exposure Assessment for the RED.
Table 10: Residential Handler Short- and Intermediate-term Dermal, Inhalation and Total Exposure
and Risks
Exposure
Scenariol
Crop
or
Target
Applicatio
nRate
Area
Treated
Daily
(acres)
Baseline Unit
Exposures
Dermal
(mg/lb
a.i.)
Inhalatio
n (|ig/lb
a.i.)
Baseline MOEs
(Level of Concern = 100)
Dermal
Inhalation
Total
Mixer/Loader/Applicator
1)
Mixing/loading/
applying
granular with
push-type
spreader
(ORETF OMA
003)
2)
Mixing/loading/
applying with a
belly grinder
(PHED)
Turf
Turf
0.25 Ib.
a. i. /acre
(Label -
100%
DA)
0.25 Ib.
a. i. /acre
(Label -
10% DA)
0.25 Ib.
a. i. /acre
(Label -
100%
DA)
0.25 Ib
ai/acre
(Label -
10% DA)
0.5 acres
0.023
0.67
110
0.88
62
26,000
260,000
3,400
34,000
2,000,000
20,000,00
0
6,100,000
61,000,00
0
26,000
260,00
0
3,400
34,000
6.1.5 Residential Handler Exposure and Risk Estimates for Cancer
No cancer endpoints of concern for chlorflurenol were identified; therefore cancer
risks to residential handlers were not assessed.
6.1.6 Summary of Risk Concerns and Data Gaps for Handlers
All non-cancer risks (i.e., MOEs) to handlers associated with the scenarios are not
of concern, because they exceed HED's uncertainty factor of 100.
6.1.7 Recommendations for Refining Residential Handler Risk
Assessment
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In order to refine this residential risk assessment, more data on actual use patterns
including rates, timing, and areas treated would better characterize chlorflurenol risks.
Exposure studies for many equipment types that lack data or that are not well represented
in PHED (e.g., because of low replicate numbers or data quality) should also be
considered based on the data gaps identified above and based on a review of the quality
of the data used in this assessment.
6.2 Residential Postapplication Exposures and Assumptions
HED uses the term "postapplication" to describe exposures to individuals that
occur as a result of being in an environment that has been previously treated with a
pesticide. Chlorflurenol can be used in many areas that can be frequented by the general
population including residential areas (e.g., home lawns and gardens). As a result,
individuals can be exposed by entering these areas if they have been previously treated.
6.2.1 Residential Postapplication Exposure Scenarios
A wide array of individuals of varying ages can potentially be exposed to
chlorflurenol when they are in areas that have been previously treated. Postapplication
exposure scenarios were developed for each residential setting where chlorflurenol can be
used. The scenarios likely to result in postapplication exposures are as follows:
• Dermal exposure from residue on lawns and turf (adult, youth and toddler);
• Hand-to-mouth transfer of residues on lawns (toddler);
• Ingestion of pesticide treated grass (toddler); and
• Incidental ingestion of soil from pesticide-treated residential areas (toddler).
Incidental ingestion of chlorflurenol granules from pesticide-treated residential areas
was not assessed because there an acute dietary endpoint was not identified.
HED relies on a standardized approach for completing residential risk assessments
that is based on current labels and guidance contained in the following four documents:
• Series 875, Residential and Residential Exposure Test Guidelines: Group B -
Postapplication Exposure Monitoring Test Guidelines (V5.4, Feb. 1998) This
document provides general risk assessment guidance and criteria for analysis of
residue dissipation data.
• Standard Operating Procedures for Residential Exposure Assessment (Dec. 1997)
This document provides the overarching guidance for developing residential risk
assessments including scenario development, algorithms, and values for inputs.
• Science Advisory Council For Exposure Policy 12 (Feb. 2001): Recommended
Revisions To The Standard Operating Procedures (SOPs) For Residential
Exposure Assessment This document provides additional, revised guidance for
79
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completing residential exposure assessments.
• Overview of Issues Related To The Standard Operating Procedures For Residential
Exposure Assessment (August 1999 Presentation To The FIFRA SAP) This
document provides rationale for Agency changes in SOPs.
When the guidance in current labels and these documents is considered, it is clear
that HED should consider children of differing ages as well as adults in its assessments.
It is also clear that different age groups should be considered in different situations. The
populations that were considered in the assessment include:
• Residential Adults: these individuals are members of the general population that are
exposed to chemicals by engaging in activities at their residences (e.g., in their lawns
or gardens) and also in areas not limited to their residence (e.g., golf courses or parks)
previously treated with a pesticide. These kinds of exposures are attributable to a
variety of activities and are usually addressed by HED in risk assessments by
considering a representative activity as the basis for the exposure calculation.
• Residential Children: children are members of the general population that can also be
exposed in their residences (e.g., on lawns and other residential turf grass areas).
These kinds of exposures are attributable to a variety of activities such as playing
outside. Toddlers have been selected as the sentinel (representative) population for
the turf assessment. Youth-aged children (ages 10 to 12) are considered the sentinel
population for a golfing assessment, because it is likely that children of this age
would be playing golf. Children are addressed by HED in risk assessments by
considering representative activities for each age group in an exposure calculation.
The SOPs for Residential Exposure Assessment defines several scenarios that
apply to uses specified in current labels. These scenarios served as the basis for the
residential postapplication assessment along with the modifications to them and the
additional data and approaches described above. HED used this guidance to define the
exposure scenarios that essentially include dermal and nondietary ingestion exposure to
toddlers on treated lawns and dermal exposure to adults and youth on treated lawns. The
SOPs and the associated scenarios are presented below:
• Dose from dermal exposure on treated turf: Postapplication dermal dose
calculations for toddlers from playing on treated turf, for youth and adults playing
golf on treated turf, and for adults mowing and exercising on treated turf
• Dose from hand-to-mouth activity from treated turf: Postapplication dose
calculations for toddlers from incidental nondietary ingestion of pesticide residues on
treated turf from hand-to-mouth transfer (i.e., those residues that are swallowed when
toddlers get pesticide residues on their hands from touching treated turf and then put
their hands in their mouth);
80
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• Dose from object-to-mouth activity from treated turf: Postapplication dose
calculations for toddlers from incidental nondietary ingestion of pesticide residues on
treated turf from object-to-mouth transfer (i.e., those residues that are swallowed
when toddlers put treated turf in their mouths);
• Dose from soil ingestion activity from treated turf: Postapplication dose calculations
for toddlers from incidental nondietary ingestion of pesticide residues from ingesting
soil in a treated turf area (i.e., those soil residues that are swallowed when toddlers get
pesticide residues on their hands from touching treated soil and then put their hands in
their mouth); and
The detailed residential postapplication calculations are presented in Appendix E of this
document.
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6.2.2 Data and Assumptions for Residential Postapplication
Exposure Scenarios
Assumptions and Exposure Factors
A series of assumptions and exposure factors served as the basis for completing
the residential postapplication risk assessments. The assumptions and factors used in the
risk calculations are consistent with current Agency policy for completing residential
exposure assessments (i.e., SOPsfor Residential Exposure Assessment). The values used
in this assessment include:
• There are many factors that are common to the occupational and residential
postapplication risk assessments, such as body weights for adults, and analysis of
residue dissipation data. Please refer to the assumptions and factors in Section 7.1.2
for further information concerning these common values.
• HED combines risks resulting from exposures to individual applications when it is
likely they can occur simultaneously based on the use pattern and the behavior
associated with the exposed population. The toxicological endpoints used in
assessing risks must have the same toxicological effect in order for the risks to be
combined. HED has combined risks using the aggregated risk index (ARI) for
different kinds of exposures for the following scenario: toddlers on turf- dermal
(high contact lawn activity) plus hand-to-mouth plus object-to-mouth plus soil
ingestion.
• Exposures to adults and children on treated turf have been addressed using the latest
HED standard operating procedures for this scenario including:
o the transfer coefficients used are those presented during the 1999 Agency
presentation before the FIFRA Science Advisory Panel that have been
adopted in routine practice by HED;
o 3 year old toddlers are expected to weigh 15 kilograms (representing an
average weight from years one to six);
o hand-to-mouth exposures are based on a frequency of 20 events/hour and
a surface area per event of 20 cm2, representing the palmar surfaces of
three fingers;
o saliva extraction efficiency is 50 percent meaning that every time the hand
goes in the mouth approximately /^ of the residues on the hand are
removed;
o object-to-mouth exposures are based on a 25 cm2 surface area;
o ingestion rate of soil is 100 mg/day;
o exposure durations for turfgrass scenarios are estimated to be 2 hours and
exposure durations for home gardening (ornamental) scenarios are
estimated to be 0.67 hours for adults and 0.33 hours for youth - based on
82
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information in HED's Exposure Factors Handbook,
o soil residues are contained in the top centimeter and soil density is 0.67
mL/gram; and
o dermal, hand- and object-to-mouth, and soil ingestion are combined to
represent an overall risk from exposure to turf.
• Postapplication residential risks are based on maximum application rates or values
specified in the SOPs for Residential Exposure Assessment.
• The Jazzercize approach is the basis for the dermal transfer coefficients as described
in HED's Series 875 guidelines, SOPs for Residential Exposure Assessment, and the
1999 FIFRA SAP Overview document.
6.2.3 Residential Postapplication Exposure and Non-cancer Risk
Estimates
Non-cancer risks were calculated using the Margin of Exposure (MOE) approach,
which is a ratio of the body burden to the toxicological endpoint of concern. Exposures
were calculated by considering the potential sources of exposure (i.e., TTRs on lawns),
then calculating dermal and nondietary ingestion exposures.
Dermal exposures and risks from lawn uses were calculated in the same manner
as described above in Section 7.2.3. Along with calculating these dermal exposures,
other aspects of the turf exposure scenarios were calculated such as the dose from
nondietary ingestion. The algorithms used for each type of calculation are presented
below which have not been previously addressed in Section 7.2.3.
Nondietary Ingestion Exposure from Treated Turf: Nondietary ingestion
exposure from treated turf was calculated using the following equations. These values
were then used to calculate MOEs.
Dermal Exposure from Treated Lawns (adult and toddler)
The approach used to calculate the dermal doses that are attributable to exposure
from contacting treated lawns is:
ADD = (TTR0 *ET*TC*DA* CF1) /BW
Where:
ADD = average daily dose (mg/kg/day);
TTRt = turf transferable residue on day "0" (jig/cm2). TTR = application
rate (|ig/cm2) * fraction of a.i. retained on foliage (5% for turf
activities, 20% for gardening activities);
ET = exposure time (2 hr/day);
83
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TC = transfer coefficient (14,500 cm2/hr for adults and 5,200 cm2/hr for
toddlers);
DA = dermal absorption factor;
CF1 = weight unit conversion factor to convert jig units to mg for the
daily exposure (0.001 mg/|ig); and
BW = body weight (70 kg for adults and 15 kg for toddlers).
Hand-to-mouth Transfer of Pesticide Residues on Lawns (toddler)
The approach used to calculate the nondietary ingestion exposures that are
attributable to hand-to-mouth behavior on treated turf is:
ADD = (TTR0 *SA*FQ*ET*SE* CF1) /BW
Where:
ADD = average daily dose (mg/kg/day);
TTRt = turf transferable residue on day "0" (jig/cm2); TTR = application
rate (jig/cm2) * fraction of a.i. retained on foliage (5%);
SA = surface area of the hands (20 cm2/event);
FQ = frequency of hand-to-mouth activity (20 events/hr);
ET = exposure time (2 hr/day);
SE = extraction by saliva (50%);
CF 1 = weight unit conversion factor to convert jig units in the TTR value
to mg for the daily exposure (0.001 mg/|ig); and
BW = body weight (15 kg).
Object-to-mouth Transfer of Pesticide Residues on Lawns (toddler)
The approach used to calculate doses that are attributable to object-to-mouth
behavior on treated turf that is represented by a child mouthing on a handful of turf is:
ADD = (TTR0 * IgR* CF1) /BW
Where:
ADD = average daily dose (mg/kg/day);
TTRt = turf transferable residue on day "0" (jig/cm2); TTR = application
rate (jig/cm2) * fraction of a.i. retained on foliage (20%)
IgR = ingestion rate of grass (25 cm2/day);
CF 1 = weight unit conversion factor to convert the jig of residues on the
grass to mg to provide units of mg/day (1E-3 mg/|ig); and
BW = body weight (15 kg).
Incidental Ingestion of Soil from Pesticide-Treated Residential Areas (toddler)
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The approach used to calculate doses that are attributable to soil ingestion is:
ADD = (SR0 * IgR * CF1) /BW
Where:
ADD = average daily dose (mg/kg/day);
SRot = soil residue on day "0" (0.0022 |ig/g);
IgR = ingestion rate of soil (lOOmg/day);
CF1 = weight unit conversion factor to convert the jig of residues on the
soil to grams to provide units of mg/day (1E-6 g/|ig); and
BW = body weight (15 kg).
And
SRt=AR*F* CF2 * CF3 * CF4
Where:
AR = application rate (Ib a.i./acre);
F = fraction of a.i. available in uppermost cm of soil (1 fraction/cm)
(100%);
CF2 = volume to weight unit conversion factor to convert the volume
units (cm3) to weight units for the SR value (U.S. EPA, 1992)
(0.67 cm3/g soil);
CF3 = area unit conversion factor to convert the surface are units (acres)
in the application rate to cm2 (2.47E-8 acre/cm2); and
CF4 = weight unit conversion factor to convert the Ibs a.i. in the
application rate to jig (4.54E8 |ig/lb).
Non-cancer Risk Summary
Adults
Table 11 presents the postapplication MOE values calculated for adults after lawn,
turf and home garden applications chlorflurenol. All postapplication non-cancer risks
were below FtED's level of concern, except for high contact activities on residential turf
assuming the 3.0 Ib a.i./A (BEAD) application rates where MOEs are 44 on day 0.
Table 11: Adult Residential Risk Estimates (Dermal) for Postapplication Exposure
Exposure Scenario
Dermal
Transfer
Coefficient
(|ig/cm2)
Application
Rate
(Ib a.i./acre)
MOE at Day 0
(Level of
Concern = 100)
Spray
85
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Table 11: Adult Residential Risk Estimates (Dermal) for Postapplication Exposure
Exposure Scenario
Residential Turf (High Contact
Activities)
Residential Turf (Mowing)
Golfer
Dermal
Transfer
Coefficient
(|ig/cm2)
14,500
3,400
500
Application
Rate
(Ib a. i. /acre)
1.0 (Label)
3.0 (BE AD)
1.0 (Label)
3.0 (BE AD)
1.0 (Label)
3.0 (BE AD)
MOE at Day 0
(Level of
Concern = 100)
130
44
570
190
1,900
650
Granular
Residential Turf (High Contact
Activities)
Residential Turf (Mowing)
Golfer
14,500
3,400
500
1.1 (Label -
100% DA)
1.1 (Label -
10% DA)
3.0 (BEAD -
100% DA)
3.0 (BEAD -
10% DA)
1.1 (Label -
100% DA)
1.1 (Label -
10% DA)
3.0 (BEAD -
100% DA)
3.0 (BEAD -
10% DA)
1.1 (Label -
100% DA)
1.1 (Label -
10% DA)
3.0 (BEAD -
100% DA)
3.0 (BEAD -
10% DA)
120
1,200
44
440
520
5,200
190
1,900
1,800
18,000
650
6,500
Youths (11-12 years old)
Table 12 summarizes the risk assessment for youths [10 to 12 years old]. Short-
term MOEs for chlorflurenol for these youths were >100 for all scenarios considered.
86
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Table 12: Youth Residential Risk Estimates (Dermal) for Postapplication
Exposure
Exposure Scenario
Dermal
Transfer
Coefficient
(|ig/cm2)
Application
Rate
(Ib a. i. /acre)
MOE at Day 0
(Level of
Concern = 100)
Spray
Residential Turf (Mowing)
Golfer
3,400
500
1.0 (Label)
3.0 (BEAD)
1.0 (Label)
3.0 (BEAD)
320
110
1,100
360
Granular
Residential Turf (Mowing)
Golfer
3,400
500
1.1 (Label-
100% DA)
1.1 (Label- 10%
DA)
3.0 (BEAD -
100% DA)
3.0 (BEAD -
10% DA)
1.1 (Label-
100% DA)
1.1 (Label- 10%
DA)
3.0 (BEAD -
100% DA)
3.0 (BEAD -
10% DA)
290
2,900
110
1,100
980
9,800
360
3,600
Toddler (3 year old)
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Table 13 summarizes the risk assessment for toddlers. The
postapplication non-cancer risks are not of concern for the oral route (MOE's >300). For
the dermal route, risks to toddlers from high contact activity on lawns exceed HED's
level of concern (MOE's <100) at the 1.0/1.1 Ib a.i./A (Label) and 3.0 Ib a.i./A (BEAD)
application rates, except when 10% dermal absorption is assumed for the granular
formulations. Calculated combined risks to toddlers (i.e., dermal high contact activity
plus hand to mouth activity plus object to mouth activity on treated turf plus incidental
soil ingestion of pesticide residue from treated turf areas) are therefore, also of concern,
except when 10 percent dermal absorption is assumed for the granular formulations.
Table 13: Toddler Residential Risk Estimates for Postapplication Exposure
Exposure Scenario
Route of
Exposure
Dermal
Transfer
Coefficient
(|ig/cm2)
Application
Rate
(Ib a. i. /acre)
MOE at Day 0
(Level of
Concern = 100
for dermal and
300 for oral)
Spray
Residential Turf (High Contact
Activities)
Hand to Mouth Activity on Turf
Object to Mouth Activity on Turf
Incidental Soil Ingestion
Dermal
Oral
5,200
NA
NA
NA
1.0 (Label)
3.0 (BEAD)
1.0 (Label)
3.0 (BEAD)
1.0
3.0 (BEAD)
1.0
3.0 (BEAD)
80
27
2,100
690
8,300
2,800
620,000
210,000
Granular
Residential Turf (High Contact
Activities)
Hand to Mouth Activity on Turf
Object to Mouth Activity on Turf
Incidental Soil Ingestion
Dermal
Oral
5,200
NA
NA
NA
1.1 (Label
100% DA)
1.1 (Label 10%
DA)
3.0 (BEAD -
100% DA)
3.0 (BEAD -
10% DA)
1.1
3.0 (BEAD)
1.1
3.0 (BEAD)
1.1
3.0(BEAD)
72
720
27
270
1,900
690
7,500
2,800
560,000
210,000
88
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Combined Risk Assessment for Residential Scenarios
HED combines risk values resulting from separate postapplication exposure
scenarios when it is likely they can occur simultaneously based on the use-pattern and the
behavior associated with the exposed population. In the case of the chlorflurenol, the
dermal and incidental oral ingestion toxicological endpoints have the same toxicological
effect, therefore dermal and oral doses were combined.
A total aggregated risk index (ARI) was used since the target MOE values for
dermal exposure (100) and incidental oral exposure (300) are different. The target ARI is
1; therefore, ARIs of less than 1 are risks of concern. The combined risk index was
calculated from the aggregate risk index (ARI)-as follows.
Aggregate Risk Index (ARI) = l/(l/RIhigh contact activity) + (1/RIhand-to-mouth) + (l/RI0bject-to-
mouthy ~"~ vl'^-Mncidental soil ingestion/
Where:
Risk Index (RI) = MOE/Uncertainty Factor
Table 14 summarizes the combined risk assessment for toddlers. Calculated
combined risks to toddlers (i.e., dermal high contact activity, hand-to-mouth activity,
object-to-mouth activity on treated turf plus incidental soil ingestion of pesticide residue
from treated turf areas) are of concern for applications of chlorflurenol at:
• 1.0 Ib a.i./A (label) for spray applications assuming 100% dermal absorption (ARI
= 0.70);
• 1.1 Ib a.i./A (label and 100% dermal absorption) for granular applications (ARI =
0.63)
• 3.0 Ib a.i./A (BEAD) for spray applications assuming 100% dermal absorption (ARI
= 0.23); and
• 3.0 Ib a.i./A (BEAD) for granular applications assuming 100% dermal absorption
(ARI = 0.23.
The ARIs are greater than 1 for the 1.1 and 3.0 Ib a.i./A (label and BEAD
respectively) for granular applications if 10% dermal absorption is assumed. The ARI for
the 1.1 Ib a.i./A scenario is 3 and the ARI for the 3 Ib a.i./A scenario is 1.1.
Table 14: Residential Scenarios for Short-Term Risk Estimates - Toddlers
Postapplication Exposure Scenario
Toddler
Turf- Spray
Application
Dermal - High
Contact Activity
Risk Index (RI)
0.80
Combined-Risk
Index (ARI)
0.70
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Table 14: Residential Scenarios for Short-Term Risk Estimates - Toddlers
Postapplication Exposure Scenario
(1.0 Ib a.i./acre -
Label)
Turf- Spray
Application
(3.01b a.i./acre-
BEAD)
Turf- Granular
Application
(1 . 1 Ib a.i./acre - Label
- 100% DA)
Turf -Granular
Application
(1.1 Ib a.i./acre - Label
- 10% DA)
Turf -Granular
Application
(3.0 Ib a.i./ acre -
BEAD- 100% DA)
Turf- Granular
Application
(3.01b a.i./acre-
BEAD- 10% DA)
Hand to Mouth
Object to Mouth
Incidental Soil
Ingestion
Dermal - High
Contact Activity
Hand to Mouth
Object to Mouth
Incidental Soil
Ingestion
Dermal - High
Contact Activity
Hand to Mouth
Object to Mouth
Incidental Soil
Ingestion
Dermal - High
Contact Activity
Hand to Mouth
Object to Mouth
Incidental Soil
Ingestion
Dermal - High
Contact Activity
Hand to Mouth
Object to Mouth
Incidental Soil
Ingestion
Dermal - High
Contact Activity
Hand to Mouth
Object to Mouth
Incidental Soil
Ingestion
Risk Index (RI)
6.9
27
2100
0.27
2.3
9.2
688
0.72
6.3
25
1800
7.3
6.3
25
1800
0.27
2.3
9.2
688
2.7
2.3
9.2
688
Combined-Risk
Index (ARI)
0.23
0.63
3
0.23
1.1
6.2.4 Residential Postapplication Exposure and Risk Estimates for
Cancer
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Residential postapplication cancer risks were not assessed for chlorflurenol
because no cancer endpoints of concern were identified.
6.2.5 Summary of Residential Postapplication Risk Concerns and
Data Gaps
HED considered a number of exposure scenarios for products that can be used in
the residential environment representing different segments of the population including
toddlers, youth-aged children, and adults. Short-term non-cancer MOEs were calculated
for all scenarios. Cancer risks were not calculated, since no toxicological endpoint for
cancer was selected. In residential settings, HED does not use restricted-entry intervals
or other mitigation approaches to limit postapplication exposures, because they are
viewed as impractical and not enforceable. As such, risk estimates on the day of
application are the key concern.
For the adult populations, all postapplication non-cancer risks were below HED's
level of concern, except for the 3.0 Ib a.i./A (BEAD) application rate where MOEs are 44
on day 0. For the youth populations, all postapplication non-cancer risks were below
HED's level of concern. For toddlers, postapplication non-cancer risks are not of
concern for the oral route. For the dermal route, risks to toddlers from high contact
activity on lawns exceed HED's level of concern at the 1.0/1.1 Ib a.i./A (Label) and 3.0 Ib
a.i./A (BEAD) application rates, except when 10% dermal absorption is assumed for the
granular formulations. Calculated aggregated risks to toddlers (i.e., dermal high contact
activity plus hand to mouth activity plus object to mouth activity on treated turf plus
incidental soil ingestion of pesticide residue from treated turf areas) are therefore, also of
concern, except when 10 percent dermal absorption is assumed for the granular
formulations.
6.2.6 Recommendations for Refining Residential Postapplication
Risk Assessments
In order to refine this residential assessment, data on actual use patterns including
rates, timing, and the kinds of tasks performed are required to better characterize
chlorflurenol risks.
6.3 Residential Risk Characterization
Characterization of the residential risks included in this document must consider
each of the approaches used to calculate risks as well as the information that could be
forthcoming in any probabilistic assessment that is submitted for chlorflurenol methyl
ester.
6.3.1 Characterization of Residential Handler Risks
The data that were used in the chlorflurenol residential handler assessment
represent the best data and approaches that are currently available. The inputs for
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application rate and other use/usage information (e.g., area treated and frequency of use)
used by the Agency were supported by the proposed chlorflurenol labels. There are also
many uncertainties in the assessment that are common with the occupational assessment
as well. These factors and their impacts on the results should be considered as well in the
interpretation of the results for residential handlers. Section 2.3.1 provides a summary of
these issues.
In summary, with respect to residential handler risks, the Agency believes that the
values presented in this assessment represent the highest quality results that could be
produced given the exposure, use, and toxicology data that are available.
6.3.2 Characterization of Residential Postapplication Risks
The general population can be exposed through many different pathways that
result from uses on lawns and from indoor surface treatments. To represent the wide
array of possible exposures, the Agency relies on the scenarios that have been defined in
the SOPsfor Residential Exposure Assessment and accompanying documents such as the
overview presented to the FIFRA Science Advisory Panel. For turf uses, the Agency
considered only toddlers (3 year olds) in the assessments. Toddler MOEs were calculated
for nondietary ingestion (hand-/object-to-mouth, soil ingestion and granules ingestion).
MOEs from treated indoor surfaces were also evaluated for toddlers for whom exposures
may occur from hand-to-mouth behavior.
The data that were used in the chlorflurenol residential postapplication assessment
represent the best data and approaches that are currently available. To the extent
possible, the Agency has attempted to use chlorflurenol methyl ester specific data. When
chemical-specific data were unavailable, the Agency used the current approaches for
residential assessment, many of which include recent upgrades to the SOPs. For
example, for the toddler hand-to-mouth calculations, no TTR data were available but a 5
percent transferability factor was applied to calculate residue levels appropriate for this
exposure pathway.
Finally, the Agency believes that the values presented in this assessment represent
the highest quality results that could be produced based on the currently available
postapplication exposure data. The Agency believes that the risks represent reasonable
worse-case estimates of exposure because maximum application rates are used to define
residue levels upon which the calculations are based.
7.0 OCCUPATIONAL EXPOSURE AND RISKS
7.1 Occupational Handler Exposures and Risk Estimates
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HED uses the term "handlers" to describe those individuals who are involved in
the pesticide application process. HED believes that there are distinct job functions or
tasks related to applications and that exposures can vary depending on the specifics of
each task. Job requirements (e.g., amount of chemical to be used in an application), the
kinds of equipment used, the target being treated, and the level of protection used by a
handler can cause exposure levels to differ in a manner specific to each application event.
HED uses exposure scenarios to describe the various types of handler exposures
that may occur for a specific active ingredient. The use of scenarios as a basis for
exposure assessment is very common as described in the U.S. EPA Guidelines for
Exposure Assessment (U.S. EPA; Federal Register Volume 57, Number 104; May 29,
1992). Information from the current labels, use and usage information, toxicology data,
and exposure data were all key components in the development of the exposure scenarios.
HED has developed a series of general descriptions for tasks that are associated with
pesticide applications. Tasks associated with occupational pesticide handlers are
categorized using one of the following terms:
• Mixers and/or Loaders: these individuals perform tasks in preparation for an
application. For example, prior to application, mixer/loaders would mix the
chemical and load it into the holding tank of the airplane or groundboom...
• Applicators: these individuals operate application equipment during the release
of a pesticide product into the environment. These individuals can make
applications using equipment such as airplanes or groundboom.
• Mixer/Loader/Applicators and or Loader/Applicators: these individuals are
involved in the entire pesticide application process (i.e., they do all job functions
related to a pesticide application event). These individuals would transfer the
chemical into the application equipment and then also apply it.
A chemical can produce different effects based on how long a person is exposed,
how frequently exposures occur, and the level of exposure. HED classifies exposures up
to 30 days as short-term and exposures greater than 30 days up to several months as
intermediate-term. HED completes both short- and intermediate-term assessments for
occupational scenarios in essentially all cases, because these kinds of exposures are likely
and acceptable use/usage data are not available to justify deleting intermediate-term
scenarios. Based on use data and label instructions, HED believes that occupational
chlorflurenol exposures may occur over a single day or up to weeks at a time for many
use-patterns and that intermittent exposures over several weeks also may occur. Some
applicators may apply chlorflurenol over a period of weeks, because they are custom or
commercial applicators who are completing a number of applications for a number of
different clients. Long-term handler exposures are not expected to occur for
chlorflurenol.
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Other parameters are also defined from use and usage data such as application
rates and application frequency. HED always completes non-cancer risk assessments
using maximum application rates for each in order to ensure there are no concerns for
each specific use.
Occupational handler exposure assessments are completed by HED using
different levels of risk mitigation. Typically, HED uses a tiered approach. The lowest
tier is designated as the baseline exposure scenario (i.e., long-sleeve shirt, long pants,
shoes, socks, and no respirator). If risks are of concern at baseline attire, then increasing
levels of personal protective equipment or PPE (e.g., gloves, double-layer body
protection, and respirators) are evaluated. If risks remain a concern with maximum PPE,
then engineering controls (e.g., enclosed cabs or cockpits, water-soluble packaging, and
closed mixing/loading systems) are evaluated. This approach is used to ensure that the
lowest level of risk mitigation that provides adequate protection is selected, since the
addition of PPE and engineering controls involves an additional expense to the user and -
in the case of PPE - also involves an additional burden to the user due to decreased
comfort and dexterity and increased heat stress and respiratory stress.
7.1.1 Data and Assumptions for Handler Exposure Scenarios
7.1.1.1 Assumptions for Handler Exposure Scenarios
A series of assumptions and exposure factors served as the basis for completing
the occupational handler risk assessments. Each assumption and factor is detailed below
on an individual basis. The assumptions and factors used in the risk calculations include:
• Occupational handler exposure estimates were based on surrogate data from: (1)
the Pesticide Handlers Exposure Database (PHED) and (2) the Outdoor
Residential Exposure Task Force (ORETF).
• The toxicological endpoint of concern for dermal and inhalation risks are from
studies where the effects were observed in males and females, therefore, the
average body weight of an adult male handler (i.e., 70 kg) is used to complete the
handler dermal and inhalation non-cancer risk assessment.
• The dermal absorption for liquid concentrate formulations was assumed to be
100 percent, since no dermal absorption data are available. Certain solvents in
liquid formulations can result in a high percent of dermal absorption. The
dermal absorption for granular formulation was assessed assuming both 100
percent and 10 percent, since although there are no dermal absorption data
available, it is rare for dermal absorption of a granular formulation to exceed 10
percent.
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• Generic protection factors (PFs) were used to calculate exposures when data
were not available. For example, a 50 percent protection factor was assumed for
the use of a double layer body protection.
• For non-cancer assessments, FED assumes the maximum application rates
allowed by the master labels in its risk assessments (see Tables la, Ib, Ic and 2).
• The average occupational workday is assumed to be 8 hours.
The daily areas treated were defined for each handler scenario (in appropriate
units) by determining the amount that can be reasonably treated in a single day (e.g.,
acres, square feet, or gallons per day). When possible, the assumptions for daily areas
treated are taken from the Health Effects Division Science Advisory Committee on
Exposure SOP #9: Standard Values for Daily Acres Treated in Agriculture, which was
completed on July 5, 2000. However, no standard values are available for numerous
scenarios. Assumptions for these scenarios are based on HED estimates and could be
further refined from input from affected sectors (see Tables la, Ib, and Ic)
7.1.1.2 Exposure Data for Handler Exposure Scenarios
HED uses unit exposure to assess handler exposures to pesticides. Unit exposures
are estimates of the amount of exposure to an active ingredient a handler receives while
performing various handler tasks and are expressed in terms of micrograms or milligrams
of active ingredient per pound of active ingredient handled. HED has developed a series
of unit exposures that are unique for each scenario typically considered in our
assessments (i.e., there are different unit exposures for different types of application
equipment, job functions, and levels of protection). The unit exposure concept has been
established in the scientific literature and also through various exposure monitoring
guidelines published by the U.S. EPA and international organizations such as Health
Canada and OECD (Organization for Economic Cooperation and Development). Unit
exposures were based on surrogate data from PHED and ORETF, which are described
below.
Pesticide Handler Exposure Database (PHED) Version 1.1 (August 1998):
PHED was designed by a task force of representatives from the U.S. EPA, Health
Canada, the California Department of Pesticide regulation, and member companies of the
American Crop Protection Association. PHED is a software system consisting of two
parts - a database of measured exposures for workers involved in the handling of
pesticides under actual field conditions and a set of computer algorithms used to subset
and statistically summarize the selected data. Currently, the database contains values for
over 1,700 monitored individuals (i.e., replicates).
Users select criteria to subset the PHED database to reflect the exposure scenario
being evaluated. The subsetting algorithms in PHED are based on the central
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assumption that the magnitude of handler exposures to pesticides are primarily a function
of activity (e.g., mixing/loading, applying), formulation type (e.g., liquids, granulars),
application method (e.g., aerial, groundboom), and clothing scenarios (e.g., gloves,
double layer clothing).
Once the data for a given exposure scenario have been selected, the data are
normalized (i.e., divided by) by the amount of pesticide handled resulting in standard unit
exposures (milligrams of exposure per pound of active ingredient handled). Following
normalization, the data are statistically summarized. The distribution of exposure for
each body part (e.g., chest, upper arm) is categorized as normal, lognormal, or "other"
(i.e., neither normal nor lognormal). A central tendency value is then selected from the
distribution of the exposure for each body part. These values are the arithmetic mean for
normal distributions, the geometric mean for lognormal distributions, and the median for
all "other" distributions. Once selected, the central tendency values for each body part
are composited into a "best fit" exposure value representing the entire body.
The unit exposures calculated by PHED generally range from the geometric mean
to the median of the selected data set. To add consistency and quality control to the
values produced from this system, the PHED Task Force has evaluated all data within the
system and has developed a set of grading criteria to characterize the quality of the
original study data. The assessment of data quality is based on the number of
observations and the available quality control data. These evaluation criteria and the
caveats specific to each exposure scenario are summarized in Appendix A, Table Al of
the June 30, 2006 Chlorflurenol Occupational and Residential Exposure RED. While
data from PHED provide the best available information on handler exposures, it should
be noted that some aspects of the included studies (e.g., duration, acres treated, pounds of
active ingredient handled) may not accurately represent labeled uses in all cases. HED
has developed a series of tables of standard unit exposure for many occupational
scenarios that can be utilized to ensure consistency in exposure assessments. Unit
exposures are used which represent different levels of personal protection as described
above. Protection factors were used to calculate unit exposures for varying levels of
personal protection if data were not available.
ORETF Handler Studies (MRID 449722-01): A report was submitted by the
ORETF (Outdoor Residential Exposure Task Force) that presented data in which the
application of various products used on turf by homeowners and lawncare operators
(LCOs) was monitored. All of the data submitted in this report were completed in a
series of studies. The studies relevant to the scenarios used for the chlorflurenol
assessment are described below and are summarized in Appendix A, Table Al in the
June 30, 2006, Chlorflurenol Occupational and Residential Exposure Assessment for the
RED.
OMA001: LCO Granular Applications with a Rotary Spreader (MRID 449722-01): A
loader/applicator study was performed by the Outdoor Residential Exposure Task Force
(ORETF) using Dacthal (active ingredient DCPA, dimethyl tetrachloroterephthalate) as a
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surrogate compound to determine "generic" exposures of lawn care operators (LCOs)
applying a granular pesticide formulation to residential lawns. Surrogate chemicals were
chosen by the Task Force for their representativeness based on physical chemical
properties and other factors. Dacthal, which was the surrogate chemical used for the
granular spreader studies, has a molecular weight of 331.97 and a vapor pressure of 1.6 x
10"6, and is believed to be an appropriate surrogate for many relatively nonvolatile
pesticides.
The study was designed to simulate a typical work day for a LCO applying
granular pesticide formulation to home lawns. Each LCO replicate involved loading and
applying approximately 3.3 Ib a.i. (360 Ib formulated product) over a period of about 4
hours to 15 simulated residential lawns (6480 ft2 each) with a rotary type spreader. The
average industry application rate of 2 Ib a.i./acre was simulated (actual rate achieved was
about 1.9 Ib a.i./acre). The monitoring period included driving, placing the spreader onto
and off of the truck, carrying and loading the formulation in the spreader, and the actual
application. Incidental activities such as repairs, cleaning up spills, and disposing of
empty bags were monitored. A total of 40 replicates (individual application events) were
monitored using passive dosimetry (inner and outer whole body dosimeters, hand washes,
face/neck wipes, and personal inhalation monitors with OVS tubes). The inner samples
represent a single layer of clothing. Inhalation exposure was calculated using an assumed
respiratory rate of 17 Lpm for light work (NAFTA, 1999), the actual sampling time for
each individual, and the pump flow rate. In 20 of the replicates, the subjects wore
chemical-resistant gloves while in the remaining replicates, no gloves were worn. No
gloves were worn in any replicate while driving.
All results were normalized for the amount of active ingredient handled. Nearly
all samples (for every body part and for inhalation) were above the level of quantitation
(LOQ) for dacthal. Where results were less than the reported LOQ, 1A LOQ value was
used for calculations, and no recovery corrections were applied. The overall laboratory
recoveries ranged from 83 to 101% and the field recoveries ranged from 73 to 98%. The
unit exposure values are presented in Table 15 below. [Note the inhalation exposure
value is a median because the data were found to be neither normally nor lognormally
distributed. All dermal values are geometric means as the data were lognormally
distributed.]
Table 15: Unit Exposure Values for LCO Granular Applications with a Rotary
Spreader Obtained From ORETF Studies (MRID 449722-01)
Type
LCO Granular Applications with a
Rotary Spreader
Unit Exposure
(mg exp./lb a.i. handled)
Dermal
Single Layer,
No Gloves
0.35
Single Layer,
Gloves
0.22
Double Layer2,
Gloves
0.11
Inhalation
0.0073
1 All dermal unit exposure values are geometric means. The inhalation value is a median. 2 Double layer value
calculated using a 50% protection factor.
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OMA002: LCO Spray Applications with a Low Pressure Handgun (MRID 449722-01):
A mixer/loader/applicator study was performed by the Outdoor Residential Exposure
Task Force (ORETF) using Dacthal as a surrogate compound to determine "generic"
exposures to individuals applying a pesticide to turf with a low-pressure "nozzle gun" or
"handgun" sprayer. Dermal and inhalation exposures were estimated using whole-body
passive dosimeters and breathing-zone air samples on OVS tubes. Inhalation exposure
was calculated using an assumed respiratory rate of 17 liters per minute for light work
(NAFTA, 1999), the actual sampling time for each individual, and the pump flow rate.
All results were normalized for pounds active ingredient handled.
A total of 90 replicates were monitored using 17 different subjects. Four different
formulations of dacthal [75% wettable powder (packaged in 4 and 24 pound bags), 75%
wettable powder in water soluble bags (3 pound bag), 75% water dispersible granules (2
pound bag) and 55% liquid flowable (2.5 gallon container)] were applied by five different
LCOs to actual residential lawns at each site in three different locations (Ohio, Maryland,
and Georgia) for a total of fifteen replicates per formulation. An additional ten replicates
at each site were monitored while they performed spray application only using the 75
percent wettable powder formulation. A target application rate of 2 pounds active
ingredient was used for all replicates (actual rate achieved was about 2.2 pounds active
ingredient per acre). Each replicate treated a varying number of actual client lawns to
attain a representative target of 2.5 acres (1 hectare) of turf. The exposure periods
averaged five hours twenty-one minutes, five hours thirty-nine minutes, and six hours
twenty-four minutes, in Ohio, Maryland and Georgia, respectively. Average time spent
spraying at all sites was about two hours. All mixing, loading, application, adjusting,
calibrating, and spill clean up procedures were monitored, except for typical end-of-day
clean-up activities, e.g. rinsing of spray tank, etc. Dermal exposure was measured using
inner and outer whole body dosimeters, hand washes, face/neck washes, and personal air
monitoring devices. All test subjects wore one-piece, 100 percent cotton inner
dosimeters beneath 100 percent cotton long-sleeved shirt and long pants, rubber boots
and nitrile gloves. Gloves are typically worn by most LCOs, and required by many
pesticide labels for mixing and loading.
Overall, residues were highest on the upper and lower leg portions of the
dosimeters. In general, concurrent lab spikes produced mean recoveries in the range of
78-120 percent, with the exception of OVS sorbent tube sections which produced mean
recoveries as low as 65.8 percent. Adjustment for recoveries from field fortifications
were performed on each dosimeter section or sample matrix for each study participant,
using the mean recovery for the closest field spike level for each matrix and correcting
the value to 100 percent. The unit exposure values are presented below in Table 16.
[Note the data were found to be lognormally distributed. As a result, all exposure values
are geometric means.]
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Table 16: Unit Exposure Values Obtained for LCO Spray Applications with a Low Pressure
Handgun from ORETF Handgun Studies (MRID 449722-01)
Application Method4
LCO Handgun Spray
Mixer/Loader/Applicator
Liquid Flowable
Total Dermal Unit Exposure1 (mg/lb
a.i.)
Single
Layer, No
Gloves
No Data
Single
Layer,
Gloves
0.45
Double
Layer,
Gloves 3
0.245
Inhalation Unit
Exposure1'2
(Hg/lb a.i.)
1.8
Unit exposure values reported are geometric means. Air concentration (mg/m /lb a.i.)
calculated using NAFTA '99 standard breathing rate of 17 1pm (1 mVhr).
3 Exposure calculated using OPP/HED 50% protection factor (PF) for cotton coveralls on
torso, arms, and legs.
4 All commercial handlers wore long pants, long-sleeved shirt, nitrile gloves and shoes.
OMA005: Homeowner Liquid Applications to Fruit Trees and Ornamental Plants with a
Hose-end Sprayer and a Low Pressure Handwand (MRID 445185-01):
Applications of Sevin Liquid® Carbaryl insecticide [RP-2 liquid (21%)] were
made by volunteers to two young citrus trees and two shrubs in each replicate that was
monitored in the study. The test field was located only in Florida. Twenty (20) replicates
were monitored using hose-end sprayer (Ortho® DIAL or Spray® hose end sprayer), and
20 replicates were monitored using hand held pump sprayers (low pressure handwands).
Each replicate opened the end-use product, added it to the hose-end sprayer or
hand held pump and then applied it to the trees and shrubs. After application to two trees
and two shrubs dosimeters were collected. Inhalation exposure was monitored with
personal air sampling pumps with OVS tubes attached to the shirt collar in the breathing
zone. Dermal exposure was assessed by extraction of carbaryl from inner and outer 100
percent cotton dosimeters. The inner and outer dosimeters were segmented into: lower
and upper arms, lower and upper legs, front and back torso. No gloves were worn
therefore hand exposure was assessed with 400 ml handwash with 0.01 percent Aerosol
OT-75 sodium dioctyl sulfosuccinate (OTS). One hundred percent cotton handkerchiefs
wetted with 25 ml OTS were used to wipe face and neck to determine exposure.
Field fortification recoveries for passive dosimeters averaged 88.3 percent for
inner and 76.2 percent for outer dosimeters. Face and neck wipe fortifications average
82.5 percent. Handwash and inhalation OVS tube field fortification averaged >90
percent. Inner and outer dosimeter and face and neck wipe residues were adjusted for
field fortification results. Handwash and inhalation residues were not adjusted.
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Laboratory method validation for each matrix fell within the acceptable range of
70 to 120 percent. The limit of quantitation (LOQ) was 1.0 jig/sample for all media
except the inhalation monitors where the LOQ was 0.01 jig/sample. The limit of
detection (LOD) was 0.5 jig/sample for all media except the inhalation monitors where
the LOQ was 0.005 jig/sample.
For use in reregi strati on documents, the dermal exposure was calculated by
adding the values from the hand rinses, face/neck wipes to the outer dosimeter lower legs
and lower arms plus the inner dosimeter front and rear torso, upper legs and upper arms.
This accounts for the residential handler wearing short-sleeved shirt and short pants. The
results for the low pressure handwand are summarized in Table 17 below.
The distribution of the unit exposure values is categorized as normal, lognormal,
or "other" (i.e., neither normal nor lognormal). A central tendency value is selected from
the distribution of the exposure values. These values are the arithmetic mean for normal
distributions, the geometric mean for lognormal distributions, and the median for all
"other" distributions. The dermal exposure had a lognormal distribution so the
geometric mean value was used to determine dermal exposure. The inhalation exposure
had neither a normal or lognormal distribution so the median was used to determine
inhalation exposure.
Table 17: Unit Exposure Values for Homeowner Liquid Applications to Fruit Trees and
Ornamental Plants with a Low Pressure Handwand Obtained From ORETF Study
(MRID 445185-01)
Scenario Monitored
Homeowner Liquid Applications with a Hand
Held Sprayer (Low Pressure Handwand)
Total Dermal Unit Exposure1 (mg/lb a.i.)
Short Pants,
Short Sleeves
56
Long Pants, Short
Sleeves
36
Long Pants, Long
Sleeves
30
Inhalation Unit
Exposure2
(Hg/lb a.i.)
2.6
Dermal unit exposure values reported are the geometric means.
2 Inhalation unit exposure values reported are the median values.
OMA006: Homeowner Liquid Application to Garden with a Dial type Sprayer, a Low
Pressure Handwand and a Ready-to-use Bottle (MRID 444598-01): The study was
designed to quantify dermal and inhalation exposure of homeowners as they mixed,
loaded and applied liquid formulations of a carbaryl end-use product to home garden
vegetables. A hose end sprayer and a hand held pump sprayer (low pressure handwand)
were used to apply Sevin Liquid® Brand Carbaryl Insecticide. A ready-to-use sprayer
was used to apply Sevin® Ready to Use Insect Spray. For each application method,
twenty replicates were conducted with gloves and 20 replicates were conducted without
gloves. Inhalation exposure was monitored using personal air samplers (average flow rate
of 1.5 liter/minute) and dermal exposure was monitored by using inner and outer
dosimeters, facial/neck wipes, and hand washes. The overall mean field fortification
recovery of each matrix ranged from 77.6 ± 13.6% (outer dosimeters) to 98.4 ± 3.8%
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(OVS tubes). Laboratory fortified recovery samples were analyzed with each set of
samples analyzed on a particular day; however, the results of the laboratory recoveries
were not provided in the Study Report. The results for the low pressure handwand are
summarized in Table 18 below.
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Table 18. Unit Exposure Values for Homeowner Liquid Application to Garden with a Low
Pressure Handwand Obtained From ORETF Study (MRID 444598-01)
Scenario Monitored
Homeowner Liquid Applications
with a Low Pressure Handwand
Sprayer
Total Dermal Unit Exposure1 (mg/lb a.i.)
Short Pants, Short Sleeves
Gloves
10.5
No Gloves
38
Long Pants, Short
Sleeves
Gloves
0.78
No Gloves
17
Long Pants, Long
Sleeves
Gloves
0.33
No Gloves
15
Inhalation Unit
Exposure1
Og/lba.i.)
2.7
Unit exposure
7.1.2 Occupational Handler Exposure Scenarios
It has been determined that exposure to pesticide handlers is likely during the
occupational use of chlorflurenol on agricultural crops, non-crop areas, and on turfgrass.
The anticipated use patterns and current labeling indicate occupational exposure
scenarios based on the types of equipment and techniques that can potentially be used for
chlorflurenol applications. The quantitative exposure/risk assessment developed for
occupational handlers is based on the following scenarios.
Mixer/Loaders:
(la) Mixing/loading liquids for airblast application (PHED);
(Ib) Mixing/loading liquids for ground application (PHED);
(Ic) Mixing/loading liquids to support LCO handgun applications (PHED);
(Id) Mixing/loading liquids for rights-of-way application (PHED); and
(2) Mixing/loading granules for tractor drawn spreader application (PHED).
Applicators:
(3) Applying sprays with airblast sprayer (PHED);
(4) Applying sprays with groundboom sprayer (PHED);
(5) Applying sprays with a handgun sprayer (PHED);
(6) Applying sprays with rights-of-way sprayer (PHED); and
(7) Applying granules with tractor drawn spreader (PHED).
Mixer/Loader/Applicators:
(8) Mixing/loading/applying liquids with low pressure handwand sprayer
(PHED);
(9) Mixing/loading/applying liquids with low pressure handwand sprayer (ground
directed) (ORETF);
(10) Mixing/loading/applying liquids with low pressure handwand sprayer
(overhead directed) (ORETF);
(11) Mixing/loading/applying liquids with a handgun sprayer (LCO ORETF);
(12) Mixing/loading/applying granules with a bellygrinder (PHED); and
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(13) Mixing/loading/applying granules with a push-type spreader (LCO ORETF).
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7.1.3 Non-cancer Occupational Handler Exposure and Assessment
7.1.3.1 Non-cancer Occupational Handler Exposure and Risk
Calculations
Daily Exposure: Daily dermal or inhalation handler exposures are estimated for
each applicable handler task with the application rate, the area treated in a day, and the
applicable dermal or inhalation unit exposure using the following formula:
Daily Exposure (mg a.i./day) = Unit Exposure (mg a.i./lb a.i. handled) x Application Rate
(Ibs a.i./area) x Daily Area Treated (area/day)
Where:
Daily Exposure = Amount (mg or jig a.i./day) deposited on the
surface of the skin that is available for dermal
absorption or amount inhaled that is available for
inhalation absorption;
Unit Exposure = Unit exposure value (mg or jig a.i./lb a.i.)
derived from August 1998 PHED data or from
ORETF data;
Application Rate = Normalized application rate based on a
logical unit treatment, such as acres, square feet, or
gallons. Maximum values are generally used (Ib
a.i./A, Ib a.i./sq ft, Ib a.i./gal); and
Daily Area Treated = Normalized application area based on a logical unit
treatment such as acres (A/day), square feet (sq
ft/day), gallons per day (gal/day).
Daily Dose: The daily dermal or inhalation dose is calculated by normalizing the
daily exposure by body weight and adjusting, if necessary, with an appropriate dermal or
inhalation absorption factor. For all dermal and inhalation exposure, an average male and
female body weight of 70 kilograms was used, since the toxicological endpoint is not
sex-specific. 100% absorption was used for inhalation exposures. Dermal exposure was
assessed assuming 100% dermal absorption for liquid formulations and both 100% and
10% dermal absorption for granular formulations. Daily dose was calculated using the
following formula:
Average Daily Dose (mg/kg/day) = Daily Exposure (mg a.i./day) x (Absorption Factor
(%/100) / Body Weight (kg)
Where:
104
-------
Average Daily Dose = Absorbed dose received from exposure to a
pesticide in a given scenario (mg pesticide
active ingredient/kg body weight/day);
Daily Exposure = Amount (mg a.i./day) deposited on
the surface of the skin that is available for
dermal absorption or amount inhaled that is
available for inhalation absorption;
Absorption Factor = A measure of the amount of chemical that
crosses a biological boundary such as the
skin or lungs (% of the total available
absorbed); and
Body Weight = Body weight determined to represent the
population of interest in a risk assessment
(kg).
Margins of Exposure: Non-cancer dermal and inhalation risks for each
applicable handler scenario are calculated using a Margin of Exposure (MOE), which is a
ratio of the toxicological endpoint of concern to the daily dose. All MOE values were
calculated separately for dermal and inhalation exposure levels using the formula below:
MOE= NOAEL or LOAEL (mg/kg/day) / Average Daily Dose (mg/kg/day)
Where:
MOE = Margin of Exposure, value used by HED to
represent risk or how close a chemical exposure is
to being a concern (unitless);
ADD = Average Daily Dose or the absorbed dose received
from exposure to a pesticide in a given scenario (mg
pesticide active ingredient/kg body weight/day);
and
NOAEL or LOAEL = Dose level in a toxicity study, where no observed
adverse effects (NOAEL) or where the lowest
observed adverse effects (LOAEL) occurred in the
study
Risk values are presented for each route of exposure (i.e., dermal or inhalation) in
each scenario, because risk mitigation measures are specific to the route of exposure. A
total MOE was also calculated because the dermal and inhalation toxicological endpoints
of concern are based on the same adverse effects. The total MOE values were calculated
using the formula below:
Total MOE = (II (II Dermal MOE) + (I/Inhalation MOE))
105
-------
7.1.3.2 Occupational Non-cancer Risk Summary (using PHED
and ORETF data)
Table 19 presents the risk assessments for short and intermediate-term dermal and
inhalation exposures at baseline, with additional personal protective equipment, and with
engineering controls. All of the risk calculations for occupational chlorflurenol handlers
completed in this assessment are included in Appendix B of the Mayl3, 2006
Chlorflurenol Occupational and Residential Exposure RED..
106
-------
Table 19. Occupational Handler Short-and Intermediate-term Dermal, Inhalation and Total Exposure and Risks
Exposure
Scenario
Crop or
Target
App Rate
Area
Treated
Daily
MOEs (Level of Concern = 100)
Dermal
Baseline
(unless
indicated
otherwise)
PPE-G,
SL:
Single
layer
w/gloves
PPE-G,
DL:
Double
layer w/
gloves
Inhalation
Baseline
(unless
indicated
otherwise)
Total
Dermal +
Baseline
Inh.
(unless
indicated
otherwise)
PPE-G,
SL
Dermal
Baseline
Inh
PPE-G,
DL
Dermal
Baseline
Inh
Mixer/Loader
la) Mixing/
Loading Liquids
Concentrates for
Airblast
Applications
(PHED)
Ib) Mixing/
Loading Liquids
Concentrates for
Groundboom
Applications
(PHED)
Ic) Mixing/
Loading Liquid
Concentrates to
Support LCO
Handgun
Applications
(mixing/loading
supports 20
LCDs) (PHED)
Pineapple
Pineapple
Turf: Golf
Course
Lawn and
Ornamental
Turf
(including
golf course)
1.0 Ib
a.i./A
(Label &
BEAD)
1.0 Ib
ai/A
(Label &
BEAD)
1.0 Ib
a.i./A
(Label)
3.0 Ib
a.i./A
(BEAD)
1.0 Ib
a.i./A
(Label)
3.0 Ib
a.i./A
(BEAD)
40
acres
80
acres
40
acres
40
acres
100
acres
100
acres
19
9.4
19
6.2
7.5
2.5
2,400
1,200
2,400
790
940
310
3,200
1,600
3,200
1,100
1,300
430
45,000
23,000
45,000
15,000
18,000
6000
19
9.3
19
6.2
7.5
2.5
2,200
1,100
2,200
750
900
300
3,000
1,500
3,000
990
1,200
400
107
-------
Table 19. Occupational Handler Short-and Intermediate-term Dermal, Inhalation and Total Exposure and Risks
Exposure
Scenario
Id) Mixing/
Loading Liquid
Concentrates to
Support Rights
ofWay(PHED)
Crop or
Target
Gymnosperms
Hardwoods,
Hedges, Vines
Non-
agricultural
rights-of-
ways/fence
rows and
hedge rows
Turf:
growing in
culverts,
ROW, median
strip, ditches
Shrubs, Shade
Trees, and
Vines
Hedges, Vines
High density
Forestry
Vegetation
App Rate
0.0025 Ib
a.i./gal
(Label)
51b
a.i./acre
(BEAD)
0.01 Ib
a.i./gal
(Label)
51b
a.i./acre
(BEAD)
3.0 Ib
a.i./A
(Label &
BEAD)
3.0 Ib
ai/A
(Label &
BEAD)
4.5 Ib
a.i./A
(BEAD)
0.01 Ib
a.i./gallon
(Label)
4.0 Ib
a.i./A
(BEAD)
Area
Treated
Daily
1,000
gal
80
acres
1 000
gdl
80
acres
80
acres
80
acres
acres
80
acres
80
acres
MOEs (Level of Concern = 100)
Dermal
Baseline
(unless
indicated
otherwise)
300
1.9
75
1.9
3.1
3.1
2.1
75
2.3
PPE-G,
SL:
Single
layer
w/gloves
38,000
240
9,400
240
390
390
260
9,400
290
PPE-G,
DL:
Double
layer w/
gloves
51,000
320
13,000
320
530
530
350
13,000
400
Inhalation
Baseline
(unless
indicated
otherwise)
720,000
4,500
180,000
4,500
7,500
7,500
5,000
180,000
5,700
Total
Baseline
Dermal +
Baseline
Inh.
(unless
indicated
otherwise)
300
1.9
75
1.9
3.1
3.1
2.1
75
2.3
PPE-G,
SL
Dermal
Baseline
Inh
36,000
220
9,000
220
370
370
250
9,000
280
PPE-G,
DL
Dermal
Baseline
Inh
48,000
300
12,000
300
500
500
330
12,000
370
108
-------
Table 19. Occupational Handler Short-and Intermediate-term Dermal, Inhalation and Total Exposure and Risks
Exposure
Scenario
2) Mixing/
Loading
Granules for
Tractor Drawn
Spreader
Application
(PHED)
Crop or
Target
Lawns and
Ornamental
Turf
(including
golf course)
Lawns and
Ornamental
Turf
(including
golf course)
App Rate
l.llb
a.i./A
(Label -
100%
DA)
l.llb
a.i./A
(Label -
10% DA)
3.0 Ib
a.i./A
(BEAD-
100%
DA)
3.0 Ib
ai/A
(BEAD -
10% DA)
Area
Treated
Daily
acres
40
acres
40
acres
40
acres
MOEs (Level of Concern = 100)
Dermal
Baseline
(unless
indicated
otherwise)
5,900
59,000
2,200
22,000
PPE-G,
SL:
Single
layer
w/gloves
7,100
71,000
2,600
26,000
PPE-G,
DL:
Double
layer w/
gloves
15,000
150,000
5,300
53,000
Inhalation
Baseline
(unless
indicated
otherwise)
29,000
29,000
11,000
11,000
Total
Baseline
Dermal +
Baseline
Inh.
(unless
indicated
otherwise)
4,900
19,000
1,800
7,100
PPE-G,
SL
Dermal
Baseline
Inh
5,700
21,000
2,100
7,600
PPE-G,
DL
Dermal
Baseline
Inh
9,700
24,000
3,500
8,900
Applying
3) Applying
Sprays via
Airblast
Equipment
(PHED)
4) Applying
Sprays via
Groundboom
Equipment
(PHED)
Pineapple
Pineapple
Turf: Golf
Course
1 0 Ib
a i /A
(Label &
BEAD)
1.0 Ib
a i /A
(Label &
BEAD)
.0 Ib
a.i./A
(Label)
3.0 Ib
a.i./A
(BEAD)
40
acres
80
acres
40
acres
40
acres
150
1,900
3,900
1,300
230
1,900
3,900
1,300
250
2,500
4,900
1,600
12,000
37,000
73,000
24,000
150
1,800
3,700
1,200
220
1,800
3,700
1,200
240
2,300
4,600
1,500
109
-------
Table 19. Occupational Handler Short-and Intermediate-term Dermal, Inhalation and Total Exposure and Risks
Exposure
Scenario
5) Applying
Sprays via
Handgun
Equipment
(PHED)
6) Applying
Sprays via
Rights of Way
Equipment
(PHED)
Crop or
Target
Lawn and
Ornamental
Turf
(including
golf course)
Gymnosperms
Non-
agricultural
rights-of-
ways/fence
rows and
hedge rows
Turf:
growing in
culverts,
ROW, median
strip, ditches
Shrubs, Shade
Trees and
Vines
Hedges and
Vines
App Rate
1.0 Ib
a.i./A
(Label)
3.0 Ib
a.i./ A
(BEAD)
0.0025 Ib
a.i./gal
(Label)
5 Ib a i /A
(BEAD)
0.01 Ib
a.i./gal
(Label)
5.0 Ib
a.i./A
(BEAD)
3.0 Ib
a.i./A
(Label &
BEAD)
3.0 Ib
ai/A
(Label &
BEAD)
4.5 Ib
a.i./A
(BEAD)
0 01 Ib
a.i./gallon
(Label)
Area
Treated
Daily
5 acres
5 acres
1 000
gdi
80
acres
40 gal
80
acres
80
acres
80
acres
80
acres
1000
gal
MOEs (Level of Concern = 100)
Dermal
Baseline
(unless
indicated
otherwise)
No Data
No Data
670
4.2
170
4.2
7.0
7.0
4.6
170
PPE-G,
SL:
Single
layer
w/gloves
1,300
430
2,200
14
560
14
23
23
15
560
PPE-G,
DL:
Double
layer w/
gloves
2,300
760
3,000
19
750
19
31
31
21
750
Inhalation
Baseline
(unless
indicated
otherwise)
310,000
100,000
220,000
1,400
56,000
1,400
2,300
2,300
1,500
56,000
Total
Baseline
Dermal +
Baseline
Inh.
(unless
indicated
otherwise)
No Data
No Data
670
4.2
170
4.2
6.9
6.9
4.6
170
PPE-G,
SL
Dermal
Baseline
Inh
1,300
420
2,200
14
550
14
23
23
15
550
PPE-G,
DL
Dermal
Baseline
Inh
2,300
760
3,000
18
740
18
31
31
21
740
110
-------
Table 19. Occupational Handler Short-and Intermediate-term Dermal, Inhalation and Total Exposure and Risks
Exposure
Scenario
7) Applying
granules with
tractor drawn
(PHED)
Crop or
Target
High Density
Forestry
Management
Lawns and
Ornamental
Turf
(including
golf course)
App Rate
4 Ib a.i./A
(BEAD)
l.llb
a.i./A
(Label -
100%
DA)
l.llb
a.i./A
(Label -
10% DA)
3.0 Ib
a.i./A
(BEAD-
100%
DA)
3.0 Ib
a.i./A
(BEAD-
10% DA)
Area
Treated
Daily
80
acres
40
acres
40
acres
40
acres
40
acres
MOEs (Level of Concern = 100)
Dermal
Baseline
(unless
indicated
otherwise)
5.2
5,000
50,000
1,800
18,000
PPE-G,
SL:
Single
layer
w/gloves
17
6,800
68,000
2,500
25,000
PPE-G,
DL:
Double
layer w/
gloves
23
12,000
120,000
4,300
43,000
Inhalation
Baseline
(unless
indicated
otherwise)
1,700
41,000
41,000
15,000
15,000
Total
Baseline
Dermal +
Baseline
Inh.
(unless
indicated
otherwise)
5.2
4,400
4,400
1,600
8,300
PPE-G,
SL
Dermal
+
Baseline
Inh.
17
5,900
26,000
2,200
9,400
PPE-G,
DL
Dermal
+
Baseline
Inh.
23
9,100
30,000
3,300
11,000
Mixing/Loading/Applying
8) Mixing/
Loading/
Applying Liquid
Concentrates
with Low
Pressure
Handwand
(PHED)
Lawns and
Ornamental
Turf
(including
golf course)
Gymnosperms
Hardwoods,
Hedges, Vines
1.0 Ib
a.i./A
(Label)
3.0 Ib
a.i./A
(BEAD)
0.0025 Ib
a.i./gal
(Label)
5.0 Ib a/A
(BEAD)
0.01 Ib
a.i./gal
5 acres
5 acres
40 gal
5 acres
40 gal
4.3
1.4
220
0.87
54
1,000
340
50,000
200
13,000
1,200
390
59,000
230
15,000
14,000
4,800
720,000
2,900
180,000
4.3
1.4
220
0.87
54
940
310
47,000
190
12,000
1,100
360
54,000
220
14,000
111
-------
Table 19. Occupational Handler Short-and Intermediate-term Dermal, Inhalation and Total Exposure and Risks
Exposure
Scenario
Crop or
Target
Non-
agricultural
rights-of-
ways/fence
rows and
hedge rows
Turf:
growing in
culverts,
ROW, median
strip, ditches
Shrubs, Shade
Trees and
Vines
Hedges, Vines
Trees- bark
banding
Ornamental
Trees
High Density
Forestry
Vegetation
App Rate
5 0 Ib a/A
(BEAD)
3.0 Ib
a.i./A
(Label &
BEAD)
3.0 Ib
ai/A
(Label &
BEAD)
4.5 Ib
a.i./A
(Label &
BEAD)
0.01 Ib
a.i./gallon
(Label)
0 083 Ib
a.i./gal
(Label)
2.5 Ib
a.i./A
(BEAD)
4.0 Ib
a.i./A
(BEAD)
Area
Treated
Daily
5 acres
5 acres
5 acres
5 acres
40 gal
40 gal
5 acres
5 acres
MOEs (Level of Concern = 100)
Dermal
Baseline
(unless
indicated
otherwise)
0.87
1.4
1.4
0.96
54
6.5
1.7
1.1
PPE-G,
SL:
Single
layer
w/gloves
200
340
340
220
13,000
1,500
400
250
PPE-G,
DL:
Double
layer w/
gloves
230
390
390
260
15,000
1,800
470
290
Inhalation
Baseline
(unless
indicated
otherwise)
2,900
4,800
4,800
3,200
180,000
22,000
5,800
3,600
Total
Baseline
Dermal +
Baseline
Inh.
(unless
indicated
otherwise)
0.87
1.4
1.4
0.96
54
6.5
1.7
1.1
PPE-G,
SL
Dermal
Baseline
Inh
190
310
310
210
12,000
1,400
380
240
PPE-G,
DL
Dermal
Baseline
Inh
220
360
360
240
14.000
1,600
430
270
112
-------
Table 19. Occupational Handler Short-and Intermediate-term Dermal, Inhalation and Total Exposure and Risks
Exposure
Scenario
9) Mixing/
Loading/
Applying Liquid
Concentrates
with Low
Pressure
Handwand -
Ground Directed
(ORETF OMA
006)
Crop or
Target
Lawns and
Ornamental
Turf
(including
golf course)
Non-
agricultural
rights-of-
ways/fence
rows and
hedge rows
Turf:
growing in
culverts,
ROW, median
strip, ditches
Shrubs, Shade
Trees, and
Vines
Hedges
Trees- bark
banding
App Rate
lOlb
a.i./A
(Label)
3.0 Ib
a.i./A
(BEAD)
3 0 Ib
a.i./A
(BEAD)
3.0 Ib
a.i./A
(BEAD)
4.5 Ib
a.i./A
(BEAD)
0.01 Ib
a.i./gal
(Label)
0 083 Ib
a.i./gal
(Label)
Area
Treated
Daily
5 acres
5 acres
5 acres
5 acres
5 acres
40 gal
40 gal
MOEs (Level of Concern = 100)
Dermal
Baseline
(unless
indicated
otherwise)
29
9.6
9.6
9.6
6.4
360
44
PPE-G,
SL:
Single
layer
w/gloves
1,300
440
440
440
290
16,000
2,000
PPE-G,
DL:
Double
layer w/
gloves
No
Data
No
Data
No
Data
Mr>
Data
No
Data
No
Data
No
Data
Inhalation
Baseline
(unless
indicated
otherwise)
160,000
54,000
54,000
54,000
36,000
2,000,000
240,000
Total
Dermal +
Baseline
Inh.
(unless
indicated
otherwise)
29
9.6
9.6
9.6
6.4
360
44
PPE-G,
SL
Dermal
Baseline
Inh
1,300
430
430
430
290
16,000
2,000
PPE-G,
DL
Dermal
Baseline
Inh
No Data
No Data
No Data
No Data
No Data
No Data
No Data
113
-------
Table 19. Occupational Handler Short-and Intermediate-term Dermal, Inhalation and Total Exposure and Risks
Exposure
Scenario
10) Mixing/
Loading/
Applying Liquid
Concentrates
with Low
Pressure
Handwand -
Overhead
Directed
(ORETF OMA
005)
Crop or
Target
Gymnosperms
Hardwoods
Vines
Shade Trees
and Vines
Ornamental
Trees
High Density
Forestry
Vegetation
App Rate
0.0025 Ib
a.i./gal
(Label)
5 Ib a i /A
(BEAD)
0.01 Ib
a.i./gal
(Label)
5.0 Ib
a.i./A
(BEAD)
0.01 Ib
a.i./gallon
(Label)
4.5 Ib
a.i./A
(BEAD)
2.5 Ib
a.i./A
(BEAD)
4 Ib a i /A
(BEAD)
Area
Treated
Daily
40 gal
5 acres
40 gal
5 acres
40 gal
5 acres
5 acres
5 acres
MOEs (Level of Concern = 100)
Dermal
Baseline
(unless
indicated
otherwise)
720
2.9
180
2.9
180
3.2
5.8
3.6
PPE-G,
SL:
Single
layer
w/gloves
No Data
No Data
No Data
No Data
No Data
No Data
No Data
No Data
PPE-G,
DL:
Double
layer w/
gloves
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
Inhalation
Baseline
(unless
indicated
otherwise)
5,700,000
33,000
2,100,000
33,000
2,100,000
37,000
67,000
42,000
Total
Dermal +
Baseline
Inh.
(unless
indicated
otherwise)
720
2.9
180
2.9
180
3.2
5.8
3.6
PPE-G,
SL
Dermal
Baseline
Inh
No data
No Data
No Data
No Data
No Data
No Data
No Data
No Data
PPE-G,
DL
Dermal
Baseline
Inh
No data
No Data
No Data
No Data
No Data
No Data
No Data
No Data
114
-------
Table 19. Occupational Handler Short-and Intermediate-term Dermal, Inhalation and Total Exposure and Risks
Exposure
Scenario
11) Mixing/
Loading/
Applying Liquid
Concentrates
with a Handgun
Sprayer (LCD
ORETF data
OMA 002)
Crop or
Target
Lawn and
Ornamental
Turf
Gymnosperms
Hardwoods
App Rate
1.0 Ib
a.i./A
(Label)
3.0 Ib
a.i./A
(BEAD)
0.0025 Ib
a.i./gal
(Label)
5.0 Ib
a.i./A
(BEAD)
0.01 Ib
a.i./gal
(Label)
5.0 Ib
a.i./A
(BEAD)
Area
Treated
Daily
5 acres
5 acres
1,000
gal
5 acres
1,000
gal
5 acres
MOEs (Level of Concern = 100)
Dermal
Baseline
(unless
indicated
otherwise)
No Data
No Data
No Data
No Data
No Data
No Data
PPE-G,
SL:
Single
layer
w/gloves
960
320
1,900
190
480
190
PPE-G,
DL:
Double
layer w/
gloves
1,800
590
3,500
350
890
350
Inhalation
Baseline
(unless
indicated
otherwise)
240,000
80,000
480,000
48,000
120,000
48,000
Total
Baseline
Dermal +
Baseline
Inh.
(unless
indicated
otherwise)
No Data
No Data
No Data
No Data
No Data
No Data
PPE-G,
SL
Dermal
+
Baseline
Inh.
960
320
1,900
190
480
190
PPE-G,
DL
Dermal
+
Baseline
Inh.
1,800
590
3,500
350
880
350
115
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Table 19. Occupational Handler Short-and Intermediate-term Dermal, Inhalation and Total Exposure and Risks
Exposure
Scenario
11) Mixing/
Loading/
Applying Liquid
Concentrates
with a Handgun
Sprayer (LCO
ORETF data
OMA 002)
(cont.)
12) Mixing/
loading/applying
granules with a
belly grinder
(PHED)
Crop or
Target
Non-
agricultural
rights-of-
ways/fence
rows and
hedge rows
Turf:
growing in
culverts,
ROW, median
strip, ditches
Shrubs, Shade
Trees Vines
Hedges, Vines
Ornamental
Trees
High density
Forestry
Vegetation
Lawns and
Ornamental
Turf
(including
golf course)
App Rate
3.0 Ib
a.i./A
(Label &
BEAD)
3.0 Ib
a.i./A
(Label &
BEAD)
4.5 Ib
a.i./A
(BEAD)
0.01 Ib
a.i./gallon
(Label)
2.5 Ib
a.i./A
(BEAD)
4.0 Ib
a.i./A
(BEAD)
l.llb
a.i./A
(Label -
100%
DA)
l.llb
a.i./A
(Label -
10% DA)
Area
Treated
Daily
5 acres
5 acres
5 acres
5 acres
5 acres
5 acres
1 acre
1 acre
MOEs (Level of Concern = 100)
Dermal
Baseline
(unless
indicated
otherwise)
No Data
No Data
No Data
No Data
No Data
No Data
200
2,000
PPE-G,
SL:
Single
layer
w/gloves
320
320
210
480
390
240
210
2,100
PPE-G,
DL:
Double
layer w/
gloves
590
590
390
890
710
440
350
3,500
Inhalation
Baseline
(unless
indicated
otherwise)
80,000
80,000
54,000
120,000
96,000
60,000
32,000
32,000
Total
Dermal +
Baseline
Inh.
(unless
indicated
otherwise)
No Data
No Data
No Data
No Data
No Data
No Data
200
1,900
PPE-G,
SL
Dermal
Baseline
Inh
320
320
210
480
380
240
210
2,000
PPE-G,
DL
Dermal
Baseline
Inh
590
590
390
880
700
440
340
3,100
116
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Table 19. Occupational Handler Short-and Intermediate-term Dermal, Inhalation and Total Exposure and Risks
Exposure
Scenario
12) Mixing/
loading/applying
granules with a
belly grinder
(PHED) (cont.)
13) Mixing/
loading/applying
granules with a
push-type
spreader (LCO
ORETF OMA
001)
Crop or
Target
Lawns and
Ornamental
Turf
(including
golf course)
Lawns and
Ornamental
Turf
(including
golf course)
App Rate
3.0 Ib
a.i./A
(BEAD-
100%
DA)
3 0 Ib
ai/A
(BEAD-
10% DA)
l.llb
a.i./A
(Label -
100%
DA)
1 1 Ib
ai/A
(Label -
10% DA)
3.0 Ib
a.i./A
(BEAD-
100%
DA)
3.0 Ib
a.i./A
(BEAD-
10% DA)
Area
Treated
Daily
5 acres
5 acres
5 acres
5 acres
5 acres
5 acres
MOEs (Level of Concern = 100)
Dermal
Baseline
(unless
indicated
otherwise)
72
720
1,100
110,000
410
41,000
PPE-G,
SL:
Single
layer
w/gloves
78
780
1,800
180,000
660
66,000
PPE-G,
DL:
Double
layer w/
gloves
130
1,300
3,600
36,000
1,300
13,000
Inhalation
Baseline
(unless
indicated
otherwise)
12,000
12,000
54,000
54,000
20,000
20,000
Total
Baseline
Dermal +
Baseline
Inh.
(unless
indicated
otherwise)
72
680
1,100
9,300
400
3,400
PPE-G,
SL
Dermal
Baseline
Inh
77
730
1,700
13,000
640
4,900
PPE-G,
DL
Dermal
Baseline
Inh
130
1,100
3,400
22,000
1,200
7,900
7.1.4 Cancer Occupational Handler Exposure and Risk Assessment
No cancer endpoints of concern for chlorflurenol were identified; therefore cancer
risks to handlers were not assessed.
117
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7.1.5 Summary of Risk Concerns and Data Gaps for Occupational
Handlers
7.1.5.1 Summary of Risk Concerns
For dermal and inhalation exposures (short- and intermediate-term), the level of
concern or target MOE is 100. The calculated dermal and inhalation risks were
combined for short-term and for intermediate-term because the dermal and inhalation
endpoints were based on the same toxicological effects.
For all occupational scenarios, the inhalation risks were below HED's level of
concern at the baseline level.
For all occupational scenarios, the dermal risks were below FtED's level of
concern at some level of mitigation for all occupational scenarios except applying liquid
sprays using rights-of-way equipment:
• to turf growing in culverts, rights of way, median strips, ditches, and/or under
security fences at the 3 Ib a.i./A rate (Label & BEAD) and 80 acres per day - the
baseline dermal MOE was 7.0 and with the highest dermal mitigation level
(double layer clothing with gloves), the dermal MOE and the total MOE (dermal
plus inhalation) is 31;
• to non-agricultural rights-of-ways/fence rows and hedge rows at the 3 Ib a.i./A
rate (Label & BEAD) and 80 acres per day — the baseline dermal MOE was 7.0
and with the highest dermal mitigation level (double layer clothing with gloves),
the dermal MOE and the total MOE (dermal plus inhalation) is 31;
• to gymnosperms at the 5 Ib a.i./A rate (BEAD) and 80 acres per day — the
baseline dermal MOE was 4.2 and with the highest dermal mitigation level
(double layer clothing with gloves), the dermal MOE and the total MOE (dermal
plus inhalation) is 18;
• to shrubs, shade trees, and vines at the 4.5 Ib a.i./A rate (BEAD) and 80 acres per
day — the baseline dermal MOE was 4.6 and with the highest dermal mitigation
level (double layer clothing with gloves), the dermal MOE and the total MOE
(dermal plus inhalation) is 21; and
• to high density forestry management at the 4.0 Ib a.i./A rate (BEAD) and 80 acres
per day - the baseline dermal MOE was 5.2 and with the highest dermal
mitigation level (double layer clothing with gloves), the dermal MOE and the
total MOE (dermal plus inhalation) is 23.
For the following scenarios, the dermal and total risks were of concern at baseline level
of mitigation, but were not a concern with single layer clothing plus gloves):
• mixing/loading liquid concentrates for all scenarios, except mixing/loading liquid
concentrates to support rights-of-way applications to gymnosperms at the 0.0025
Ib a.i./gal (label) application rate - these dermal risks were not of concern at
118
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baseline;
• mixing/loading/applying liquid concentrates with low pressure handwand (PHED
data) for all scenarios, except applications to gymnosperms at the 0.0025 Ib
a.i./gal (label) application rate - these dermal risks were not of concern at
baseline;
• mixing/loading/applying liquid concentrates with low pressure handwand (ground
directed ORETF data), for all scenarios except applications to hedges at the 0.01
Ib a.i./gal (Label) application rate - these dermal risks were not of concern at
baseline; and
• mixing/loading/applying liquid concentrates with low pressure handwand
(upward directed ORETF data), for all scenarios except applications to hardwoods
and vines at the 0.01 Ib a.i./gal (Label) application rate and applications to
gymnosperms at the 0.0025 Ib a.i./gal (label) application rate - these dermal risks
were not of concern at baseline.
For the following scenario, the dermal and total risks were of concern at baseline
and single layer plus gloves levels of mitigation, but were not a concern with double layer
body protection plus chemical-resistant gloves: loading/applying granular formulations
with a bellygrinder (PHED data) for the 3.0 Ib a.i./A (BEAD) application rate and
assuming 100% dermal absorption
There are no data to assess baseline dermal risks for application via handgun
equipment and mixing/loading/applying via handgun equipment. Dermal risks are below
HED's level of concern for handlers of these scenarios when personal protective
equipment (i.e., single layer clothing plus gloves) is considered.
7.1.5.2 Summary of Data Gaps
There are no data gaps associated with the occupational handler scenarios.
7.1.6 Recommendations for Refining Occupational Handler Risk
Assessment
In order to refine this occupational risk assessment, data on actual use patterns
including rates, timing, and areas treated would better characterize chlorflurenol methyl
ester risks. Exposure studies for many equipment types that lack data or that are not well
represented in PHED or ORETF (e.g., because of low replicate numbers or data quality)
should also be considered based on the data gaps identified above and based on a review
of the quality of the data used in this assessment.
7.2 Occupational Postapplication Exposures and Non-Cancer Risk
Estimates
119
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HED uses the term "postapplication" to describe exposures to individuals that
occur as a result of being in an environment that has been previously treated with a
pesticide (also referred to as reentry exposure). HED believes that there are distinct job
functions or tasks related to the kinds of activities that occur in previously treated areas.
Job requirements (e.g., the kinds of jobs to cultivate a crop), the nature of the crop or
target that was treated, and how the chemical residues degrade in the environment can
cause exposure levels to differ over time. Each factor has been considered in this
assessment.
7.2.1 Occupational Postapplication Exposure Scenarios
Currently, chlorflurenol uses are varied as it can be used on agricultural crops (i.e.
pineapple) and in a variety of other outdoor occupational settings (i.e., rights-of-way, golf
course turf). As a result, a wide array of individuals can potentially be exposed by
working in areas that have been previously treated. HED is concerned about the kinds of
exposures one could receive in the workplace.
HED uses a concept known as the transfer coefficient to numerically represent the
postapplication exposures one would receive (generally presented as cm2/hour). The
transfer coefficient concept has been established in the scientific literature and through
various exposure monitoring guidelines published by the U.S. EPA and international
organizations such as Health Canada and the Organization for Economic Cooperation and
Development. The establishment of transfer coefficients also forms the basis of the work
of the Agricultural Reentry Task Force. A transfer coefficient is a measure of the residue
transferred from a treated surface to a person who is doing a task or activity in a treated
area. These values are the ratio of an exposure for a given task or activity to the amount
of pesticide residue on treated surfaces available for transfer. HED has developed a series
of standard transfer coefficients that are unique for variety of job tasks or activities that
are used in lieu of chemical- and scenario-specific data.
To develop a postapplication assessment, HED considers the types of tasks and
activities that individuals are likely to be doing in areas recently treated with a pesticide.
For consistency within postapplication assessments, HED has developed a list of tasks
commonly associated with specific crops or use-patterns, which are likely to result in
postapplication exposures. Postapplication pesticide exposures that result from an
individual's employment are considered occupational exposures. Common examples
include: crop maintenance tasks (e.g., irrigating, weeding, and mowing) and crop advisor
tasks (e.g., scouting).
HED considers how and when a pesticide is applied to estimate the level of
transferable residues to which individuals could be exposed over time. Label directions
and other use data are considered to determine application rates and application
frequency. HED completes non-cancer postapplication risk assessments using maximum
application rates for each scenario. When postapplication non-cancer risks are a concern
120
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using maximum application rates, HED may also consider typical application rates or
application frequency, to further evaluate the overall risks associated with the use of the
pesticide. To estimate the amount of transferable residues on a treated surface, HED
uses, when possible, chemical- and crop-specific studies as described in HED guidelines
for exposure data collection (Series 875, Occupational and Residential Exposure Test
Guidelines: Group B - Postapplication Exposure Monitoring Test Guidelines). For
postapplication exposures, unique techniques are used to measure the amount of pesticide
residue on a treated surface available for possible transfer. These techniques are distinct
from those which measure total pesticide residue on a treated surface and absorbed into a
treated entity. When appropriate chemical- and crop-specific transferable residue data are
unavailable, HED also has developed a standard modeling approach to predict
transferable residues over time (best described in HED's SOPs for Residential Exposure
Assessment). All agricultural occupational postapplication scenarios (i.e. pineapple) were
evaluated using HED's default assumptions that 20 percent of the initial application is
available for transfer on day 0 (i.e., 12 hours after application) and that the residue
dissipates at a rate of 10 percent per day. All commercial occupational postapplication
scenarios (i.e. lawn and turf) were evaluated using HED's default assumptions that 5
percent of the initial application is available for transfer on day 0 (i.e., 12 hours after
application) and that the residue dissipates at a rate of 10 percent per day.
HED also must consider the likely frequency and duration of postapplication
occupational exposures to chlorflurenol. Short-term (30 days) always are considered in
these assessments. Intermediate-term (greater than 30 days to several months) exposure
durations are appropriate for postapplication occupational exposures scenarios where the
pesticide is reapplied several times over a growing season, or the pesticide residues
persist for relatively long periods of time, or the crop or use-pattern is such that
occupational postapplication workers may be exposed to several different treated areas in
the course of their work. For example, migrant and seasonal workers may move from
farm to farm and be exposed several weeks to several months or different fields or
greenhouses on an individual establishment may be treated over a period of weeks due to
differing levels of infestation or staggered crop cycles. For chlorflurenol, the exposure
durations for non-cancer postapplication risk assessment were short-term (30 days) and
intermediate-term (greater than 30 days up to several months). However, since the
dermal toxicological endpoint of concern is the same for short- and intermediate-term
exposures, the short- and intermediate-term postapplication risks are numerically
identical.
Inhalation exposures are thought to be negligible in outdoor postapplication
scenarios, since chlorflurenol has low vapor pressure and the dilution factor outdoors is
considered infinite.
HED has used the basic approach described above since the mid 1980s for
calculating postapplication risks to pesticides. From that time to the present, several
revisions and modifications were made to Agency policies as data, which warranted such
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changes, became available. In 1995, the Agency issued a Data Call-In for postapplication
agricultural data that prompted the formation of the Agricultural Reentry Task Force
(ARTF). This task force has generated a number of exposure studies and associated
documents that are currently under review. The work of the ARTF is not yet complete;
however, sufficient data were available from the group that warranted a significant
interim change in Agency policy related to the data which were already available as the
efforts of the ARTF paralleled a push for tolerance reassessment stipulated by the
timelines established by FQPA. As a result of the need for the revision and using the
latest data, the Agency developed a revised policy on August 7, 2000 entitled Policy
003.1 Science Advisory Council for Exposure Policy Regarding Agricultural Transfer
Coefficients. The revision to this policy entailed linking worker activities to more
specific crop/agronomic groupings and making better use of the available occupational
postapplication exposure data. In the new policy, transfer coefficients were selected to
represent the activities associated with 18 distinct crop/agronomic groupings based on
different types of vegetables, trees, berries, vine/trellis crops, turf, field crops, and
bunch/bundle crops (e.g., tobacco).
Within each agronomic group, a variety of cultural practices are required to
maintain the included crops. These practices are varied and typically involve light to
heavy contact with immature plants as well as with more mature plants. HED selected
transfer coefficient values in its revision of Policy 003 to represent this range of
exposures within each agronomic group. In the policy, transfer coefficients were placed
in 1 of 5 generic categories based on the exposures relative to that group. These 5
categories include: very low exposure, low exposure, medium exposure, high exposure,
and very high exposure. Numerical values were not necessarily assigned to each
category for each crop group. Selections depended upon the actual agronomic practices
that were identified for each group (i.e., some groups had 2 assigned transfer coefficients
while others had 5). The transfer coefficient values which have been used for pineapple
are excerpted directly from Agency Policy 003.1 for the vegetable, stem/stalk category.
The ARTF Scoping Survey does not specifically include pineapple; therefore, all
exposure levels (low, medium, and high) for the vegetable, stem/stalk category were
used. For lawn and turf activities, transfer coefficient values from Agricultural Reentry
Task Force (ARTF) study were used.
In addition to transfer coefficients, occupational postapplication exposures to
workers are estimated, in general, using transferable turf residue, dislodgeable foliar
residue or soil transferable residue values. Transferable turf residues (TTRs) are the
amounts of pesticide available on the turf surface that can potentially be transferred to the
skin of workers who contact treated turf. Dislodgeable foliar residues (DFRs) are the
amounts of pesticide available on the surface of crops (other than turf) that can
potentially be transferred to the skin of workers who contact treated crop. DFRs and
TTRs are measured using techniques that specifically determine the amount of residues
on the surface treated leaves or other plant surfaces. In order to define the amount of
transferable residues to which individuals can be exposed, whenever possible HED relies
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on chemical- and crop-specific studies as described in HED guidelines for exposure data
collection (Series 875, Occupational and Residential Exposure Test Guidelines: Group B
- Postapplication Exposure Monitoring Test Guidelines). However, when no chemical -
and crop-specific TTR or DFR studies are available, HED uses a standard modeling
approach to predict transferable residues over time (best described in HED's SOPsfor
Residential Exposure Assessment).
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7.2.2 Data/Assumptions for Postapplication Exposure Scenarios
A series of assumptions and exposure factors served as the basis for completing
the occupational postapplication worker risk assessments. Each assumption and factor is
detailed below on an individual basis. In addition to these values, transfer coefficient
values were used to calculate risk estimates. The transfer coefficients for pineapple were
taken from HED's revised policy entitled Policy 003.1 Science Advisory Council for
Exposure Policy Regarding Agricultural Transfer Coefficients (August 7, 2000). The
transfer coefficients for turf were taken a more recent study by the Agricultural Reentry
Task Force. The assumptions and factors used in the risk calculations are presented
below:
• There are many factors that are common to handler and postapplication risk
assessments such as body weights, duration, and application rates. See Section
2.1.1.1 for these values. In the postapplication risk assessment, maximum application
rates were considered.
• Levels of Concern: HED has established levels of concern (LOG) for occupational
postapplication risks - margins of exposure of less than 100 for occupational non-
cancer dermal and inhalation risks are a concern.
• Dislodgeable Foliar Residues: No chlorflurenol-specific dislodgeable foliar residue
(DFR) data were available for pineapple. Therefore, this assessment uses HED's
default assumption that 20 percent of the application rate is available on day 0 (i.e.,
12 hours after application) and the residue dissipates at a rate of 10 percent per day.
• Transferable Turf Residues: No chlorflurenol-specific transferable turf residue (TTR)
data were available. Therefore, this assessment uses HED's default assumption that 5
percent of the application rate is available on day 0 (i.e., 12 hours after application)
and the residue dissipates at a rate of 10 percent per day.
• Exposures were calculated to reflect default DFR and TTR values over time coupled
with surrogate transfer coefficients.
7.2.3 Occupational Postapplication Exposure and Non-cancer Risk
Estimates
Occupational non-cancer risks were calculated using a Margin of Exposure
(MOE), which is a ratio of the daily dose to the toxicological endpoint of concern.
Daily Exposure: Daily dermal exposures were calculated on each postapplication
day after application using the following equation (see equation D2-20 from Series 875-
Occupational and Residential Test Guidelines: Group B-Postapplication Exposure
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Monitoring Test Guidelines and Residential SOP 3.2: Postapplication Dermal Potential
Doses from Pesticide Residues on Gardens):
DE(t) (mg/day) = (TR(t) (jig/cm2) x TC (cm2/hr) x Hr/Day)/1000 (jig/nig)
Where:
DE(t) = Daily exposure or amount deposited on the surface of the skin at
time (t) attributable for activity in a previously treated area, also
referred to as potential dose (mg a.i./day);
TR(t) = Transferable residues that can either be dislodgeable foliar or turf
transferable residue at time "t" (jig/cm2);
TC = Transfer Coefficient (cm2/hour); and
Hr/day = Exposure duration meant to represent a typical workday (hours).
Note that the (TR(t)) input may represent levels on the day of application in the case of
short-term risk calculations.
Daily Dose and Margins of Exposure: The manner in which daily
postapplication dermal exposures were calculated is inherently different than with
handler exposures. However, once daily exposures are calculated, the calculation of
daily absorbed dose and the resulting Margin of Exposures use the same algorithms that
are described above for the handler exposures (See Section 2.1.3). These calculations are
completed for each day or appropriate block of time after application.
Non-cancer Risk Summary
For pineapple applications, the MOEs are greater than 100 on day 0 (REI =12 hours) for
all of the exposure levels.
For the golf course turf using the 1.0 and 1.1 Ib a.i./A (Label) rates for sprays and
granular applications respectively, the calculated MOE on day 0 (12 hours following
application) is 71 for liquid applications and 65 for granular applications (assuming 100%
dermal absorption) at the highest exposure level (hand weeding and transplanting). For
these postapplication scenarios, the target MOE is not reached until the 4l day after
application (MOE =110) for liquid formulations, and the target MOE is not reached until
the 5th day after application (MOE =110) for granular formulations. All other
postapplication turf scenarios using the 1.0 and 1.1 Ib a.i./A (Label) rates have risks
below FtED's level of concern on day 0 (12 hours following application).
For the golf course turf using the 3.0 Ib a.i./A (BEAD) rates for sprays and granular
applications, the calculated MOE on day 0 (12 hours following application):
• for liquid and granular applications (assuming 100% dermal absorption) is 24 at the
125
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higher exposure level (hand weeding and transplanting) and the target MOE is not
reached until day 14 (MOE=100);
• for liquid and granular applications (assuming 100% dermal absorption) is 47 at the
lower exposure level (mowing) and the target MOE is not reached until day 8
(MOE=110);
• for granular applications (assuming 10% dermal absorption) is 240 at the higher
exposure level (hand weeding and transplanting);
• for granular applications (assuming 10% dermal absorption) is 470 at the lower
exposure level (mowing).
Table 20 presents a summary of occupational postapplication risks associated
with use of chlorflurenol. The risk calculations for occupational chlorflurenol handlers
are included in Appendix C.
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Table 20. Summary of Occupational Postapplication Risks
Crop Grouping
Pineapple
Turf
Application
rate
(Ib a. i. /acre)
1.0 (Label &
BEAD)
1.0 -liquid
(Label)
3.0 -liquid
(BEAD)
1.1-
granular
(LABEL)
100%
dermal
absorption
1.1-
granular
(LABEL)
10% dermal
absorption
3.0-
granular
(BEAD)
100%
dermal
absorption
3.0-
granular
(BEAD)
10% dermal
absorption
Transfer Coefficient (|ig/cm2)
300 (irrigation, scouting, thinning,
hand weeding)
500 (irrigation, scouting)
1,000 (hand harvesting, hand
pruning)
3,400 (mowing)
6,800 (hand weeding, transplanting)
3,400 (mowing)
6,800 (hand weeding, transplanting)
3,400 (mowing)
6,800 (hand weeding, transplanting)
3,400 (mowing)
6,800 (hand weeding, transplanting)
3,400 (mowing)
6,800 (hand weeding, transplanting)
3,400 (mowing)
6,800 (hand weeding, transplanting)
Day after
Application
0 (12 hours)
0 (12 hours)
0 (12 hours)
0 (12 hours)
4
8
14
0 (12 hours)
5
0 (12 hours)
0 (12 hours)
8
14
0 (12 hours)
0 (12 hours)
MOE
(Level of
Concern = 100)
400
240
120
140
110
110
100
130
110
1,300
650
110
100
470
240
7.2.4 Occupational Postapplication Exposure and Risk Estimates for
Cancer
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Since no toxicological endpoint of concern was identified for cancer, cancer risks
from occupational postapplication exposures were not assessed.
7.2.5 Summary of Occupational Postapplication Risk Concerns and
Data Gaps
There are several occupational postapplication scenarios that have risks above
HED's level of concern for non-cancer risk assessments. For hand weeding and
transplanting of golf course turfgrass treated at 1.0/1.1 Ib a.i./A, the target MOE is not
reached until the 4th day after application (MOE =110) for liquid formulations, and the
target MOE is not reached until the 5th day after application (MOE =110) for granular
formulations. For the golf course turf using the 3.0 Ib a.i./A (BEAD) rates for sprays and
granular applications, the calculated MOE on day 0 (12 hours following application):
• for liquid and granular applications (assuming 100% dermal absorption) is 24 at the
higher exposure level (hand weeding and transplanting) and the target MOE is not
reached until day 14 (MOE=100);
• for liquid and granular applications (assuming 100% dermal absorption) is 47 at the
lower exposure level (mowing) and the target MOE is not reached until day 8
(MOE=110);
• for granular applications (assuming 10% dermal absorption) is 240 at the higher
exposure level (hand weeding and transplanting);
• for granular applications (assuming 10% dermal absorption) is 470 at the lower
exposure level (mowing).
FLED has used the most up-to-date information available to complete this
postapplication risk assessment for chlorflurenol. Several data gaps exist, such as a lack
of chlorflurenol-specific postapplication studies. Additionally, the ARTF Scoping Survey
does not include pineapple, though pineapple was assigned to the vegetable stem/stalk
transfer coefficient category in Policy 003.1.
7.2.6 Recommendations for Refining Occupational
Postapplication Risk Assessment
To refine this occupational risk assessment, data on actual use patterns including
rates, timing, and the kinds of tasks that are required to produce agricultural commodities
and other products would better characterize chlorflurenol risks. Exposure studies for
many cultural practices that lack data or that are not well represented in the revised
transfer coefficient policy should also be considered based on the data gaps identified
above.
8.0 Data Needs and Label Requirements
8.1 Toxicology
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Toxicology data requirements are acceptable and satisfied. However, another
study on reproduction with a more definitive NOAEL for effects on pups and fertility will
be necessary to remove the 3X uncertainty factor.
8.2 Residue Chemistry
A study on the UV/visible spectra is necessary.
8.3 Occupational and Residential Exposure
No studies are required at this time.
References:
Memorandum from Shana Recore to David G Anderson , dated June 30, 2006,
Subject: Chlorflurenol: Occupational and Residential Exposure Assessment for the
Reregi strati on Eligibility/Decision [RED].
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Appendix A: Toxicology Assessment
A.I Toxicology Data Requirements
A confirmatory study on reproduction [guideline 870.300] is necessary to remove
the extra 3X uncertainty factor and establish a NOAEL for pup effects and fertility effects
in adult offspring.
The requirements (40 CFR 158.340) for Non food use for CHLORFLURENOL METHYL ESTER are in
Table 1. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were
used.
Table A. 1: Data Requirements for a non-food use pesticide, such as chlorflurenol methyl ester.
Test
Technical
Required
Satisfied
870.1100 Acute Oral Toxicity
870.1200 Acute Dermal Toxicity
870.1300 Acute Inhalation Toxicity
870.2400 Primary Eye Irritation
870.2500 Primary Dermal Irritation
870.2600 Dermal Sensitization
870.3100 Oral Subchronic (rodent)
870.3150 Oral Subchronic (nonrodent)
870.3200 21-Day Dermal
870.3250 90-Day Dermal
870.3465 90-Day Inhalation
870.3700a Developmental Toxicity (rodent)
870.3700b Developmental Toxicity (nonrodent)
870.3800 Reproduction
870.4100a Chronic Toxicity (rodent)
870.4100b Chronic Toxicity (nonrodent)
870.4200a Oncogenicity (rat)
870.4200b Oncogenicity (mouse)
870.4300 Chronic/Oncogenicity
870.5100 Mutagenicity—Gene Mutation - bacterial
870.5300 Mutagenicity—Gene Mutation - mammalian
870.5300 Mutagenicity—Structural Chromosomal Aberrations.
870.5550 Mutagenicity—Other Genotoxic Effects
870.6100a Acute Delayed Neurotox. (hen) E
870.6100b 90-Day Neurotoxicity (hen) E
870.6200a Acute Neurotox. Screening Battery (rat)F
870.6200b 90-Day Neuro. Screening Battery (rat)F
870.6300 Develop. Neuro F
870.7485 General Metabolism
870.7600 Dermal Penetration
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
no
no
no
no
yes
no
no
no
no
A
yes
no
no
Yes
n°B
noB
no
no
no
no
no
No
yes
no
yes
no
c
D
yes
yes
yes
yes
yes
yes
yes
yes
no
no
no
no
no
no
no
no
no
130
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Test
Special Studies for Ocular Effects H
Acute Oral (rat)
Subchronic Oral (rat)
Six-month Oral (dog)
See next page for explanation for superscripts A to H.
Technical
Required
Satisfied
Footnotes for Table A. 1: A A formulation rather than the technical grade of chlorflurenol was studied
[technical grade is required]. B The unacceptable developmental rabbit study and unacceptable
reproduction studies submitted were not required. c The acceptable chronic dog study submitted was not
required. D The acceptable carcinogenicity study in the mouse was not required. E Required only for
organophosphate pesticides. F Required if the pesticide shows evidence of neurotoxicity. G Not required
for pesticides with this use pattern.
A.2 Toxicity Profiles
Table A.2.1 Acute Toxicity Profile - Chlorflurenol methyl ester
Guideline No.
870.1100
870.1200
870.1300
870.2400
870.2500
870.2600
Study Type
Acute oral [rat]
Acute dermal [rabbit]
Acute inhalation [rat]
Acute eye irritation [rabbit]
Acute dermal irritation [rabbit]
Skin sensitization [Guinea pig]
MRID(s)
43355402
43355403
45147201
43355404
43355405
43361701
Results
LD50 > 5000
mg/kg
LD50 > 5000
mg/kg
LC50 > 5.07 mg
a.i./L
Mild irritation,
cleared in 72
hours
Practically non
irritating
Not a sensitizer
Toxicity Category
IV
IV
IV
III
IV
Negative
Table A.2.2: Subchronic, Chronic, Developmental, Reproduction , mutagenicity and other toxicity
profile of chlorflurenol methyl ester.
Guideline/
Study type/
Acceptability
870.3100
90-Day oral/SD
rat
Acceptable
Lot# 45, 99.9%
MRID#/Date/
Doses
45441001 [2001]
Acceptable
0,1000,5000,10000
ppm [M: 0,74,361,
697; F:
0,87,390,750
mg/kg/day]
Results
NOAEL = M/F 697/87 mg/kg/day
LOAEL = M/F None/390 mg/kg/day based decreased body weight
gain in females [Female B Wt accompanied by decreased food
efficiency]. Males showed a possible treatment related nominal
decreased body weight gain of 1 1% at 697 mg/kg/day.
131
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Table A.2.2: Subchronic, Chronic, Developmental, Reproduction , mutagenicity and other toxicity
profile of chlorflurenol methyl ester.
Guideline/
Study type/
Acceptability
MRID#/Date/
Doses
Results
870.3100
90-Day
oral/Wistar rat
Unacceptable
00120854 &
00120867 [1968] 0,
1000, 5000, 10000
ppm [0, 50, 250,
500 mg/kg/day]
NOAEL = 250 mg/kg/day
LOAEL = 500 mg/kg/day based on body weight decrement in
females.
Unacceptable: lacking hematology clinical chemistry & some
histology
870.3150
90-Day oral/dog
Unacceptable
00120868 [1968]
Unacceptable
0,300,1000,3000
ppm
0, 8.95, 29.9, 89.5
mg/kg/day
NOAEL = >89.5 mg/kg/day
LOAEL = None. No treatment related decreases in hematological
parameters, which showed only random fluctuation from control
animals and from pre-dosing conditions in males and female up to 8
weeks. Although, some parameters at the HOT were slightly
numerically less than control values, they were not consistently less
or consistently numerically less than the initial values for the group.
The 90-day dog was not entirely inconsistent with the 2-year dog
study.
Unacceptable; only 3 dogs/sex/group and dose levels were not
verified.
870.3150NG
21-Day dermal
toxicity/
rabbit, Proj# 1385
Lot# 759-78
Acceptable/NG
00120883 [1970]
Acceptable/NG
Test material CF-
125 [12.5% a.i.]
Doses 0, 0.5, 1.0
ml/kg/day or .0,
62.5, 125 mg a.i./kg
NOAEL = None
LOAEL = 62.5 mg a.i./kg/day based on dose related local
degeneration of hair follicles and epithelial thickening at the 2 dose
levels used. No systemic effects reported. Since the test material
was applied as a neat formulation, the dermal effects may have been
due to the dispersing agent in CF-125. CF-125 is 12.5% active
ingredient with 87.5% being inert ingredients of which most were
known skin irritants in the context of this study.
Acceptable as a non-guideline study. The toxicity of the technical
grade of the pesticide could not be evaluated.
870.4 lOOb
Chronic toxicity
Dog
Acceptable
00082863 [1975]
0, 300, 1000, 3000
ppmor[M/F:0/0,
8.7/8.8, 30.6/29.9,
94.0/94.4
mg/kg/day
NOAEL = 30.6/29.9 mg/kg/day for males/females. LOAEL =
94.0/94.4 mg/kg/day for male/females based on decreased
erythrocytes, hemoglobin and hematocrit by week 4 in males and
females, supported by hemosiderin deposits in liver and incidence of
gastritis and possible decreased body weight in males and females
by month 13 of the study, but not in females by study termination at
24 months. Transient alkaline phos. and elevated SGPT was seen at
the HOT.
870.4100a
Chronic toxicity
rats
Unacceptable
00082864 [1971]
0, 300, 1000, 3000
ppm or 0, 15,50,
150 mg/kg/day
52 week interim report.
Tentative NOAEL = 50 mg/kg/day
LOAEL =150 mg/kg/day based on one male with
elevated SGPT and alkaline phos.
Unacceptable: Inadequate number of rats were studied histologically
132
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Table A.2.2: Subchronic, Chronic, Developmental, Reproduction , mutagenicity and other toxicity
profile of chlorflurenol methyl ester.
Guideline/
Study type/
Acceptability
MRID#/Date/
Doses
Results
for too short a period.
870.4200b
Carcinogenicity
Mouse
Acceptable
00082865 [1976]
0, 1000, 3000,
10000 ppm or 0,
150, 450, 1500
mg/kg/day
NOAEL = 1500 mg/kg/day
LOAEL = None, no dose related carcinogenic response was noted.
Acceptable
Non GDL
Carcinogenicity
Rats
Unacceptable
0082866 [1969]
subcutaneous 0, 30
mg/kg/week, and
feeding about 92
mg/kg/day or about
700 mg/kg/week.
Subcutaneous dose:
NOAEL = 30 mg/kg/week
LOAEL= None
Feeding study:
NOAEL = 92 mg/kg/day
LOAEL= None
Unacceptable because studied for 1-year only
870.3700a
Developmental
toxicity/ SD rat
Acceptable
4510901 [2000]
Acceptable
0, 250, 750, 1000
mg/g/day
Maternal: NOAEL = 250 mg/kg/day
LOAEL = 750 mg/kg/day based on statistically
significant and treatment related reduced body weight gain during
the treatment period, GD 6-16.
Devel: NOAEL = 250 mg/kg/day
LOAEL = 750 mg/kg/day based on treatment related
increased incompletely ossified anterior skull bones [nasal and
frontal bones about doubled that of controls]. In addition a cleft
palate was seen in each of two litters and one diaphragmatic hernia
at 1000 mg/kg/day and one cleft palate at 750 mg/kg/day [cleft
palate is rare in rats, historical incidence not given].
870.3700b
Developmental
toxicity/NZW
rabbit
Unacceptable
00120862 [1969]
Unacceptable
Proj# 1624-97
0, 25, 50, 100
mg/kg/day
Maternal NOAEL = 100 mg/kg/day
LOAEL = None
Devel NOAEL = 100 mg/kg/day
LOAEL = None, although a wide variation in skeletal
variants were seen among the groups.
Unacceptable due to no demonstrated toxicity and lack of individual
animal data and no indication that fetal soft tissue was evaluated.
870.3800
3-Generation
reproduction/Char
les River rat
Unacceptable
00082867 [1973]
0, 300, 1000, 3000
ppm or 0, 15,50,
150 mg/kg/day
Parental, systemic NOAEL = 50 mg/kg/day.
Systemic LOAEL =150 mg/kg/day for nominal decreased
body weight.
Offspring NOAEL = 15 or 50 mg/kg/day
LOAEL = 50 or!50 mg/kg/day based on decreased pup
weight at birth and/or litter size from the POb, Fla and Fib
generations. Decreased absolute thymus and testes weights in the
F3b generation weanling pups [The only group from which organ
weight were collected].
Reproduction NOAEL = Unknown.
LOAEL = Unknown. Appears to be considerable
variation in results generation to generation such that
133
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Table A.2.2: Subchronic, Chronic, Developmental, Reproduction , mutagenicity and other toxicity
profile of chlorflurenol methyl ester.
Guideline/
Study type/
Acceptability
MRID#/Date/
Doses
Results
NOAEL/LOAEL was not definitive. Reviewer could not assign a
NOAEL. Decreased variable pregnancy rate in the Fla, Fib, F2a
and F2b generation [only F2a shows a dose relationship], decreased
absolute thymus in F3b weanlings [The only group from which
organ weight were collected]. Female FO and F2 body weight gain
was lower than controls premating in the 150 mg/kg/day group.
Unacceptable due to uncertainty and variability in pregnancy rates in
control and all doses.
870.5100
Ames, S
typhimurium
43562802 [1995]
Acceptable
In a reverse mutation assay with S tryphimurim [TA1535, TA 1537,
TA1538, TA98 and TA100] was exposed with and without S9
activation at 250, 500, 750, 1000 or 2500 ug/plate. Cytotoxicity
was seen in all strains at 2500 ug/plate.
There were no signs of a mutagenic response with or without S9.
870.5300
In vitro cell
(CHO)
Chromosomal
Aberration
43562801 [1995]
Acceptable
In this Chinese hamster ovary cell in vitro assay, cells were exposed
to non-activated doses of 5.0-75 ug/mL and activated doses of 50-
200 ug/mL. Treated cultures were scored for structural aberrations.
Cytotoxicity was indicated by approximately 40% reduction in
mitotic index at the highest dose in the non-activated and activated
systems.
There was no indication of clastogenic effects in the non-activated
or activated systems.
870.5550
In vitro rat
hepatocyte UDS
45137404 [1988]
Acceptable
Chlorflurenol was studied for unscheduled DNA synthesis in rat
hepatocytes at 0, 1.5, 5, 15, 50 or 150 ug/mL. Cytotoxicity was seen
at 150 ug ML indicated by decrease [3H] thymidine incorporation.
Since there was no evidence UDS with or without S9 activation, the
study was considered negative for mutagenic evidence.
870.5300
In vitro
mammalian cell
HGPRT test
45137405 [1988]
Acceptable
In two independently performed mammalian cell gene mutation
assays at the HPRT locus (MRID 45137405), V79 cells cultured in
vitro were exposed to Chlorflurenol-methyl ester in ethanol at 0, 6,
20, 40, or 60 ug/mL with and without S9 to the solubility limit.
There was no evidence that Chlorflurenol-methyl ester induced
mutant colonies over background in the presence or absence of S9-
activation.
NG
Metabolism &
Pharmacokinetics
Unacceptable/NG
00082868 [1972]
Unacceptable/NG
Majority eliminated via the rat kidney and about 1/20 in the feces.
The small amounts detected in the mammary gland suggested that
the test material was not secreted in milk. Recovered test material
from the feces and urine within 72 hours after administration were
64% IT-3456, 75% of IT-5733 and 83% of IT-3294. Biliary
recyclization was indicated. Small amounts were detected in the
mammary gland of lactating females, but not in their pups.
134
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Table A.2.2: Subchronic, Chronic, Developmental, Reproduction , mutagenicity and other toxicity
profile of chlorflurenol methyl ester.
Guideline/
Study type/
Acceptability
MRID#/Date/
Doses
Results
Identification of potential metabolites was not investigated.
Unacceptable due to inadequate replication, distribution not
quantitated, test material inadequately identified.
A.3 Executive Summaries
Summaries included are acceptable and unacceptable studies considered, but
not necessarily used to assess risk.
A.3.1 Subchronic Toxicity
870.3100 90-Day Oral Toxicity - Rat [MRID# 45441001]
EXECUTIVE SUMMARY: In a 90-day dietary study (MRID 45441001), chlorflurenol
methyl ester (Lot# 45, 99.9% pure) was administered to 10 Sprague Dawley
rats/sex/group at dietary levels of 0, 1000, 5000 or 10000 ppm (males: 0.0, 74, 361 or 697
mg/kg/day; females: 0.0, 87, 390 or 750 mg/kg/day). Body weights, food consumption,
and clinical observations were recorded. Ophthalmoscopic examinations were
conducted. At study termination, rats were sacrificed and blood collected for hematology
and clinical chemistry studies. Organ weights were recorded and gross and microscopic
examinations were conducted.
All rats survived to terminal sacrifice. There were no clinical signs of toxicity
and there were treatment related effects on hematology or clinical chemistry parameters,
organ weights or necropsy findings. All treated groups of female rats had dose-related
lower final body weight than control group (not significant) and dose-related lower body
weight gains (reduced in Groups 2, 3 and 4 by 15, 21 and 24%, respectively) which were
statistically significant in the 5000 ppm and 10000 ppm groups (p<0.01). The food
consumption and food efficiency were also lower in all treated groups compared with the
control group.
Under the conditions of this study, a NOAEL for females was established at
1000 ppm (87 mg/kg/day) and a LOAEL at 5000 ppm (390 mg/kg/day) based on dose-
related decrease in body weight gain. For males the NOAEL was 10000 ppm 697
mg/kg/day and a LOAEL was not established.
This study is considered to be ACCEPTABLE/GUIDELINE as a 90-day
study and fulfills FIRA Guideline requirements for a Subchronic oral toxicity study in the
rat [870.3100 (82-la)].
COMPLIANCE: Signed and dated GLP, Quality Assurance and Data confidentiality
statements were provided.
135
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870.3100 90-Day Oral Toxicity - Mouse
Not required and none was submitted.
870.3150 90-Day Oral Toxicity - Dog [MRID# 00120868]
Not required and unacceptable because only 3 dogs/sex/group were used and no
toxicity was demonstrated
870.3200 21/28-Day Dermal Toxicity - Rat [MRID# 00120883]
EXECUTIVE SUMMARY: In a 21-day dermal toxicity study (MRID 00120883),
formulated chlorflurenol methyl ester [Lot# 759-78 (12.5% a.L, batch/lot # 759-78)] was
applied to the shaved skin of 5 New Zealand rabbits/sex/group at dose levels of 0, 0.5 or
1.0 ml/kg bw/day [equivalent to 0, .62.5 mg a.i./kg/day or .125 mg a.i./kg/day, assuming
a density of 1.0 g/ml for CF 125] 24 hours/day for 5 days/week during a 21-day period.
Equal numbers of rabbits and dose levels were evaluated with abraded and intact skin.
The only treatment related effects seen were in the treated skin. Drying and slight
fissuring of the skin midway through the study was noted, which at termination resulted
in epithelial thickening and varying amounts of keratonization with varying destruction
of hair follicles. Although the varying degrees of destruction of hair follicles was shown
in most dosed animals, the damage was observed to be less severe among the lowest
dosed animals. The treated skin effects were believed to be due to the 87.5% of the CF
125 formulation that were skin reactive inerts. Only mild skin effects were noted at mid
study.
No treatment related changes were noted in body weight, weight gain,
hematology, clinical chemistry, organ weights, or systemic toxicity in treated animals.
Histological findings were consistent with random effects in controls and treated animals.
There were no systemic effects. The LOAEL is 62.5 mg/kg/day, based on
epithelial thickening, keratinization and destruction of hair follicles. A NOAEL was
not seen for skin effects.
This 21-day dermal toxicity study in the (rabbit) is an ACCEPTABLE/NON-
GUIDELINE study and does not satisfy the guideline requirement for a 21/28-day
dermal toxicity study (OPPTS 870.3200 ; OECD 410) in the rabbit. The technical grade
of the test material was not studied. It is not upgradeable because some of the
recommended parameters were not studied, including some hematology, clinical
chemistry and histopathology parameters, but the major parameters were studied. The
study is useful in that it shows no systemic toxicity at 125 mg/kg/day with a reasonable
degree of certainty.
136
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COMPLIANCE: Signed and dated GLP, Quality Assurance, and Data Confidentiality
statements were (not) provided. The study was conducted prior to publication of these
regulatory requirements.
870.3465 90-Day Inhalation - Rat
A.3.2 Prenatal Developmental Toxicity
870.3700a Prenatal Developmental Toxicity Study - Rat
EXECUTIVE SUMMARY: In a developmental toxicity study (MRID 45190901) with
chlorflurenol-methyl ester [calculated as 99.1% a.L; batch/lot# UT 047843] was
administered to 31 female, Crl:CD(SD):BR strain of Sprague Dawley rats/group by
gavage at dose levels of 0, 250, 750 or 1000 mg a.i./kg bw/day from days 6 through 15 of
gestation. Doses were administered in 1% carboxymethyl cellulose/water in a volume of
5 mL/kg/day. Maternal toxicity was evaluated and fetal evaluations were conducted one-
half the fetuses viscerally or skeletally.
Maternal toxicity was seen as a statistically significant decrement in body
weight gain gestational days 6 to 16 at 750 and 1000 mg/kg/day and at 1000 mg/kg/day
gestational day 6-9. Supporting this body weight decrement was nominally decreased
food efficiency at 750 and 1000 mg/kg/day.
The maternal NOAEL was 250 mg/kg/day. The maternal LOAEL is 750 mg/kg
bw/day based on body weight gain decrement and nominally decreased food
efficiency. Delayed ossification was seen in skull bones. The incidence of incompletely
ossified nasal bones and frontal bone were increased at 750 and 1000 mg/kg/day (60.9-
63.0% vs. 28.6% in control] and 55.6%-60.9% vs. 33.3% in control], respectively.
Intrauterine death was borderline statistically significant [p = 0.0529] at 1000 mg/kg/day
[1.7 vs. 0.3 in control]. The post-implantation loss and early resorptions, which were
nominally increased at 1000 mg/kg/day supported the intrauterine death at 1000
mg/kg/day.
The developmental NOAEL is 250 mg/kg/day. The developmental LOAEL is 750
mg/kg bw/day, based on treatment related delayed ossification in skull bones [nasal
and frontal] in fetuses and litters.
The developmental toxicity study in the rat is classified ACCEPTABLE [guideline];
and satisfies the guideline requirement for a developmental toxicity study (OPPTS
870.3700; OECD 414) in the rat.
COMPLIANCE: Signed and dated GLP, Quality Assurance, and Data Confidentiality
statements were provided. Historical control data was submitted for fetuses, but not for
litters.
870.3700b Prenatal Developmental Toxicity Study - Rabbit
137
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Study not required and unacceptable [MRID# 00120862] due to failure to
submit data on fetal soft tissue and study showed no toxicity in dams or fetuses.
EXECUTIVE SUMMARY: In a developmental toxicity Study (MRID#s 00120862,
00069980 and 00073536), IT 3456 (chlorflurenol methyl ester, 98% a.i.) was
administered by gastric intubation to 13-14 New Zealand female rabbits/group at dose
levels of 0, 25, 50 or 100 mg/kg/day from days 6 through 18 of gestation. The submitted
study consists of a summary of the data that was previously submitted to the Agency
prior to implementation of GLP standards as well as copies of the original MRIDs.
There were no treatment related effects in mortality, clinical signs of toxicity, body
weight, or cesarean parameters. Equivocal reductions in body weight gain were noted at
the mid dose (50 mg/kg/day). A maternal LOAEL was not observed. The maternal
NOAEL under the conditions of the study is => 100 mg/kg/day.
There were no treatment related effects in developmental parameters including mortality,
body weight, abnormalities or skeletal parameters. A developmental LOAEL was not
observed. The developmental NOAEL under the conditions of the study is => 100
mg/kg/day.
The study is classified UNACCEPTABLE/GUIDELINE (870.3500 OR 83-3b) and
does not satisfy the guideline requirements for a developmental study in rabbits and a
new study must be conducted. No maternal or developmental toxicity was observed. It
appears that the animals could have tolerated a higher dose level, however, the dose
rationale was not provided. In addition the following acceptance criteria were not met:
individual fetal soft tissue and skeletal examinations were not performed; at least 12
pregnant animals/dose group were not available because 3 pregnant rabbits died during
the study; and food consumption was not reported. Moreover, this study should have
been properly reformatted as per EPA requirements. It therefore seems unlikely this
study can be upgraded. .
A.3.3 Reproductive Toxicity
Not required for a non-food use pesticide, but may show subfertility in
offspring.
870.3800 Reproduction and Fertility Effects - Rat [MRID# 0008267]
EXECUTIVE SUMMARY: In a three-generation study on reproduction [MRID#
00082867], Charles River rats [20 females/group and 10 males/group] were administered
chlorflurenol methyl ester at 0, 300, 1000 or 3000 ppm [Standard table equivalent for PO
males and females: 0, 15, 50 or 150 mg a.i./kg/day] in the diet continuously for 3
generations. Twenty-one-day old pups [10/sex/group] from only the 3rd generation were
subjected to necropsy; organs were weighted and microscopically examined.
Female body weight was consistently lower in the 1000 and 3000 ppm group than
in controls in all generations, PO [96% and 89% of control, respectively], Fl [93% and
138
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87% of control, respectively] and F2 [93% and 91% of control, respectively]; none of the
reductions in weight were statistically significant. Male body weight was unchanged.
Pup weight was statistically significantly decreased at 1000 and 3000 ppm in the
PO, first litter [91% and 89% of control, respectively] at day 4, but not at birth and only
at 3000 ppm in the second litter at birth (96% of contraband day 4 (91% of control).
Again for the F2 generation at 1000 and 3000 ppm, the first litter weight was statistically
significantly reduced [91% and 92% of control, respectively] at day 4, but not at birth of
for the second litter at either dose. Litter size appeared to be sporadically decreased at
3000 ppm in the PO second litter at birth and at day 4, and the Fl for both litters, but not
for the F2 for both litters.
Litter size at birth was statistically significantly reduced at 3000 ppm in 3 of the 6
sets of litters produced during the study [PO second litter, F1 first and second litter, but
not in the F2 first or second litter].
Body weight of the F3, 21-day old pups was significantly reduced at 3000 ppm.
Absolute and relative brain weight was statistically significantly reduced [90% of
control]. Absolute gonad weight was reduced at 1000 and 3000 ppm [85.1% and 84.6%
of control, respectively], but the relative weight did not differ from control. Microscopic
examination showed no histopathology. The only comment about the gonads was that all
animals showed immaturity as may be expected from 21-day old gonads.
There was a problematic apparent decrease in fertility at all dose levels in this
1973 study, which showed a statistically significant dose relationship only in the first
mating of the F2 generation at 1000 [50%] and 3000 ppm [40%] compared with control
at 90% and the 300 ppm group at 80%. The other matings showed lower fertility than
control, but little to no dose response was shown [See accompanying table in the
Appendix]. The PO first and second matings showed no dose related effects on fertility,
while the Fl first and second matings were lower than control and for the F2 second
matings, control and high dose groups were equally low. The suggestion of subfertility in
these rats may have been shown, but unproven. Another study on reproduction is needed
to confirm or reject the potential effects on fertility and pups.
Out of 479 matings, 145 showed sperm negative vaginal smears of which 29 of
these females produced litters. This appears to be a high number of pregnancies for
which no vaginal sperm were shown. When all pregnant females showing no sperm
during cohabitation were added together for the 6 total matings, a treatment related
increased response was seen in the data [last four rows of the table of matings,
pregnancies, and pregnancies with out demonstrated sperm during cohabitation in the
Appendix]. (The method used in determining the presence of vaginal sperm was not
stated and may have been inadequate or the sperm count for some rats was extremely
low.} In addition, if estrous cycles were noted they were not recorded. Only the time to
pregnancy was recorded. Historical control levels were not presented for vaginal sperm
negative females producing litters. It is the experience of this reviewer that out of 145
sperm negative vaginal spears, no more than 2-3 of these rats would produce pregnancies
and none would be expected to produce pregnancies.
The study raises unanswered questions about possible effects of chlorflurenol on
fertility in rats. Histopathology on 21 day old F3 pups showed no histological effects on
139
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testes or ovaries [the only pups studied for these effects]. No gonadal effects were noted
in the 2-year chronic dog study or the 90-day study in rats. The study on reproduction
should be repeated to clarify the questionable results in MRID# 00082867.
Neither the NOAEL nor the LOAEL can be determined due to the variability
from generation to generation. However, litter size at birth and pup weight decrement
were statistically significantly reduced at the HDT of 3000 ppm..
The study is UNACCEPTABLE/GUIDELINE and is not satisfactory for a study
on reproduction in rats [870.3800] . The data in the study was too variable for adequate
interpretation.
Table of Response of litters in the 3 -generation study on reproduction [MRID# 00082867]
Generation Parameter Control 15 mg/kg/day 50 mg/kg/day 150 mg/kg/day
PO 1st mating
PO 2nd mating
Fl 1st mating
Fl 2nd mating
F2 1st mating
Pup wt at birth
At day 4
At day 12
Atday21
Litter size at birth
At day 4
At day 12
At day 21
Pup wt at birth
At day 4
At day 12
Atday21
Litter size at birth
At day 4
At day 12
At day 21
Pup wt at birth
At day 4
At day 12
Atday21
Litter size at birth
At day 4
At day 12
At day 21
Pup wt at birth
At day 4
At day 12
Atday21
Litter size at birth
At day 4
At day 12
At day 21
Pup wt at birth
At day 4
At day 12
Atday21
Litter size at birth
At day 4
6.3
11.1
29.0
58.2
12.0
12.1
12.0
12.0
6.5
11.6
31.2
58.7
12.4
12.0
11.9
11.9
6.2
10.2
27.1
54.7
13.1
12.2
11.9
11.8
6.7
11.4
28.9
55.0
12.9
12.3
12.1
11.9
6.2
10.5
27.7
53.4
12.3
11.6
6.1
10.4
27.1
50.8
12.2
11.2
11.2
11.2
6.6
11.7
30.5
55.5
11.8
10.9
10.9
10.9
6.7
10.8
28.2
53.2
11.3
9.9
9.7
9.7
6.6
10.9
26.2
48.5
12.5
12.2
11.9
11.8
6.3
10.5
26.9
51.5
12.9
12.1
6.0
10.1*
25.3**
49.9*
13.1
12.1
11.8
11.8
6.4
11.0
29.9
55.4
11.91
11.2
11.1
11.1
6.6*
9.4
23.7
47 i**
11.2
10.4
10.0
10.0
6.8
11.1
26.0
50.6
11.6
12.0
10.7
11.9
6.2
9.6*
24.8*
48.4*
12.8
12.2
6.0
9.9*
24.9**
47.2**
12.0
11.4
11.4
11.4
6.2*
10.6*
28.5**
52.8
10.7*
9 g**
9 g**
9 7**
6.6
10.1
26.9
50.8
8.8**
g 1***
7 9***
7 9***
6.7
11.0
26.8
49.8
9.8*
9 3**
9 2**
9.2*
6.1
9.7*
25.6
49.7
10.5
10.0
140
-------
Table of Response of litters in the 3-generation study on reproduction [MRID# 00082867]
Generation Parameter Control 15 mg/kg/day 50 mg/kg/day 150 mg/kg/day
F2 2nd mating
1 1
At day 12
At day 21
Pup wt at birth
At day 4
At day 12
Atday21
Litter size at birth
At day 4
At day 12
At day 21
p<0.05.<0.01 orO
11.4
11.4
6.2
10.4
26.0
51.0
12.1
11.0
10.7
10.5
001
11.9
11.9
6.6
10.7
26.2
51.9
13.8
13.0*
12.7
12.2
12.0
12.0
6.4
10.3
24.6
50.4
12.2
11.5
11.3
11.2
9.8
9.6
6.0
10.3
23.9
46.1
11.4
11.0
11.0
11.0
Table of matings, pregnancies and pregnancies without apparent sperm for PO, Fl and F2 generations [MRID# 00082867]
Data taken from page 42-46.
Dose group
[mg/kg/day]
Total mating
with positive
sperm smears a
Total
pregnancies
[with positive &
negative sperm]
Not pregnant
[with positive
& negative
sperm]
# rats without sperm positive
smears
Total
Pregnant
Not
pregnant
Pregnancy
rate [%]
1st PO Mating with 20 females/group
0
300
1000
3000
19
14
19
16
20
13
18
18
0
7
2
2
1
6
1
4
1
2
1
2
0
4
0
2
100
65**
90
90
2nd PO mating with 20 females/group
0
300
1000
3000
18
14
20
18
18
15
20
20
2
5
0
0
2
6
0
2
0
2
0
2
2
4
0
0
90
75*
100
100
1st Fl mating with 20 females/group
0
300
1000
3000
13
14
11
9
14
11
12
11
6
9
8
9
7
6
9
11
2
2
1
4
5
4
8
7
70
55
60
55
2nd Fl mating with females/group
0
300
1000
3000
16
12
11
10
14
11
10
12
6
9
10
8
4
8
9
10
0
1
2
2
4
7
7
8
70
55
50
60
1st F2 mating with 20 females/group
0
300
1000
3000
19
15
9
7
18
16
10
8
2
4
10
12
1
5
11
13
0
1
1
2
1
4
10
11
90
80
50*
40**
2nd F2 mating with 19 females in control and 20 females/.dose group
0
300
1000
3000
12/19
12
7
9
12/19
11
6
7
7/19
9
14
13
7/19
8
13
11
0/19
1
0
0
7/19
7
13
11
63
55
30
35
141
-------
Table of matings, pregnancies and pregnancies without apparent sperm for PO, Fl and F2 generations [MRID# 00082867]
Data taken from page 42-46.
Dose group
[mg/kg/day]
Total mating
with positive
sperm smears a
Total
pregnancies
[with positive &
negative sperm]
Not pregnant
[with positive
& negative
sperm]
# rats without sperm positive
smears
Total
Pregnant
Not
pregnant
Pregnancy
rate [%]
Summary results of total PO, Fl and F2 matings, including controls
Total
324/479
325/479
154/479
155/479
29/479
126/479
68
Summary data from the first and second matings of the PO, Fl and F2 generations
0
300
1000
3000
97/119
81/120
77/120
69/120
97/119
77/120
76/120
76/120
21/119
43/120
44/120
44/120
22/119
39/120
43/120
51/120
3/119
9/120
5/120
12/120
19/119
30/120
38/120
39/120
80.7
64.2
63.3
63.3
a = # females mated with positive sperm smears. * = p > 0.05, ** = p > 0.01.
A.3.4 Chronic Toxicity
870.4100a (870.4300) Chronic Toxicity - Rat [MRID# 00082864]
Unacceptable as a chronic study due to several factors, especially microscopic
examination was conducted on only 3 rats/sex
870.4100b Chronic Toxicity - Dog {MRID# 00082863]
EXECUTIVE SUMMARY: In a chronic toxicity study (MRID 00082863) IT 3456
[Chlorflurenol, technical (96% a.i., batch/lot # 5/69)] was administered to 4 Beagle
dogs/sex/group in the diet at dose levels of 0, 300, 1000 or 3000 ppm (for male/female
equivalent to 0, 8.7/8.8, 30.6/29.9 or 94.0/94.4 mg/kg bw/day, calculated from test
material consumption) for 104 weeks. One extra dog/sex/group was treated with test
material for 104 weeks, after which the dogs were untreated for 8 weeks. Hematology
and clinical chemistry evaluation was performed at 6 intervals during the study. Animals
were subjected to gross pathology and microscopic examination.
Body weight appeared to be slightly reduced by month 13 at the highest dose
tested [HDT]. Dogs showed this body weight decrement at month 13 when compared
with initial body weights for males [the HDT gained 0% vs. 22.3% for control weight]
and for females [the HDT gained 6.6% vs. 20.3% for control body weight]. Male body
weight gain appeared to be reduced for the remainder of the study. Male body weight
gain was decreased at 104 weeks [body weight gain was 0.8 kg at the HDT and 2.5 kg for
controls]. At the end of the study female body weight gain was the same as control
weight gain. Food consumption was unaffected in both sexes.
Erythrocytes [ERY], hemoglobin concentration [Hb] and hematocrit [Ht] values
appeared to be slightly decreased at the HDT in males and females starting at week 4 [the
first time period evaluated] and male dogs maintained a decrease through out the study.
Some of the values in the HDT were statistically significantly reduced, but were still
within the normal range for dogs. The DERY, DHb and DHt values [difference between
measured values and week -2 values] appeared to decrease in males and females at the
142
-------
HDT starting at week 4 and male dogs maintained the decrease through out the study.
This decrease is consistent with the slightly higher incidence and/or severity of siderous
in the spleen, liver and Kupffer cells at the HDT. Hemosiderin in the 1000 ppm group
was not considered sufficiently consistent to show that the mid dose group was affected.
In addition the values for ERY, Hb and Ht from the 1000 ppm group of animals did not
show consistent effects. From week 26-52 to termination, the values for ERY, Hb and Ht
for treated female dogs did not appear to differ from control.
Clinical chemistry values showed no consistent treatment related effects. Organ
weights were unchanged from control values.
On microscopic examination increased hemosiderin in liver and liver Kupffer
cells and possibly in the spleen at the HDT seemed to confirm the hematological effects.
In addition, the highest dose group showed higher incidence of gastritis and possible
stomach lymphatic hyperplasia.
A single dog/sex was allowed to recover for 2 months and although the
hemosiderin appeared to decrease, effects in one dog are difficult to interpret.
The NOAEL was 30.6/29.9 mg/kg/day for males/females. The LOAEL was
94.0/94.4 mg/kg/day for male/females based on decreased erythrocytes, hemoglobin
and hematocrit by week 4 in males and females, supported by hemosiderin deposits
in liver and increased incidence of gastritis and possible decreased body weight in
males and females by month 13 of the study, but not in females by study termination
at 24 months.
This study is ACCEPTABLE/GUIDELINE and satisfies the guideline
requirement [870.4100b] for a dog chronic study. This DER takes precedence over
previous conclusions.
A.3.5 Carcinogenicity
870.4200a Carcinogenicity Study - rat [MRID# 00082866]
Unacceptable due to only 1-year interim report of a 2-year study was submitted.
and other factors Not required.
870.4200b Carcinogenicity (feeding) - Mouse [MRID# 00082865]
SUMMARY: In a Carcinogenicity study in mice [MRID 00082865], 50 NMBI-FMD-
SPF mice/sex were administered IT 3456 [chlorflurenol methyl ester] in the feed at 0,
1000, 3000 orlOOOO ppm [equivalent to Males: 0, 136, 397 or 1538 mg/kg/day; Females:
0,158, 504 or 1905 mg/kg/day] for 18 months. Weekly body weights were determined up
to week 12 and every two weeks to termination. Weekly food consumption was
determined up to week 12 and every two weeks to termination. Necropsy and
microscopic examination of the tissue were performed at termination.
143
-------
No dose related or treatment related effects were noted in any parameter studied.
Mortality, body weight, and food consumption were unchanged. Random tumors were
seen after microscopic examination, but a dose or treatment relationship was absent.
Neoplasms of the reticular tissue were 8.25%, 15.96, 15.63 and 14.13%, respectively in
control, 1000 ppm, 3000 ppm and 10000 ppm. Since historical control data for this
neoplasm ranges from 5% to 28%, control appear to be low compared with dosed groups.
In addition, although over a 10 fold dose range, no dose response was seen. The highest
incidence of tumors were pulmonary adenomas. Total pulmonary adenomas [benign and
malignant] were 15.5%, 9.6%, 12.5% and 9.8%, respectively in control, 1000 ppm, 3000
ppm and 10000 ppm.
No dose related toxic or carcinogenic effects were noted in mice above the limit
dose level of 1 g/kg/day.
The NOAEL was the highest dose tested of 1538/1905 mg/kg/day in male and
female mice. A LOAEL was not seen.
The study is ACCEPTABLE/GUIDELINE and satisfies the requirements for a
carcinogenicity study in mice [870.4200]. The study was done prior to GLPs. Organ
weights were not determined and some summary table were not presented, but the study
results appeared to be adequate to show that there were no carcinogenic response in mice
to chlorflurenol administration.
A.3.6 Mutagenicity
See Table A.2.2 for summary of the mutagenicity studies.
A.3.7 Neurotoxicity
These studies are not required. Chlorflurenol methyl ester is neither an organic
phosphate nor shows evidence of neurotoxicity.
870.6100 Delayed Neurotoxicity Study - Hen
870.6200 Acute Neurotoxicity Screening Battery
870.6200 Subchronic Neurotoxicity Screening Battery
870.6300 Developmental Neurotoxicity Study
A.3.8 Metabolism
870.7485 Metabolism - Rat
144
-------
Not required, but an unacceptable study was submitted Study showed some
information, but study was inadequately replicated since most of the tests were conducted
in only one female rat.
EXECUTIVE SUMMARY: Kinetics and distribution of radiolabeled IT 3456, IT 3294
and IT 5733 [3 components of chlorflurenol methyl ester] were each assessed [MRTD
0082868]. The kinetic were conducted in 3 experiments. Experiment 1: One female
Wistar rat each was administered a single dose of 5 mg of IT 3456, IT 3294 or IT
5733/kg and the amount excreted n the urine and feces collected at 24 hours. Another set
of 3 females were dosed similarly and urine and feces collected at 72 hours and whole
body radio-autography conducted to located residual radiolabel. Experiment 2: One
lactating female/ test material was dosed with 10 mg/kg and 3 days later radio-
autography conducted to locate residual radiolabel. Experiment 3: One nursing dam with
10 pups/dam was dosed with 5 mg/kg and 3 days later radiolabel was counted in 2
pups/time period of 1, 2, 4 8 and 24 hours. Doses were administered in 0.5 mL
DMSO/kg by intravenously into the caudal vein in Experiment 1 and 3 and by gavage in
0.5 ml DMSO/kg in Experiment 2.
Each of all 3 test materials were excreted almost completely within 24 hours
primarily in the urine with lesser amounts in the feces; small amounts were excreted
between 24 and 72 hours. Enterohepatic circulation was noted. Most of the radiolabel
detected were in the lungs and kidney with small amounts of radiolabel detected in the
mammary gland in Experiment 2. Pups from Experiment 3 showed no measurable
radiolabeled test material.
Thus, each of all three test materials were rapidly excreted in the urine and
feces, with small amounts being seen in the mammary gland and none in the milk.
The study is UNACCEPTABLE/NG for a metabolism study in rodents. The study
results were no replicated and some of the data was not presented and/or readable and
thus conclusions were not verifiable. Test materials were inadequately identified.
Distribution of the radiolabel in the rats was not adequately quantified. The study may
have been a range-finding study.
COMPLIANCE: These studies were conducted in 1972 prior to GLP Guideline
requirements. No quality Assurance or Data Confidentiality Claim statements were
provided.
A.3.9 Dermal Absorption
870.7600 Dermal Absorption - Rat
A dermal absorption was not submitted.
A.4 References
145
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00082863 Frohberg, H.; Metallinos, A.; Pies, H.; et al. (1975) Chronic Toxicity Test
with IT 3456 in Beagle Dogs: Administration with the Food over a Period
of Two Years. (Translation; unpublished study received Apr 25, 1978
under 21137-EX-3; prepared by E. Merck, West Germany, submitted by
EM Laboratories, Inc., Elms- ford, N.Y.; CDL:097056-A).
00082865 Hofmann, A.; Weisse, G.; Kovac, W.; et al. (1976) IT 3456: 18-month
Carcinogenicity Study in Mice, Substance Administered in the Food:
Document No. CF 41 Ell6. (Unpublished study received Apr 25, 1978
under 21137-EX-3; prepared by E. Merck, West Germany, submitted by
EM Laboratories, Inc., Elmsford, N.Y.; CDL: 097058-A)
00082868 Wenzl, H.; Garbe, A.; Nowak, H. (1972) EMD-IT 3294; EMD-IT 5733;
EMD-IT 3456: Investigations of the Kinetics and Distribution in Rats:
Document No. CF 6/72. (Translation; unpublished study received Apr 25,
1978 under 21137-EX-3; prepared by E. Merck, West Germany, submitted
by EM Laboratories, Inc., Elmsford, N.Y.; CDL:097058-E)
00120883 Kohn, F.; Stahoviak, E.; Vega, S.; et al. (1970) Report to United States
Borax Research Corporation: 21-day Subacute Dermal Toxicity Study of
Maintain CF-125: Lifestream Laboratories Project No. 1385.
(Unpublished study received Jan 7, 1970 under 1624-8; prepared by
Lifestream Corp., submitted by United States Borax & Chemical Corp.,
Los Angeles, CA; CDL:108523-A)
43355402 Wnorowski, G. (1994) Acute Oral Toxicity Limit Test: (Chlorflurenol
Methyl): Lab Project Number: 3170. Unpublished study prepared by
Product Safety Labs. 16 p.
43355403 Wnorowski, G. (1994) Acute Dermal Toxicity Limit Test: (Chlorflurenol
Methyl): Lab Project Number: 2958. Unpublished study prepared by
Product Safety Labs. 15 p.
43355404 Wnorowski, G. (1994) Primary Eye Irritation: (Chlorflurenol Methyl): Lab
Project Number: 2605. Unpublished study prepared by Product Safety
Labs. 21 p.
43355405 Wnorowski, G. (1994) Primary Skin Irritation: (Chlorflurenol Methyl):
Lab Project Number: 2864. Unpublished study prepared by Product
Safety Labs. 16 p.
43361701 Wnorowski, G. (1994) Dermal Sensitization Test—Buehler Method:
(Chlorflurenol Methyl): Lab Project Number: 3035. Unpublished study
prepared by Product Safety Labs. 24 p. 43595402 Pant, K. (1995)
146
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Evaluation of a Test Article in the Salmonella typhimurium Plate
Incorporation Mutation Assay in the Presence and Absence of
Aroclor-Induced Rat Liver S-9: Chiorflurenol-Methyl: Lab Project
Number: 0336-2110: CFM-NITA-842A. Unpublished study prepared by
SITEK Research Labs. 49 p.
43562801 Thilagar, A. (1995) Test for Chemical Induction of Chromosome
Aberration in Cultured Chinese Hamster Ovary (CHO) Cells With and
Without Metabolic Activation: Final Report: Lab Project Number:
0336-3110: CFM-NITA-842B. Unpublished study prepared by Sitek
Research Labs. 59 p.
45137404 Timm, A. (1988) Unscheduled DNA Synthesis in Hepatocytes of Male
Rates in Vitro (UDS Test) with Chi orflurenol-Methyl, Technical: Lab
Project Number: 117033. Unpublished study prepared by CCR Cytotest
Cell Research GmbH & Co. KG. 30 p. (OPPTS 870.5550}
45137405 Heidemann, A. (1988) Detection of Gene Mutations in Mammalian Cells
in Vitro HGPRT Test with Chi orflurenol-Methyl, Technical: Lab Project
Number: 117022. Unpublished study prepared by CCR Cytotest Cell
Research GmbH & Co. KG. 34 p. {OPPTS 870.5300}
45147201 Moore, G. (2000) Acute Inhalation Toxicity Study in Rats-Limit Test:
Chlorflurenol-Methyl (ICA-MECFOL): Lab Project Number: 9125: P330.
Unpublished study prepared by Product Safely Labs. 24 p. {OPPTS
870.1300}
45190901 Muller, W. (2000) Chlorflurenol-Methyl, Technical Oral (Gavage)
Teratogenicity Study in the Rat: Lab Project Number: 926-460-028:
460-028. Unpublished study prepared by Hazleton Laboratories
Deutschland GmbH. 222 p.
45441001 Kuhn, J. (2001) 90-Day Oral Toxicity Study in Rats (Diet): Chi orflurenol
Methyl Ester: Final Report: Lab Project Number: 5472-99. Unpublished
study prepared by Stillmeadow, Inc. 136 p. {OPPTS 870.3100}
147
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Appendix K: Chlorflurenol Ecological and Fate and Effects Assessment
Environmental Fate
and Ecological Risk Assessment
for Chlorflurenol Methyl Ester Reregistration
Prepared by:
Jennifer Leyhe, M.S.
Larry Liu, Ph.D.
Reviewed by:
Karen Whitby, Ph.D.
148
-------
Table of Contents
I. Executive Summary 151
A. Nature of Chemical Stressor 151
B. Potential Risks to Non-target Organisms 152
C. Conclusions - Exposure Characterization 152
D. Conclusions - Effects Characterization 153
E. Data Gaps and Uncertainties 153
1. Environmental Fate 153
2. Ecological Effects 154
F. Summary of Endangered Species 154
II. Problem Formulation 155
A. Stressor Source and Distribution 156
1. Source and Intensity 156
2. Physicochemical, Fate, and Transport Properties 156
3. Pesticide Type, Class, and Mode of Action 157
4. Overview of Pesticide Usage 158
B. Receptors 158
1. Ecological Effects 158
a. Aquatic Effects 158
b. Terrestrial Effects 158
2. Ecosystems at Risk 158
C. Assessment Endpoints 159
D. Conceptual Model 160
1. Risk Hypotheses 160
2. Diagram 161
E. Analysis Plan 162
1. Methods for Conducting Ecological Risk Assessment and Identification of
Data Gaps 162
2. Measures to Evaluate Risk Hypotheses and Conceptual Model 164
a. Measures of Exposure 164
b. Measures of Effect 164
c. Measures of Ecosystem and Receptor Characteristics 165
III. Analysis 165
A. Use Characterization 165
B. Exposure Characterization 166
1. Environmental Fate and Transport Characterization 166
2. Measures of Aquatic Exposure 166
149
-------
a. Aquatic Exposure Modeling 167
b. Aquatic Exposure Monitoring (Field Data) 167
3. Terrestrial Exposure Assessment 167
a. Terrestrial Animal Exposure Modeling 167
b. Terrestrial Exposure Monitoring (Field Data) 169
4. Non-Target Plant Exposure Assessment 169
C. Ecological Effects Characterization 169
1. Aquatic Effects: Animals and Plants 169
2. Terrestrial Effects 169
a. Terrestrial Animals 170
b. Terrestrial Plants 171
IV. Risk Characterization 171
A. Risk Estimation - Integration of Exposure and Effects Data 171
1. Non-target Aquatic Animals and Plants 171
a. Acute and Chronic Risk to Animals 172
b. Aquatic Plants 172
2. Non-target Terrestrial Animals 172
a. Acute Risk to Birds and Mammals 172
b. Chronic Risk to Birds and Mammals 172
c. Risk to Terrestrial Invertebrates 173
3. Non-target Terrestrial and Semi-Aquatic Plants 173
B. Risk Description - Interpretation of Direct Effects 173
1. Risks to Aquatic Organisms 174
2. Risks to Terrestrial Organisms 174
a. Acute Risk to Birds and Mammals 174
b. Chronic Risk to Birds and Mammals 174
c. Non-target Terrestrial Invertebrates 175
d. Terrestrial Plants 175
3. Review of Incident Data 176
4. Endocrine Effects 176
5. Threatened and Endangered Species Concerns 177
a. Action Area 177
b. Taxonomic Groups Potentially at Risk 177
i. Discussion of Risk Quotients 179
ii. Probit Dose Response Relationship 180
c. Indirect Effects Analysis 180
d. Critical Habitat 182
e. Co-occurrence Analysis 184
C. Description of Assumptions, Limitations, Uncertainties, Strengths and Data
Gaps 184
1. Assumptions, Limitations, Uncertainties, Strengths and Data Gaps Related
to Exposure For All Taxa 184
2. Assumptions, Limitations, Uncertainties, Strengths and Data Gaps Related
to Exposure For Aquatic Species 185
150
-------
3. Assumptions, Limitations, Uncertainties, Strengths and Data Gaps Related
to Exposure For Terrestrial Species 185
a. Location of Wildlife Species 185
b. Routes of Exposure 186
c. Incidental Pesticide Releases Associated with Use 187
d. Residue Levels Selection 187
e. Dietary Intake - The Differences Between Laboratory and Field
Conditions 187
4. Assumptions, Limitations, Uncertainties, Strengths and Data Gaps Related
to Effects Assessment 188
a. Age Class and Sensitivity of Effects Thresholds 189
b. Lack of Effects Data for Amphibians and Reptiles 189
c. Use of the Most Sensitive Species Tested 190
5. Assumptions, Limitations, Uncertainties, Strengths and Data Gaps Related
to the Acute and Chronic LOCs 190
V. Literature Cited 191
I. Executive Summary
A. Nature of Chemical Stressor
Chlorflurenol methyl ester (ME) is used as an herbicide and plant growth regulator to control
perennial and annual weeds and grasses. It is applied to ornamentals, hedge and fence rows, turf,
shade trees, woody shrubs, and vines, and also is used to produce planting material for
pineapples. It is formulated as an emulsifiable concentrate, which is applied as a spray; or as a
granule, which is broadcast with a spreader. Chlorflurenol ME penetrates into herbaceous plants
(via foliage and/or roots) and moves freely inside the plant (aero and basipetal transport). Growth
and development of growing tips and buds of herbaceous plants are blocked or slowed down.
Chlorflurenol ME consists of three components. The major component is methyl 2-chloro-9-
hydroxyfluorene-9-carboxylate (PC code 098801). The minor components are methyl 2,7-
dichloro-9-hydroxyfluorene-9-carboxylate (PC code 098803) and methyl 9-hydroxyfluorene-9-
carboxylate (PC code 098802). The latter (PC code 098802) is used as the starting material for
the production of the major component (PC code 098801) and the former (PC code 098803) is
obtained as a byproduct during the manufacture of the latter compound (PC code 098802). Since
the chemical structures for these two minor components are very similar to that of the major
component, it is reasonable to believe that they all have herbicidal activity. According to the
registrant, these three components are inseparable and are synthesized in a relatively constant
ratio. For example, the ratio among PC code 098801, PC code 098802, and PC code 098803 on
the label EPA Reg. No. 69361-1 are 5.6:1.4:1 whereas the corresponding ratio on the label EPA
Reg. No. 69361-6 are 5.5:1.3:1. As a result, although many environmental fate and ecological
studies stated that methyl-2-chloro-9-hydroxyfluorene-9-carboxylate (the major component) was
used as the test substance, EFED assumed that a mixture of all three components was used.
Therefore, this ecological risk assessment is based on this assumption.
The environmental persistence of Chlorflurenol ME is difficult to determine with any certainty
due to the limited number of studies available, and the deficiencies within these studies. Based
151
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on these limited data, chlorflurenol ME appears to be highly to very highly mobile in soil, and
hydrolytically stable at pH 6. The study submitted by the registrant in order to fulfill the aerobic
soil metabolism data requirements was determined to be unacceptable because the study was
conducted outdoors. However, since this aerobic soil metabolism study could be considered
supplemental as a small-scale quasi field dissipation study, its results could be interpreted
qualitatively. Chlorflurenol ME appears to degrade rapidly under field conditions.
B. Potential Risks to Non-target Organisms
This is the Environmental Fate and Effects Division's (EFED) national screening-level ecological
risk assessment for the proposed re-registration of chlorflurenol ME. Table 1 summarizes the
major conclusions and uncertainties of this assessment for aquatic and terrestrial receptors. The
results suggest the potential for acute risk to listed terrestrial birds, reptiles, and mammals, and
chronic risk to mammals. In addition, there is the potential for acute risk to non-listed terrestrial
birds and reptiles from restricted use applications. Functionally, the estimated risks may translate
to reduced survival and reproduction of impacted species with subsequent effects at higher levels
of biological organization.
Acute and chronic risk to all aquatic invertebrates, fish, and terrestrial invertebrates, and
chronic risk to birds cannot be precluded because data are not available. In addition, data
are unavailable for aquatic and terrestrial plants; however, since chlorflurenol ME is used
as an herbicide/plant growth regulator, risk to aquatic vascular and non-vascular plants
and non-target terrestrial and semi-aquatic plants is expected.
Table 1. Summary of Environmental Risk Conclusions for Aquatic and Terrestrial
Organisms and Plants exposed to Chlorflurenol ME.
Acute and Chronic Risk to Freshwater
and Estuarine/marine Fish and
Invertebrates
Risk to Aquatic Vascular and Non-
Vascular Plants
Acute Risk to Birds
Chronic Risk to Birds
Acute Risk to Mammals
Chronic Risk to Mammals
Terrestrial Plants
Non-target Invertebrates
Risk could not be precluded due to lack of data.
Risk could not be precluded due to lack of data.
Definitive acute dose-based RQ values for avian receptors could not be
derived because there are no definitive LD50 values.
Risk could not be precluded due to lack of data.
Definitive acute dose-based RQ values for mammalian receptors could not be
derived because there are no definitive LD50 values.
The reported RQ values are above the chronic LOG (1.0) for species that feed
on short grass, tall grass, and broadleaf plants/small insects (RQ range = 0.02
to 2. 90).
Risk could not be precluded due to lack of data.
Risk could not be precluded due to lack of data.
C. Conclusions - Exposure Characterization
The registrant has submitted three studies to fulfill the environmental fate data requirements;
however, these studies were considered to be either supplemental or unacceptable. As a result,
the analysis could not be performed with confidence. No aquatic modelling was conducted due to
lack of fate and toxicity data.
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To estimate exposure of terrestrial animals, terrestrial EECs were generated using the Tier 1
model T-REX for chlorflurenol ME spray use based on maximum application rates and use
patterns. Granular application was not assessed. For foliar spray applications, EECs and acute
and chronic RQs were estimated for residues on various forage categories (short grass, tall grass,
broadleaf plants/small insects, fruits/pods/large insects, and seeds). Chlorflurenol ME
concentrations were highest on the surfaces of short grass and lowest on the surfaces of fruits,
pods, and large insects.
D. Conclusions - Effects Characterization
Results of acute toxicity studies on birds suggest that chlorflurenol ME is practically nontoxic on
an acute oral basis (LD50 > 10,000 mg a.i./kg body weight) and practically nontoxic on an acute
dietary basis (LC50 >5,000 mg a.i./kg diet). Mammalian data suggest that chlorflurenol ME is
practically nontoxic (LD50 >5,000 mg a.i./kg body weight) on an acute oral basis.
A chronic toxicity study with rats showed that the maternal NOAEL was 250 mg/kg bw/day. The
maternal LOAEL is 750 mg/kg bw/day based on body weight gain decrement and nominally
decreased food efficiency. The developmental NOAEL is 250 mg/kg bw/day. The developmental
LOAEL is 750 mg/kg bw/day, based on treatment-related delayed ossification in skull bones
(nasal and frontal) in fetuses and litters.
No quantitative data are available to characterize risks from exposure of chlorflurenol ME to
freshwater and estuarine/marine fish and invertebrates (acute and chronic risk), birds (chronic
risk), and aquatic and terrestrial plants. EFED cannot preclude risk to these taxa. In addition,
since chlorflurenol ME is used as an herbicide or a plant growth regulator, risk to non-target
plants is expected.
E. Data Gaps and Uncertainties
The screening-level assessment for chlorflurenol ME has been conducted despite unfulfilled
guideline requirements and existing environmental fate and ecological data gaps (Tables HI and
H2, Appendix H). The following is a brief synopsis of the major environmental fate and
ecological effects data gaps and uncertainties. Additional detail can be found in Section IV C,
Description of Assumptions, Limitations, Uncertainties, Strengths and Data Gaps.
1. Environmental Fate
• Guideline 161-1 Hydrolysis (the submitted study (MRID 43496201) was determined to
be supplemental and the hydrolysis data requirements have not been fulfilled. A new
study including pH 7 is required)
• Guideline 161-2 Aqueous photolysis
• Guideline 161-3 Soil photolysis
• Guideline 162-1 Aerobic soil metabolism (the submitted study (MRID 43595403) was
determined to be unacceptable. A new study using four soils is required)
• Guideline 162-2 Anaerobic soil metabolism
• Guideline 162-3 Anaerobic aquatic metabolism
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• Guideline 163-1 Adsorption/desorption (the submitted study (MRID43496202) was
determined to be supplemental and the adsorption/desorption data requirements have not
been fulfilled. A new study including three soils is required)
• Guideline 164-1 Terrestrial field dissipation
• Guideline 165-4 Fish bioaccumulation
• Guideline 201-1 Droplet Size Spectrum (a waiver request was denied by EPA on 3/2/05)
• Guideline 202-1 Drift Field Evaluation (a waiver request was denied by EPA on 3/2/05)
2. Ecological Effects
• Guidelines 72-1, 72-2, 72-3, 72-4: Acute and chronic data for freshwater and
estuarine/marine fish and invertebrates are not available; therefore risk could not be
assessed.
• Guideline 71-4: There are no avian reproduction studies available; therefore risk could
not be assessed.
• Guideline 123-1, 123-2: Terrestrial Plant Seedling Emergence and Vegetative Vigor
studies are not available. In addition, aquatic plant growth studies are not available;
therefore risk could not be assessed. Since chlorflurenol ME is used as an herbicide and
growth regulator, toxicity data on non-target plants are necessary to estimate risk.
Available literature suggests that chlorflurenol causes reproductive effects in terrestrial
plants.
• Guideline 141-1: Honey Bee Acute Contact Toxicity; no data are available; therefore risk
could not be assessed.
• Acute oral and dietary toxicity studies in birds and acute oral toxicity to mammals failed
to establish definitive acute LD50/LC50 values (i.e., the LC50 was expressed as "greater
than" the highest dietary concentration tested); thus, acute RQ could not be calculated.
• The study testing oral toxicity to birds did not state which components were included in
the test material. EFED assumes the test material contained all three components which
may underestimate risk to birds on an acute oral basis if in fact the test material only
contained one of the three components.
• The mammalian chronic RQs are based on a developmental study that shows evidence of
delayed skull ossification and cleft palates in young rats. These endpoints are not
adequate for determining risk to the survival and fecundity of a population. However,
without other studies EFED used these data. Therefore, the RQs may not accurately
portray chronic risk to mammals. Risk may be under- or over-estimated.
• Application interval and number of applications per year are not indicated on the label.
For multiple application scenarios, the T-Rex model requires both of these parameters in
order to estimate exposure to terrestrial organisms. In the absence of these numbers an
application interval of 28 days and 8 applications per year (as derived by HED, Appendix
B) were used. HED used information provided on the labels along with their best
professional judgment of the crop/weed growth cycles, pest pressure timing, etc. to
determine the application interval and yearly number of applications. EFED used the
HED data to maintain consistency between EFED and HED. Since these numbers are
considered "likely" applications per year, risk to terrestrial organisms may be
underestimated.
F. Summary of Endangered Species
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Table 2 summarizes the potential risk to listed species associated with the application of
chlorflurenol. For all taxa except acute risk to birds and mammals and chronic risk to mammals,
risk is presumed to occur due to lack of data.
Table 2. Listed species risks associated with direct or indirect effects due to applications
of chlorflurenol for turf use.
Listed Taxon
Terrestrial and semi-aquatic plants -
monocots
Terrestrial and semi-aquatic plants -
dicots
Insects
Birds
Terrestrial phase amphibians
Reptiles
Mammals
Aquatic vascular plants
Freshwater fish
Aquatic phase amphibians
Freshwater crustaceans
Mollusks
Marine/estuarine fish
Marine/estuarine crustaceans
Direct Effects
Yes"
Yes"
Yesa
Acute - Yes c; Chronic - Yes a
Yesa
Acute - Yes c; Chronic - Yes a
Acute - Yes c; Chronic - Yes b
Yesa
Yesa
Yesa
Yesa
Yesa
Yesa
Yesa
Indirect Effects
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
a We cannot preclude risk due to lack of data.
b The reported RQ values are above the chronic LOG (1 .0) for species that feed on short grass, tall grass, and broadleaf
plants/small insects (RQ range = 0.02 to 2.90).
cRQs could potentially exceed acute listed species LOCs unless the actual LD50 values are established in laboratory
studies to be greater than —16,715 mg a.i./kg body weight or if the amount available in the environment was lowered
below 500 ppm
II. Problem Formulation
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A. Stressor Source and Distribution
1. Source and Intensity
Chlorflurenol ME formulations are currently registered for use on turf, fencerows, hedgerows,
rights-of-ways, forests, industrial areas, recreational areas, and pineapples as ground or aerial
sprays. The rates of application range from 0.25 to 3.0 Ib a.i./acre with no maximum number of
applications/season and no set interval between applications specified on the label.
2. Physicochemical, Fate, and Transport Properties
Chlorflurenol ME is used as an herbicide and plant growth regulator. It consists of three
components (see table below). The major component is methyl 2-chloro-9-hydroxyfluorene-9-
carboxylate (PC code 098801). The minor components are methyl 2,7-dichloro-9-
hydroxyfluorene-9-carboxylate (PC code 098803) and methyl 9-hydroxyfluorene-9-carboxylate
(PC code 098802). The latter (PC code 098802) is used as the starting material for the production
of the major component (PC code 098801) and the former (PC code 098803) is obtained as a
byproduct during the manufacture of the latter compound (PC code 098802). Since the chemical
structures for these two minor components are very similar to that of the major component, it is
reasonable to believe that they all have herbicidal activity. According to the registrant, these
three components are inseparable and are synthesized in a relatively constant ratio. For examples,
the ratio among PC code 098801, PC code 098802, and PC code 098803 on the label EPA Reg.
No. 69361-1 are 5.6:1.4:1 whereas the corresponding ratio on the label EPA Reg. No. 69361-6
are 5.5:1.3:1. As a result, although many environmental fate and ecological studies stated that
methyl-2-chloro-9-hydroxyfluorene-9-carboxylate (the major component) was used as the test
substance, EFED assumed that a mixture of all three components was used. Therefore, this
ecological risk assessment is based on this assumption.
Chlorflurenol ME
A mixture of 65-70% methyl-2-chloro-9-hydroxyfluorene-9-carboxylate,
10-15% methyl-2,7-dichloro-9-hydroxyfluorene-9-carboxylate and 15-20%
methyl-9-hydroxyfluorene-9-carboxylate.
R3
Methyl-2-chloro-9-hydroxyfluorene-9-carboxylate; RI = Cl; R2 = H; R3 = CH3
Methyl-2,7-dichloro-9-hydroxyfluorene-9-carboxylate; RI = R2 = Cl; R3 = CH3
Methyl-9-hydroxyfluorene-9-carboxylate; RI = R2 = H; R3 = CH3.
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No information on the physical and chemical properties could be found for those two minor
components (PC codes 098802 and 098803). Limited information was found for the major
component (PC code 098801), which has very low water solubility and is moderately volatile:
Common Name: Chlorflurenol ME
Chemical Name (IUPAC):
(RS)-2-Chloro-9-hydroxyfluorene-9-carboxylic acid methyl ester
Chemical Name (CAS):
2-Chloro-9-hydroxy-9H-fluorene-9-carboxylic acid methyl ester
CAS No.: 2536-31-4
PC Code: 098801
Molecular Formula: C15H11C1O3
Molecular Weight: 274.7g/mol
Vapor Pressure (temperature unknown): 2.5 x 10-5 torr
Water Solubility (temperature and pH unknown): 21.8 ppm
The environmental persistence of chlorflurenol ME is difficult to determine with any certainty
due to the limited number of studies available, and the deficiencies within these studies. Based
on these limited data, chlorflurenol ME appears to be highly to very highly mobile in soil, and
hydrolytically stable at pH 6. The study submitted by the registrant in order to fulfill the aerobic
soil metabolism data requirements was determined to be unacceptable because the study was
conducted outdoors. However, since this aerobic soil metabolism study could be considered
supplemental as a small-scale quasi field dissipation study, its results could be interpreted
qualitatively. Chlorflurenol ME appears to degrade rapidly under field conditions. Efforts were
made; however, no chemicals which have similar chemical structures as chlorflurenol ME were
found.
Chlorflurenol ME degraded by hydrolysis with a half-life of 161.2 days and 0.2 days at pHs 6 and
9, respectively. The most environmentally relevant pH of 7 for aquatic systems was not tested.
At study termination, 77.8% (50 days, pH 6), 55.6% (0.19 days, pH 9) and 41.7% (0.29 days, pH
9) of the applied chlorflurenol ME was undegraded. The major transformation product was 2-
chloro-9-hydroxyfluorene-9-carboxylic acid; however, quantitative data and further details were
not reported.
Chlorflurenol ME degraded in sandy loam soil (pH 6.0) in outdoor plots with a half-life of 1.3
days. Chlorflurenol ME was completely degraded by 26 days (study termination). One major
degradation product was detected, 2-chloro-9-fluorenone at a maximum of 14.3% of the applied
at 5-12 days and was not detected at 26 days.
In laboratory mobility studies, chlorflurenol ME was highly to very highly mobile in a sandy
loam soil from Germany.
3. Pesticide Type, Class, and Mode of Action
Chlorflurenol ME is used as an herbicide and plant growth regulator. It consists of three
components. The major component is methyl 2-chloro-9-hydroxyfluorene-9-carboxylate (II).
The minor components are methyl 2,7-dichloro-9-hydroxyfluorene-9-carboxylate (III) and methyl
9-hydroxyfluorene-9-carboxylate (I). The latter (I) is used as the starting material for the
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production of the major component (II) and the former (III) is obtained as a byproduct during the
manufacture of the latter compound (I). This chemical readily penetrates into herbaceous plants
(via foliage and/or roots). It moves freely inside the plant (aero and basipetal transport). Growth
and development of growing tips and buds of herbaceous plants are blocked or slowed down as a
result of chlorflurenol ME usage. EFED could not find information on the mode of action for this
chemical.
4. Overview of Pesticide Usage
There are no data on the actual usage of chlorflurenol ME.
B. Receptors
1. Ecological Effects
Each assessment endpoint requires one or more measures of ecological effect, which are defined
as changes in the attributes of an assessment endpoint itself or changes in a surrogate entity or
attribute in response to exposure to a pesticide. Ecological measures of effect for this screening-
level risk assessment are based on a suite of registrant-submitted toxicity studies performed on a
limited number of organisms in broad groupings. A complete discussion of all toxicity data
available for this risk assessment and the resulting measures of effect selected for each taxonomic
group are included in Appendix D.
a. Aquatic Effects
Toxicity data sufficient for use in a risk assessment for chlorflurenol ME are not available for
freshwater fish and invertebrates, estuarine/marine fish and invertebrates, algae, and vascular
plants. No studies on chlorflurenol ME are available for acute or chronic exposure for any of
these taxa. In addition, since there are very limited fate data, no aquatic exposure models were
run. Therefore, risk cannot be precluded.
b. Terrestrial Effects
Registrant-submitted laboratory studies on chlorflurenol ME formulations are available for acute
exposure of birds and mammals. In addition chronic studies have been submitted for mammals
but not for birds. No toxicity studies on the effects of chlorflurenol ME on terrestrial plants or
honeybees were submitted. Details of all registrant and open literature studies are provided in
Appendix D. Where data are lacking, risk could not be precluded.
2. Ecosystems at Risk
Ecosystems potentially at risk are expressed in terms of the selected assessment measures of
effect. The typical assessment measures of effect for screening-level pesticide ecological risk
assessments are reduced survival and reproductive and growth impairment for both aquatic and
terrestrial animal species. Aquatic animal species of potential concern include freshwater fish
and invertebrates, estuarine/marine fish and invertebrates, and amphibians. Terrestrial animal
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species of potential concern include birds, mammals, reptiles, and beneficial insects. For both
aquatic and terrestrial animal species, acute and chronic exposures are considered.
C. Assessment Endpoints
This risk assessment considers the maximum application rate of chlorflurenol ME spray (granular
was not assessed) on vulnerable soils as reported on the label, the likely number of applications as
derived by HED (Appendix B), and the likely application intervals as reported by HED
(Appendix B) to estimate exposure concentrations as a result of the use of chlorflurenol ME.
This assessment is not intended to represent a site or time-specific analysis. Likewise, the most
sensitive toxicity endpoints are used from surrogate test species to estimate treatment-related
direct effects on acute mortality and chronic reproductive, growth and survival assessment
endpoints. Surrogate aquatic organisms include freshwater and saltwater fish and invertebrates.
In the absence of toxicity data on amphibians, it is assumed that aquatic-phase amphibians are
approximately as sensitive as fish to potential effects of a pesticide. Surrogate terrestrial animal
species include birds and mammals. The risk assessment also assumes that reptiles and
terrestrial-phase amphibians are approximately as sensitive to pesticide-induced effects as birds.
These tests include short-term acute, subacute, and reproduction studies and are typically
arranged in a hierarchical or tiered system that progresses from basic laboratory tests to applied
field studies.
For plants in terrestrial and semi-aquatic environments, the screening assessment endpoint is the
perpetuation of populations of non-target species (crops and non-crop plant species). Endpoints
assessed include emergence of seedlings and vegetative vigor. Although it is recognized that the
endpoints of seedling emergence and vegetative vigor may not address all plant life cycle
components, it is assumed that impacts at emergence and in active growth have the potential to
impact individual competitive ability and reproductive success. For aquatic plants, the
assessment endpoint is the maintenance and growth of standing crop or biomass.
In order to protect federally endangered and threatened (listed) species, all assessment endpoints
are measured at the individual level. They also provide insight about risks at higher levels of
biological organization (e.g. populations and communities). For example, pesticide effects on
individual survivorship have important implications for both population rates of increase and
habitat carrying capacity.
The ecological relevance of selecting the above-mentioned assessment endpoints is as follows: 1)
complete exposure pathways exist for these receptors; 2) the receptors may be potentially
sensitive to pesticides in affected media and in residues on plants, seeds, and insects; and 3) the
receptors could potentially inhabit areas where pesticides are applied, or areas where runoff
and/or spray drift may impact the sites because suitable habitat is available.
The toxicity studies are used to evaluate the potential of chlorflurenol ME to cause adverse
effects, to determine whether further testing is required, and to determine the need for
precautionary label statements to minimize the potential adverse effects to non-target animals and
plants (40 CFR §158.202, 2002). A summary of the assessment endpoints and measures of effect
selected to characterize potential ecological risks associated with exposure to chlorflurenol ME is
provided in Table 3.
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Table 3. Summary of Assessment Endpoints and Measures of Effect for
Chlorflurenol ME.
Assessment Endpoint
1. Abundance (i.e., survival, reproduction,
and growth) of individuals and populations
of birds.
2. Abundance (i.e., survival, reproduction,
and growth) of individuals and populations
of mammals.
3. Survival and reproduction of individuals
and communities of freshwater fish and
invertebrates.
4. Survival and reproduction of individuals
and communities of estuarine/marine fish
and invertebrates.
5. Survival of terrestrial invertebrate
populations (beneficial insects and
earthworms).
Measure of Effect
la. Bobwhite quail acute oral LD50
(guideline-recommended species).
Ib. Bobwhite quail subacute dietary LCso
(guideline-recommended species).
Ic. Avian chronic/reproduction: data gap
2a. Laboratory rat acute oral LD50.
2b. Rat developmental NOAEL
3a. Rainbow trout and bluegill sunfish
acute LCso : data gap
3b. Water flea acute LCso: data gap
3c. Freshwater fish chronic: data gap
3d. Freshwater invertebrate chronic: data
gap
4a. Estuarine/marine fish acute: data gap
4b. Estuarine/marine invertebrate acute:
data gap
4c. Estuarine/marine fish chronic: data gap
4d. Estuarine/marine invertebrate chronic:
data gap
5a. Honeybee acute contact LD50: data gap
LD50 = Lethal dose to 50% of the test population.
LC50 (EC50) = Lethal (effective) concentration to 50% of the test population.
D. Conceptual Model
1. Risk Hypotheses
Risk hypotheses are specific assumptions about potential adverse effects (i.e., changes in
assessment endpoints) and may be based on theory and logic, empirical data, mathematical
models, or probability models (US EPA 2004). For this assessment, the risk is stressor-initiated,
where the stressor is the release of chlorflurenol ME spray to the environment. The following
risk hypothesis is presumed for this screening-level assessment:
Non-target aquatic and terrestrial plants and animals may be exposed to chlorflurenol
ME when it is applied in agricultural and/or non-agricultural settings to control
unwanted plants. Based on available information regarding the persistence, mode of
action, direct and indirect toxicity, chlorflurenol ME may have the potential to
compromise growth, reproduction, and/or survival of non-target terrestrial and aquatic
animals and plants.
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Ecological receptors that may potentially be exposed to chlorflurenol ME and its transformation
products include terrestrial and semi-aquatic wildlife (i.e., mammals, birds, amphibians, and
reptiles), terrestrial and semi-aquatic plants, and soil invertebrates. In addition, aquatic receptors
(e.g., freshwater and estuarine/marine fish and invertebrates, and amphibians) may also be
exposed as a result of potential migration of chlorflurenol ME via spray drift and/or
runoff/erosion from the site of application to various watersheds and other aquatic environments.
These data formed the basis for identifying potential endpoints, stressors, and ecological effects
associated with uses of chlorflurenol ME.
2. Diagram
Based on the preliminary iterative process of examining fate and effects data, the conceptual
model or the risk hypothesis model for spray application to non-agricultural crops and pineapples
has been established, refined and included in Figure 1. Granular application was not assessed.
In establishing the diagram for the conceptual model it was necessary to go through an iterative
process to identify: (1) likely stressors/exposure pathways and (2) organisms that are most
relevant and applicable to this assessment.
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Stressor
Source/
Transport
Pathways
Chlorflurenol applied as ground/aerial spray to turf, forests, recreational areas,
industrial areas, right-of-ways, pineapples
t
1 Volatilization |
| /Wind !
| Suspension j
t
1 Direct
I Deposition
| (Parent)
t
1 Spray i
| Drift I
| (Parent) j
t
I Runoff/ |
I Erosion j
| (Parent + Deg) j
t
Leaching
Infiltration/Percolation
(Parent + Deg)
Source/
Exposure
Media
Exposure
Point
Receptors
Attribute
Changes
R
I Terrestrial Non-Food ! Upland ] ! Ripe
| Residues (foliage, fruit, j Foliage/Soil | j Wet
i insects)
I
1! Foliac
:r:
rian/ | ! Water Column, U— 1 Groundwater ]
land I ! Sediment |
e/Soil i / i
s' \ \ Food Web i
^r T 1 — •
* : "* ^^~ 1 ('nil I/ 1 ntpn 1 1 mp nt r^xuu t>u i c
| lngestion& Dermal | Direct contact and root uptake |, ,^_ Jln_ti_ (Bioconcentration) !
i Uptake
\
Terrestrial Organisms
Birds, Mammals,
Reptiles, Terrestrial
Insects
(
Individual Animals
Reduced survival
Reduced growth
educed reproduction
j
i i
; : ;
Terrestrial j j Wetland/ j
Upland j j Riparian i
Plants 1 | Plants !
/-
1 InrlK/irliiol Plant" ^ = riant P
| Seedling emergence 1 \ Ke<
I Vegetative vigor I j pop
• 9 r
::: f 3^"
: 1 \ ^S^ I
• Annatir : ». **£~T. :
i ACluailc = ; Aquatic i J Piscivorous
i j j , _i i. * M Vertebrates
I Invertebrates i i
land Vertebrates! ! (Birds and
! Amphibians i 1 mammals)
1 1
juced j 1 Individual Animals j
jlatjon 1 ! Reduced survival ]
owth | i Reduced growth j
i Reduced i
i reproduction j
Dotted lines represent no data available
Figure 1. Ecological conceptual exposure model for chlorflurenol.
E. Analysis Plan
1. Methods for Conducting Ecological Risk Assessment and Identification of Data
Gaps
The primary method used to assess risk in this screening-level assessment is the risk quotient
(RQ) and follows closely methods outlined in the EPA Overview Document (US EPA, 2004).
The RQ is the primary risk value for the screening-level assessment and is the result of comparing
measures of exposure to measures of effect. A commonly used measure of exposure is the
estimated exposure concentration (EEC) and commonly used measures of effect include toxicity
values such as the LD50 or NOAEC. Assessment endpoints and their respective measures of
effect are listed in Table 3. The resulting RQ is then compared to a specified level of concern
(LOC), which represents a point of departure for concern; if the RQ exceeds the LOC, then risks
are triggered. Although not necessarily a true estimate of risk since there is no estimated
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probability of effect, in general, the higher the RQ, the more certain the potential risks. Risk
presumptions, along with the corresponding RQs, equations, and LOCs are summarized in
Appendix E.
Levels of concern (LOG) are the policy tool for interpreting risks from direct pesticide effects and
have a magnitude, duration, frequency, and spatial extent. The magnitude is set by the risk
presumption for each endpoint. The frequency of potential risk is once every ten years for aquatic
endpoints and reasonable upper bound for terrestrial risk. The spatial extent is defined by the use
area, and the areas downstream and areas potentially affected by spray drift.
Generation of robust RQs is dependent on the quality of data from both fate and toxicological
studies. The adequacy of the submitted data was evaluated relative to Agency guidelines. The
following identified data gaps for ecological fate and toxicity endpoints result in a degree of
uncertainty in evaluating the ecological risk of chlorflurenol ME.
For fate and transport, Table HI (Appendix H) lists the status of the fate and transport data
requirements for chlorflurenol ME. The adequacy of the submitted data was evaluated relative to
Agency guidelines. Data gaps identified for fate and transport include
• Guideline 161-1 Hydrolysis
• Guideline 161-2 Aqueous photolysis
• Guideline 161-3 Soil photolysis
• Guideline 162-1 Aerobic soil metabolism
• Guideline 162-2 Anaerobic soil metabolism
• Guideline 162-3 Anaerobic aquatic metabolism
• Guideline 163-1 Adsorption/desorption
• Guideline 164-1 Terrestrial field dissipation
• Guideline 165-4 Fish bioaccumulation
• Guideline 201-1 Droplet Size Spectrum
• Guideline 202-1 Drift Field Evaluation
For the ecological assessment, Table H2 (Appendix H) lists the status of ecological data
requirements for chlorflurenol ME. Hereunder is a summary of identified data gaps and
associated uncertainties:
• Guidelines 72-1, 72-2, 72-3, 72-4: Acute and chronic data for freshwater and
estuarine/marine fish and invertebrates are not available; therefore risk could not be
assessed.
• Guideline 71-4: Avian reproduction studies are not available; therefore risk could not be
assessed.
• Guideline 123-1 (a, b), 123-2: Terrestrial plant seedling emergence and vegetative vigor
studies are not available. In addition, aquatic plant growth studies are not available;
therefore risk could not be assessed. Since chlorflurenol ME is used as an herbicide and
growth regulator, toxicity data on non-target plants are necessary to estimate risk.
• Guideline 141-1: Data for honey bee acute contact toxicity are not available; therefore
risk could not be assessed.
• Acute oral and dietary toxicity studies in birds and acute oral toxicity studies in mammals
failed to establish definitive acute LD50/LC5o values (i.e., the LD50/LC5o were expressed
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as "greater than" the highest concentration tested); thus, acute RQ could not be
calculated.
• The mammalian chronic RQs are based on a developmental study that shows evidence of
delayed skull ossification and cleft palates in young rats. These endpoints are not
adequate for determining risk to the survival and fecundity of a population. However,
without other studies EFED used these data. Therefore, the RQs may not accurately
portray chronic risk to mammals. Risk may be under- or over-estimated.
2. Measures to Evaluate Risk Hypotheses and Conceptual Model
a. Measures of Exposure
Due to the absence of fate data and aquatic toxicity data, no aquatic exposure modeling was
conducted for this assessment. Exposure was assumed to occur.
Measures of exposure for terrestrial mammals, birds, reptiles and amphibians incorporate
maximum proposed use rates but rely less on fate properties. Terrestrial exposures were estimated
using a number of methods. Acute and chronic terrestrial exposure estimates are derived directly
from empirically determined observations of pesticide residues on various terrestrial food items.
The Kenaga nomogram, as modified by Fletcher et al., (Hoerger and Kenaga, 1972; Fletcher et
al., 1994) is used to relate pesticide application rates to residues on terrestrial food items. The
surface residue concentration (ppm) is estimated by multiplying the application rate (pounds
active ingredient (a.i.) per acre) by a value specific to each food item. For multiple applications of
a given use, the exposure model incorporates a first-order decay rate dependent on the foliar
dissipation half-life of the chemical. In the absence of data, a default foliar dissipation half-life of
35 days is used. The T-REX model was run for chlorflurenol ME turf use with the maximum
proposed application rate (3.0 Ib a.i./A; as stated on the label), a maximum of 8 applications
(HED derived with best professional judgment, see Appendix B), and a 28-day application
interval (HED derived with best professional judgment, see Appendix B) to assess risk to
terrestrial organisms. EFED used the HED data to maintain consistency between EFED and
HED. The conceptual approach taken to estimate residues (upper-bound and mean) on potential
dietary sources for mammals and birds is presented in the model T-REX Version 1.2.3 (T-REX,
2005)(For more details see Appendix C and the Exposure Characterization section of this
document).
b. Measures of Effect
Measures of ecological effects are obtained from a suite of registrant-submitted guideline studies
conducted with a limited number of surrogate species. The test species are not intended to be
representative of the most sensitive species but rather were selected based on their ability to
thrive under laboratory conditions. Measures of effect are based on deleterious changes in a
receptor as a result of chemical exposure. Functionally, measures of effect typically used in risk
assessments include changes in survival, reproduction, or growth as determined from standard
laboratory toxicity tests. The focus on these effects for quantitative risk assessments is due to
their clear relationship to higher-order ecological systems such as populations, communities, and
ecosystems. Monitoring data may also be used to provide supporting lines of evidence for the
risk characterization. In addition, although effects other than survival, reproduction, and growth
may be considered, rarely are they used quantitatively to estimate risks since, in many cases, the
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relationship between these effects and higher-order processes is tenuous at best. Commonly used
laboratory-derived toxicity values include estimates of acute mortality (e.g., LD50, LC50, or
EC50) and estimates of effects due to longer term, chronic exposures (e.g., NOAEC, NOAEL).
The latter can reflect changes seen in mortality, reproduction, or growth. In general, for a given
assessment endpoint the lowest relevant measure of effect is used when calculating the RQ.
Since preliminary review of the available ecological effects data suggests that chlorflurenol ME is
practically nontoxic to birds and mammals on an acute exposure basis, acute effects to non-listed
birds and mammals are not expected. Chronic exposure studies indicate that mammals may be at
chronic risk; no chronic avian toxicity data are available. No guideline data are available for
aquatic species, terrestrial plants, and insects. However, there are literature studies that show
reproductive effects on terrestrial plants.
A search of the open literature using EPA's Ecotoxicology database, ECOTOX, was conducted to
identify studies to fill the data gap for acute and chronic exposure of chlorflurenol ME to aquatic
fish and invertebrates, terrestrial invertebrates; search of the ECOTOX database did not identify
studies to fill these data gaps. The ECOTOX search did identify additional chronic toxicity
studies on the following: terrestrial plants (See section IV.B.2.d).
c. Measures of Ecosystem and Receptor Characteristics
The ecosystems selected for modeling, using T-REX for the Tier 1 terrestrial animal assessment,
are intended to be generally representative of any aquatic or terrestrial ecosystem associated with
areas where chlorflurenol ME is used. The receptors addressed by the aquatic and terrestrial risk
assessments are summarized in Table 3. For aquatic assessments, generally fish and aquatic
invertebrates in both freshwater and estuarine/marine environments are represented, when
available. For terrestrial assessments, mammals are represented by three different size classes
and five potential foraging categories (short grass, tall grass, broadleaf plants/small insects,
fruits/pods/seeds/large insects, and seeds). For the three different size classes of small birds, four
potential foraging categories are considered (short grass, tall grass, broadleaf plants/small insects,
and fruits/pods/seeds/large insects). For terrestrial plants, generally both dicots and monocots are
represented. Detailed information regarding the data available for these various classes of
aquatic and terrestrial receptors is provided in Appendix D.
III. Analysis
A. Use Characterization
Chlorflurenol ME [(RS)-2-chloro-9-hydroxyfluorene-9-carboxylic acid methyl ester; CF 125,
12.5% a.i.] is an herbicide/plant growth regulator (PGR) used to control weeds and grasses for
ornamentals, hedge and fence rows, turf, shade trees, woody shrubs and vines, and is specifically
used to produce planting material for pineapple production. The maximum application rate is 3 Ib
a.i./A for ornamental lawns, turf, and non-agricultural right-of-ways, fencerows, and hedgerows;
1 Ib a.i./lOO gal for shade trees (due to lack of information, EFED is unable to convert it to Ib
ai/A), woody shrubs and vines, forest conifers and junipers, recreational areas and industrial areas
(outdoors); and 1.0875 Ib a.i./A for pineapples. The labels indicate that for optimum results,
chlorflurenol ME can be used in conjunction with other traditional herbicides.
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B. Exposure Characterization
1. Environmental Fate and Transport Characterization
Environmental Persistence
The environmental persistence of chlorflurenol ME is difficult to determine with any certainty
due to the limited number of studies available, and the deficiencies within these studies.
However, based on these limited data, chlorflurenol ME appears to be highly to very highly
mobile in soil, and hydrolytically stable at pH 6. The study submitted by the registrant in order to
fulfill the aerobic soil metabolism data requirements was determined to be unacceptable because
the study was conducted outdoor. However, since this aerobic soil metabolism study could be
considered supplemental as a small-scale quasi field dissipation study, its results could be
interpreted qualitatively. Chlorflurenol ME appears to degrade rapidly under field conditions.
The primary route of dissipation could not be determined. Photodegradation may also occur;
however, no studies were submitted, so this degradation route could not be confirmed.
In buffered aqueous solutions, the half-life of chlorflurenol ME at pH 6 and pH 9 was 161.2 and
0.20 days, respectively. The phototransformation of chlorflurenol ME could not be evaluated
because no studies were submitted. In the registrant-claimed aerobic soil metabolism study
(which was considered by EFED as a small-scale quasi field dissipation study), chlorflurenol ME
degraded with a half-life of 1.3 days in a sandy loam soil from Germany. However, these
experimental plots were outdoors under uncontrolled environmental conditions, and without a
phototransformation study to reference, it is uncertain to what extent degradation occurred due to
microbial metabolism, and/or photodegradation. The metabolism of chlorflurenol ME under
aerobic aquatic, anaerobic soil, and anaerobic aquatic conditions, and the potential for
bioaccumulation could not be evaluated because no studies were submitted in these areas.
Expected Mobility
Chlorflurenol ME is highly to very highly mobile in sandy loam soil from Germany, with a KFoc
of 109. The field dissipation of chlorflurenol ME could not be evaluated because no studies were
submitted.
Environmental Metabolites
The major transformation product of chlorflurenol ME that was quantified was 2-chloro-9-
fluorenone (Compound IV; fluorenone). 2-Chloro-9-hydroxyfluorene-9-carboxylic acid
(Compound II) was also identified as a major transformation product of hydrolysis, but was not
quantified.
The transformation pathway of chlorflurenol ME in the environment is difficult to determine with
any certainty due to the limited number of studies available, and the deficiencies within these
studies.
2. Measures of Aquatic Exposure
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a. Aquatic Exposure Modeling
Since there are limited fate data for chlorflurenol ME no aquatic modeling was conducted.
b. Aquatic Exposure Monitoring (Field Data)
There are no aquatic exposure monitoring data.
3. Terrestrial Exposure Assessment
Terrestrial wildlife exposure estimates are typically calculated for birds and mammals,
emphasizing a dietary exposure route for uptake of pesticide active ingredients. These exposures
are considered as surrogates for terrestrial-phase amphibians as well as reptiles. For exposure to
terrestrial organisms, such as birds and small mammals, pesticide residues on food items are
estimated, based on the assumption that organisms are exposed to a single pesticide residue in a
given exposure scenario.
a. Terrestrial Animal Exposure Modeling
A primary concern with chlorflurenol ME is that birds and mammals may be exposed shortly
after application through oral or dietary exposure to vegetative plant material or insects when
foraging in the treated fields for nesting material or food. Therefore estimation of pesticide
concentrations in wildlife food items focuses on quantifying possible dietary ingestion of residues
on vegetative matter and insects. The EFED terrestrial exposure model T-REX (T-REX, Version
1.2.3, dated August 8, 2005) is used to estimate exposures and risks to avian and mammalian
species. Input values for avian and mammalian toxicity as well as chemical application and foliar
dissipation half-life data are required to run the model. The model provides estimates of exposure
concentrations and risk quotients (RQs). Specifically, the model provides estimates of
concentrations (upper-bound and mean) of chemical residues on the surface of different types of
foliage and insects that may be dietary sources of exposure to avian, mammalian, reptilian, or
terrestrial-phase amphibian receptors. The surface residue concentration (ppm) is estimated by
multiplying the application rate (pounds active ingredient per acre) by a value specific to each
food item. These values (termed the Hoerger-Kenaga estimates) along with a more detailed
discussion of the methodology implemented by T-REX, are presented in Appendix C (T-REX
Model).
For multiple applications, the EEC is determined by adding the mass on the surface immediately
following the application to the mass of the chemical still present on the surfaces on the day of
application (determined based on first order kinetics using the foliar dissipation half-life as the
rate constant). Input values used for estimating avian and mammalian exposure risks to
chlorflurenol ME are summarized in Table 4.
Table 4. Input parameters used in T-REX vl.2.3 to determine terrestrial EECs for the
maximum chlorflurenol ME spray application scenario.
Input Variable Parameter Value Source
Maximum application rate 3.0 Ib a.i./A Product Label
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Table 4. Input parameters used in T-REX vl.2.3 to determine terrestrial EECs for the
maximum chlorflurenol ME spray application scenario.
Input Variable Parameter Value Source
Likely # of applications per year 8 HED a
Likely application interval 28 days HED a
Foliar dissipation half-life 35 days T-REX Default Value
a HED used information provided on the labels along with their best professional judgment of the crop/weed growth cycles,
pest pressure timing, etc. to determine the application interval and yearly number of applications. EFED used the HED data
to maintain consistency between EFED and HED.
Uncertainties in the terrestrial EECs are associated with a lack of data on dissipation from foliar
surfaces. When data are absent, as in this case, EFED assumes a 35-day foliar dissipation half-
life, based on the work of Willis and McDowell (1987). In this respect, the EECs for
chlorflurenol ME may be an overestimation of actual concentrations if the half-life under field
conditions is lower than the default value. Because foliar dissipation data are not available, the
extent to which EECs may be overestimated or underestimated is uncertain.
In addition, EFED used a "likely" application interval and yearly application rate, since no
information was provided on the label. Risks could be underestimated if the actual application
rate, frequency of application, and/or number of applications are higher than the input parameters
used for the exposure scenario that was modeled. For this risk assessment, the T-REX model was
run for turf use with the maximum proposed application rate (3.0 Ib a.i./A), 8 applications/year
(derived by HED, see Appendix B), and a 28-day application interval (derived by HED, see
Appendix B), to assess risk to terrestrial organisms. HED used information provided on the
labels along with their best professional judgment of the crop/weed growth cycles, pest pressure
timing, etc. to determine the application interval and yearly number of applications. EFED used
the HED data to maintain consistency between EFED and HED.
By comparing estimated exposure concentrations to acute and chronic toxicity reference values,
RQs are calculated. The EECs on food items may be compared directly with dietary toxicity data
or converted to an oral dose, as is done for small mammals. For mammals, the residue
concentration is converted to daily oral dose based on the fraction of body weight consumed daily
as estimated through mammalian allometric relationships. The screening-level risk assessment
for chlorflurenol ME uses upper-bound predicted residues as the measure of exposure.
Summaries of the predicted upper-bound and mean residues of chlorflurenol ME that may be
expected to occur on selected avian or mammalian food items immediately following application
for the maximum use scenario are presented in Table 5.
For the maximum chlorflurenol ME application scenario, acute concentrations for different forage
types ranged from 104.22 to 1671.50 ppm for upper-bound residues and 48.75 to 591.99 ppm for
mean residues. Chlorflurenol ME concentrations were highest on the surfaces of short grass and
lowest on the surfaces of fruits, pods, and large insects.
Table 5. Upper-bound and mean terrestrial EECs estimated for the chlorflurenol ME
spray application scenario using Kenaga values.
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Forage Type
short grass
tall grass
broadleaf plants and small insects
fruits/pods/large insects
Upper-bound
Residues
(ppm)
1671.50
766.10
940.22
104.22
Mean Residues
(ppm)
591.99
250.72
313.41
48.75
b. Terrestrial Exposure Monitoring (Field Data)
No data were identified to provide information on terrestrial monitoring.
4. Non-Target Plant Exposure Assessment
No toxicity data were identified to provide information on terrestrial plants.
C. Ecological Effects Characterization
In screening-level ecological risk assessments, effects characterization describes the types of
effects a pesticide can produce in an aquatic or terrestrial organism. This characterization is
based on registrant-submitted studies that describe acute and chronic effects toxicity information
for various aquatic and terrestrial animals and plants. Appendix D summarizes the results of the
registrant-submitted toxicity studies used to characterize effects for this risk assessment. Toxicity
testing reported in this section does not represent all species of birds, mammals, or aquatic
organisms. Only a few surrogate species for both freshwater fish and birds are used to represent
all freshwater fish (2000+) and bird (680+) species in the United States. For mammals, acute
studies are usually limited to Norway rat or the house mouse. Estuarine/marine testing is usually
limited to a crustacean, a mollusc, and a fish. Also, neither reptiles nor amphibians are tested.
The risk assessment assumes that avian and reptilian toxicities are similar. The same assumption
is used for fish and aquatic amphibians.
In general, categories of acute toxicity ranging from "practically nontoxic" to "very highly toxic"
have been established for aquatic organisms (based on LC50 and EC50 values or limit of
solubility), mammals (based on LD50 values), avian species (based on LD50 and LC50 values), and
non-target insects (based on LD50 values for honey bees) (U.S. EPA 2001). These categories are
presented in Appendix D.
1. Aquatic Effects: Animals and Plants
No aquatic animal or plant toxicity studies are available for chlorflurenol ME. There were
several fish and aquatic invertebrate studies submitted; however they were considered
unacceptable due to major deviations from guidelines. Therefore, effects cannot be determined.
2. Terrestrial Effects
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The toxicity endpoints used to characterize risks of chlorflurenol ME exposure to birds and
mammals are summarized in Table 6. Results of all studies in terrestrial organisms are
summarized in Appendix D, Tables Dl to D3.
Table 6. Chlorflurenol ME Toxicity Reference Values for Terrestrial Organisms.
Exposure
Scenario
Species
Scientific
Name
Exposure
Duration
Toxicity
Reference
Value
Effects
Reference
(Classification)
Mammals
Acute
Chronic
Rat
Rat
Rattus
norvegicus
Rattus
norvegicus
Acute Oral
Days 6-1 5 of
gestation
LD50 > 5000
mg/kg body
weight
Maternal
NOAEL = 250
mg/kg/day
Developmental
NOAEL = 250
mg/kg/day
Mortality
body weight
gain decrement
and nominally
decreased food
efficiency
delayed
ossification in
skull bones
43355402
(Acceptable)
45190901
(Acceptable)
Birds
Acute
(Dose-
based)
Acute
(Dietary-
based)
Chronic
Bobwhite
Quail
Bobwhite
Quail
Mallard
Duck
Colinus
virginianus
Colinus
virginianus
Anas
Platyrhync
hos
Single Oral
Dose
8 days
LD50>10,000
mg a.i./kg body
weight
LC50 > 5,000 mg
a.i./kg diet
Mortality
Mortality
43595401
(Acceptable)
43623601
(Acceptable)
43623602
(Acceptable)
Data gap
Plants
Acute
Chronic
Data gap
Data gap
a. Terrestrial Animals
Mammalian Species
Results of an acute oral exposure study in laboratory rats (MRID 43355402; Acceptable) show
that the LD50 for chlorflurenol ME is >5,000 mg a.i./kg body weight; therefore, chlorflurenol ME
is categorized as practically nontoxic to mammalian species on an acute oral basis. EFED will
use the acute oral LD50 of >5,000 mg a.i./kg body weight to evaluate acute dose-based risk to
mammalian species.
In a developmental toxicity study (MRID 45190901), chlorfurenol-methyl ester was administered
to pregnant Sprague Dawley rats by gavage. The maternal NOAEL was 250 mg/kg bw/day. The
maternal LOAEL is 750 mg/kg bw/day based on body weight gain decrement and nominally
decreased food efficiency. The developmental NOAEL is 250 mg/kg bw/day. The developmental
LOAEL is 750 mg/kg bw/day, based on treatment-related delayed ossification in skull bones
[nasal and frontal] in fetuses and litters. In addition a cleft palate was seen in each of two litters
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and one diaphragmatic hernia at 1000 mg/kg bw/day and one cleft palate at 750 mg/kg bw/day
(cleft palate is rare in rats).
Avian Species
Results of an acute oral exposure study in bobwhite quail (MRID 43595401; Acceptable) indicate
that the LD50 for chlorflurenol ME is >10,000 mg a.i./kg body weight; therefore, chlorflurenol
ME is categorized as practically nontoxic to avian species on an acute oral basis. EFED will use
the acute oral LD50 of >10,000 mg a.i./kg body weight to evaluate acute dose-based risk to avian
species.
Results of subacute dietary studies in mallard ducks (MRID 43623602; Acceptable) and bobwhite
quail (MRID 43623601; Acceptable), show that the acute dietary LC50 value is >5,000 mg a.i./kg
diet, indicating that chlorflurenol ME is practically nontoxic on an acute dietary basis. EFED will
use the LC50 value of >5,000 mg a.i./kg diet to assess the risk of acute dietary exposure of birds to
chlorflurenol ME.
Non-target Insects
No data are available for non-target insects.
b. Terrestrial Plants
No data are available for terrestrial plants.
IV. Risk Characterization
Risk characterization is the integration of exposure and effects characterization to determine the
ecological risk from the use of chlorflurenol ME and the likelihood of effects on aquatic life,
wildlife, and plants based on varying pesticide-use scenarios. The risk characterization provides
an estimation and a description of the risk; articulates risk assessment assumptions, limitations,
and uncertainties; synthesizes an overall conclusion; and provides the risk managers with
information to make regulatory decisions.
A. Risk Estimation - Integration of Exposure and Effects Data
Results of the exposure modeling and toxicity effects data are used to evaluate the likelihood of
adverse ecological effects on non-target species. For the assessment of chlorflurenol ME risks,
the risk quotient (RQ) method is used to compare exposure and measured toxicity values (refer to
Appendix E). Estimated environmental concentrations (EECs) are divided by the most sensitive
acute and chronic toxicity values. The RQs are then compared to the Agency's levels of concern
(LOCs). These LOCs, summarized in Appendix E, are the Agency's interpretive policy and are
used to analyze potential risk to non-target organisms and the need to consider regulatory action.
These criteria are used to indicate when a pesticide's use as directed on the label has the potential
to cause adverse effects on non-target organisms. Details of all RQs are provided in Appendix F.
1. Non-target Aquatic Animals and Plants
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a. Acute and Chronic Risk to Animals
Acute and chronic risk to fish and invertebrates cannot be evaluated at this time because no
toxicity data are available. Risk cannot be precluded.
b. Aquatic Plants
Risk to aquatic plants cannot be evaluated at this time because no toxicity data are available.
Risk cannot be precluded.
2. Non-target Terrestrial Animals
a. Acute Risk to Birds and Mammals
Mammalian Species
Definitive acute dose-based RQ values for mammalian receptors could not be derived because all
treated animals survived and gained weight in the submitted acute oral toxicity study on
mammals (the oral LD50 was >5000 mg a.i./kg body weight). Based on these results,
chlorflurenol ME TGAI is categorized as practically non-toxic to mammals on an acute oral
basis.
Avian Species
Definitive acute dose- and dietary-based RQ values for avian receptors could not be derived
because the acute effects data show that chlorflurenol ME is practically non-toxic to birds (LD50
>10,000 mg a.i./kg bodyweight and LC50 > 5,000 mg a.i./kg diet).
b. Chronic Risk to Birds and Mammals
Mammalian Species
T-REX was used to calculate chronic RQs for mammals using the chronic toxicity value for the
rat (MRID 45190901). Dose- and dietary-based chronic RQs for mammals are summarized in
Table 7 (also in Table F-4 of Appendix F). Dose-based RQs exceed the chronic risk level (LOC
1) to mammalian species for 15-g and 35-g mammals that forage on short grass, tall grass, and
broadleaf plants/small insects (RQ range = 1.14 to 2.90) and for 1000-g mammals that forage on
short grass (RQ = 1.33). Dietary-based RQs do not exceed chronic risk (LOC 1) to mammalian
species (RQ range = 0.02 to 0.33). These RQs were calculated using upper-bound residues.
Table 7. Dose- and Dietary-based Chronic RQs for Mammals Exposed to Chlorflurenol ME
Based on Upper Bound Residues as Calculated bv T-REX.
Crop Use
(Application
Rate)
Body
Weigh
t(g)
Mammalian Risk Quotients
Short
Grass
Tall
Grass
Broadleaf
Plants/Small
Insects
Fruits/Pods/La
rge Insects
Seeds
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Table 7. Dose- and Dietary-based Chronic RQs for Mammals Exposed to Chlorflurenol ME
Based on Upper Bound Residues as Calculated by T-REX.
Crop Use
(Application
Rate)
Body
Weigh
t(g)
Mammalian Risk Quotients
Short
Grass
Tall
Grass
Broadleaf
Plants/Small
Insects
Fruits/Pods/La
rge Insects
Seeds
Dose-based Chronic Mammalian RQs a
Turf
(3.01ba.i./A)
15
35
1,000
2.90 c
2.48 c
1.33 c
1.33 c
1.14 c
0.61
1.63 c
1.39 c
0.75
0.18
0.15
0.08
0.04
0.03
0.02
Dietary-based Chronic Mammalian RQs b
Turf(3.01ba.i./A)
0.33
0.15
0.19
0.02
NA
a Chronic dose-based RQ = EEC/NO AEL, where EEC values are upper bound residues
expressed as equivalent dose (mg a.i./kg body weight) generated from T-REX and the toxicity
value is the chronic dose-based NO AEL = 250 mg a.i./kg/day in the rat.
b Chronic dietary -based RQ = EEC/NO AEC, where EEC values are upper bound residues
expressed as dietary concentrations (mg a.i./kg diet) generated from T-REX and the toxicity
value is the chronic dietary-based NOAEC = 5000 mg a.i./kg diet in rats (converted from the
rat oral dose study).
c RQs are above the LOC for chronic risk (LOC 1).
Avian Species
No toxicity data are available to quantitatively assess chronic risk of chlorflurenol ME exposure
to birds. Risk cannot be precluded.
c. Risk to Terrestrial Invertebrates
No toxicity data are available to quantitatively assess risk of chlorflurenol ME exposure to
terrestrial invertebrates. Risk cannot be precluded.
3. Non-target Terrestrial and Semi-Aquatic Plants
No toxicity data are available to quantitatively assess risk of chlorflurenol ME exposure to
terrestrial plants. However, since chlorflurenol ME is used as an herbicide and as a growth
regulator, risk to non-target plants may occur.
B. Risk Description - Interpretation of Direct Effects
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There are no data on the usage of chlorflurenol ME; however, the registrant suggests it is used in
low volumes. Therefore, even though RQs may indicate risk, exposure may be overestimated due
to the low volume applied yearly across the contiguous United States. RQs, and therefore risk,
may also be under- or over-estimated due to major uncertainties and gaps in the fate and toxicity
data (see section IV.C). In most instances RQs could not be calculated due to data gaps.
1. Risks to Aquatic Organisms
There are no acceptable toxicity studies and little environmental fate data to evaluate potential
exposure; therefore, EFED is unable to preclude risk to aquatic animals and plants.
Since chlorflurenol ME is applied as a spray to non-food crops that are ubiquitous (i.e. turf, rights
of ways, fence rows), a wide variety of non-target aquatic organisms may come into contact with
chlorflurenol ME and its degradates in runoff or spray drift. Based on limited fate data,
chlorflurenol ME may leach through the ground quickly decreasing the amount of chlorflurenol
ME available for runoff to surface water. However, this study was conducted on sandy loam soils
which do not occur throughout the U.S. In addition, this does not account for chlorflurenol ME
moving to aquatic systems via spray drift. This study was classified as supplemental due to
guideline deviations which increases the amount of uncertainty. Once in the water, the fate
cannot be determined. Therefore, if chlorflurenol ME enters water systems, non-target aquatic
organisms may be at risk.
2. Risks to Terrestrial Organisms
a. Acute Risk to Birds and Mammals
Based on the submitted acute oral toxicity studies on birds and mammals, chlorflurenol ME is
categorized as practically non-toxic to birds and mammals on an acute oral and/or dietary (birds
only) basis (LD50 > 10000 mg a.i./kg body weight for birds; LC50 > 5000 mg a.i./kg diet for birds;
LD50 > 5000 mg a.i./kg body weight for mammals). No effects were seen in the acute avian
studies; however, the mammal study showed rats with hunched posture, lethargy and diarrhea.
RQs could potentially exceed acute listed species LOCs unless the actual LD50 values are
established in laboratory studies to be greater than -16,715 mg a.i./kg body weight or if the
amount available in the environment was lowered below 500 ppm (see Appendix C on how to
calculate adjusted LD50 values, dose-based EECs, and acute dose-based RQs). Therefore, some
uncertainty concerning acute oral risk to birds and mammals as a result of exposure to
chlorflurenol ME does exist. In addition, the study testing oral toxicity to birds did not state
which components were included in the test material. EFED assumes the test material contained
all three components which may underestimate risk to birds on an acute oral basis.
b. Chronic Risk to Birds and Mammals
Relative to the use patterns identified in this assessment, exposure of chlorflurenol ME spray
application is expected to result in chronic risk to listed and non-listed mammals. As shown in
Table 7, some dose-based RQs for chronic risk to mammalian species are above the chronic risk
LOG (1) for the maximum spray application scenario considered in this risk assessment (RQ
range = 0.02 to 2.90). Specifically, chronic dose-based RQs exceed the LOC for mammals
feeding on short grass (RQ range = 1.33 to 2.90), tall grass (RQ range = 0.61 to 1.33), and
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broadleaf plants/small insects (RQ range = 0.75 to 1.63). The chronic LOG is not exceeded for
mammals of any size feeding on fruits/pods/large insects (RQ range = 0.08 to 0.18) or seeds (RQ
range = 0.02 to 0.04). Chronic dietary-based RQs do not exceed the chronic LOC for mammals
(RQ range = 0.02 to 0.33).
To bound the estimates of risk to mammals resulting from chronic exposure to chlorflurenol ME,
RQs using mean Kenaga residue values in addition to upper-bound values were calculated (See
Table F-5;Appendix F). Using the non-conservative mean residue values, implying that higher
predicted residue values are expected half the time, only the RQ for 15g mammals that feed on
short grass (RQ = 1.02) exceeds the chronic LOC.
These RQs are based on a developmental study that shows evidence of delayed skull ossification
and cleft palates in young rats. These endpoints are not adequate for determining risk to the
survival and fecundity of a population. However, without other studies EFED used these data.
Therefore, the RQs may not accurately portray chronic risk to mammals. Risk may be under- or
over-estimated.
There are uncertainties associated with the RQ values derived with T-REX. In the absence of
foliar dissipation half-life data, application interval, and number of yearly applications, the
default half-life and "likely" interval and yearly applications were used, which may have
overestimated or underestimated the risk to terrestrial species.
The dose-based approach considers the uptake and absorption kinetics of a gavage toxicity study
to approximate exposure associated with uptake from a dietary matrix. Toxic response is a
function of duration and intensity of exposure. For many compounds a gavage dose represents a
very short-term high intensity exposure. Although the dose-based estimates may not reflect
reality in that animals do not receive a gavage while feeding, it is possible that a short-duration,
high-intensity exposure could occur associated with feeding on an agricultural field since many
birds may gorge themselves when food items are available. While the dietary-based estimates
may suggest greater "realism," they too suffer from some uncertainties. Primarily, the dietary-
based approach assumes that animals in the field are consuming food at a rate similar to that of
confined laboratory animals despite the fact that energy content in food items differs between the
field and the laboratory as does the energy requirements of wild and captive animals.
No quantitative data are available to characterize chronic risks from application of chlorflurenol
ME to birds; therefore, EFED cannot preclude chronic risk to birds.
c. Non-target Terrestrial Invertebrates
No quantitative data are available to characterize risks from application of chlorflurenol ME to
terrestrial invertebrates. Since chlorflurenol ME is applied in areas where there may be
pollinators and other invertebrates, EFED cannot preclude risk to terrestrial invertebrates.
d. Terrestrial Plants
No quantitative data from guideline studies are available to characterize risks from application of
chlorflurenol ME to terrestrial plants. However, since chlorflurenol ME is used as an herbicide
and growth regulator, risk to terrestrial plants is assumed.
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Chlorflurenol ME has been shown to induce parthenocarpy in cucumbers (Robinson et al. 1971)
and interrupt ovule development in muskmelons (Snyder et al. 1983). Robinson et al. (1971)
stated that at lower concentrations (10-20 ppm), parthenocarpy was induced when cucumber
plants were treated in the flowering stage; however, at a higher concentration (40 ppm)
parthenocarpy was induced two week prior to the flowering stage. In muskmelons, ovule
development was halted when chlorflurenol was applied 10-12 days before anthesis (Snyder et
al. 1983). Since parthenocarpic plants produce fruits with no seeds, sexual reproduction cannot
occur. Nontarget plants that come in contact with chlorflurenol ME may also suffer from
increased parthenocarpy, severely limiting their ability to reproduce.
3. Review of Incident Data
Incident reports submitted to EPA since approximately 1994 have been tracked by assignment of
"incident numbers" in an Incident Data System (IDS), microfiched, and then entered into a
second database, the Ecological Incident Information System (EIIS). An effort has also been
made to enter information to EIIS on incident reports received prior to establishment of current
databases. Incident reports are not received in a consistent format (e.g., states and various labs
usually have their own formats), may involve multiple incidents involving multiple chemicals in
one report, and may report only part of a given incident investigation (e.g., residues). While
some progress has been made in recent years in getting incident reports submitted and entered,
there has never been the level of resources assigned to incidents that there has been assigned to
the tracking and review of laboratory toxicity studies, for example.
No incident reports involving aquatic or terrestrial exposure to chlorflurenol ME have been
reported.
4. Endocrine Effects
Under the Federal Food, Drug and Cosmetic Act (FFDCA), as amended by the Food Quality
Protection Act (FQPA), EPA is required 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 was scientific basis for including, as part of the program, the 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. For
pesticide chemicals, EPA will use FIFRA, to the extent that effects in wildlife may help
determine whether a substance may have an effect in humans, and the FFDCA authority to
require the wildlife evaluations. As the science develops and the resources allow, screening of
additional hormone systems may be added to the Endocrine Disrupter Screening Program
(EDSP). When the appropriate screening and or testing protocols being considered under the
Agency's Endocrine Disrupter Screening Program have been developed, chlorflurenol ME may
be subjected to additional screening and or testing to better characterize effects related to
endocrine disruption.
Results of the submitted developmental study in mammals show exposure to chlorflurenol ME
produces adverse effects on reproductive parameters. Observed effects in the submitted
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mammalian study include maternal body weight gain decrement and nominally decreased food
efficiency, as well as treatment related delayed ossification in skull bones (nasal and frontal) in
fetuses and litters. Results of this developmental study suggest that chlorflurenol ME could be a
candidate for additional screening and/or testing to better characterize effects related to endocrine
disruption.
Chronic exposure studies on the effects of chlorflurenol have not been conducted in aquatic
organisms or birds. Therefore, EFED must consider the possibility that chlorflurenol ME may
have detrimental effects on the endocrine system in these taxa.
5. Threatened and Endangered Species Concerns
a. Action Area
For listed species assessment purposes, the action area is considered to be the area affected
directly or indirectly by the Federal action and not merely the immediate area involved in the
action. At the initial screening-level, the risk assessment considers broadly described taxonomic
groups and so conservatively assumes that listed species within those broad groups are collocated
with the pesticide treatment area. This means that terrestrial plants and wildlife are assumed to be
located on or adjacent to the treated site and aquatic organisms are assumed to be located in a
surface water body adjacent to the treated site. The assessment also assumes that the listed
species are located within an assumed area which has the relatively highest potential exposure to
the pesticide, and that exposures are likely to decrease with distance from the treatment area.
Section III(A) of this risk assessment presents the pesticide use sites that are used to establish
initial collocation of species with treatment areas.
If the assumptions associated with the screening-level action area result in RQs that are below the
listed species LOCs, a "no effect" conclusion is made with respect to listed species in that taxa,
and no further refinement of the action area is necessary. Furthermore, RQs below the listed
species LOCs for a given taxonomic group indicate no concern for indirect effects upon listed
species that depend upon the taxonomic group covered by the RQ as a resource. However, in
situations where the screening assumptions lead to RQs in excess of the listed species LOCs for a
given taxonomic group, a potential for a "may affect" conclusion exists and may be associated
with direct effects on listed species belonging to that taxonomic group or may extend to indirect
effects upon listed species that depend upon that taxonomic group as a resource. In such cases,
additional information on the biology of listed species, the locations of these species, and the
locations of use sites could be considered to determine the extent to which screening assumptions
regarding an action area apply to a particular listed organism. These subsequent refinement steps
could consider how this information would impact the action area for a particular listed organism
and may potentially include areas of exposure that are downwind and downstream of the pesticide
use site.
b. Taxonomic Groups Potentially at Risk
The Level I screening assessment process for listed species uses the generic taxonomic group-
based process to make inferences on direct effect concerns for listed species. The first iteration of
reporting the results of the Level I screening is a listing of pesticide use sites and taxonomic
groups for which RQ calculations reveal values that meet or exceed the listed species LOCs. In
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the majority of cases, the screening-level risk assessment process reports RQ calculations for the
following broad taxonomic groupings:
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• Birds (also used as surrogate for terrestrial-phase amphibians and reptiles)
• Mammals
• Freshwater fish (also used as a surrogate for aquatic phase amphibians)
• Freshwater invertebrates
• Estuarine/marine fish
• Estuarine/marine invertebrates
• Terrestrial plants
• Algae and aquatic plants
i. Discussion of Risk Quotients
Should estimated exposure levels occur in proximity to listed resources, the available screening-level information suggests a potential concern for
direct effects to listed fish (freshwater and estuarine/marine), aquatic invertebrate (freshwater and estuarine/marine), beneficial insect, avian, reptile,
amphibian, and mammalian species associated with areas where chlorflurenol ME is used. More specifically, the available screening-level
information indicates the following:
Fish and Aquatic Invertebrates
Risk quotients for acute and chronic effects to freshwater and estuarine/marine fish and invertebrates could not be calculated because there are no
acceptable toxicity studies.
Aquatic Plants and Algae
Risk quotients for aquatic plants and algae could not be calculated because there are no acceptable toxicity studies.
Birds
Definitive acute dose- or dietary-based RQ values for avian receptors could not be derived because there are no definitive LD50 or LC50 values.
Risk quotients for chronic effects to birds could not be calculated because there are no acceptable toxicity studies.
Mammals
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Definitive acute dose- or dietary-based RQ values for mammalian receptors could not be derived because there are no definitive LD50 or LC50 values.
The use of chlorflurenol ME under the maximum application rate scenarios results in dose-based RQs for mammals exceeding the chronic risk LOG
(1) for exposure via short grass, tall grass, and broadleaf plants/small insects.
Terrestrial Plants
Risk quotients for terrestrial plants could not be calculated because there are no acceptable toxicity studies.
ii. Probit Dose Response Relationship
The probit slope response relationship is evaluated to calculate the chance of an individual event corresponding to the listed species acute LOCs. The
analysis uses the EFED spreadsheet lECvl. 1 .xls, developed by Ed Odenkirchen (6/22/04). It is important to note that the IEC model output can go as
low as 1 x 10~16 in estimating the event probability. This cut-off is a limit in the Excel spreadsheet environment and is not to be interpreted as an agreed
upon lower bound threshold for concern for individual effects in any given listed species.
If an LD50 or LC50 has been established for a particular taxonomic group, but information is unavailable to estimate a slope from a study, a default
slope assumption of 4.5 is used as per original Agency assumptions of typical slope cited in Urban and Cook (1986). In instances where an LC50 or
LD50 has not been established for a particular taxonomic group, an individual effects probability is not estimated.
Freshwater and Estuarine/Marine Fish and Invertebrates
No toxicity data are available to quantitatively assess individual risk of chlorflurenol ME exposure to aquatic organisms.
Mammals and Birds
Definitive LC5o/LD5oS are not available to quantitatively assess individual risk of chlorflurenol ME exposure to terrestrial organisms.
c. Indirect Effects Analysis
The Agency acknowledges that pesticides have the potential to exert indirect effects upon the listed organisms by, for example, perturbing forage or
prey availability, altering the extent of nesting habitat, and creating gaps in the food chain. In conducting a screen for indirect effects, direct effect
LOCs for each taxonomic group are used to make inferences concerning the potential for indirect effects upon listed species that rely upon non-listed
organisms in these taxonomic groups as resources critical to their life cycle. Species-specific concerns for chlorflurenol ME indirect effects to listed
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organisms will require a determination of the coincidence of chlorflurenol ME use with locations of listed species and the biologically based resources
upon which they depend.
The Agency uses the dose response relationship from the toxicity study used for calculating the RQ to estimate the probability of acute effects
associated with an exposure equivalent to the EEC (see Probit Dose response Relationship above). In instances where information on the dose
response is available, it serves as a guide to establish the need for and extent of additional analysis that may be performed using Services-provided
"species profiles" as well as evaluations of the geographical and temporal nature of the exposure to ascertain if a "not likely to adversely affect"
determination can be made. The degree to which additional analyses are performed is commensurate with the predicted probability of adverse effects
from the comparison of the dose response information with the EECs. The greater the probability that exposures will produce effects on a taxa, the
greater the concern for potential indirect effects for listed species dependant upon that taxa, and therefore, the more intensive the analysis on the
potential listed species of concern, their locations relative to the use site, and information regarding the use scenario (e.g., timing, frequency, and
geographical extent of pesticide application).
Relative to chlorflurenol ME proposed usage, EFED's screening level analysis shows that there is a concern for indirect effects to listed species that
may depend upon other taxonomic group for their survival (e.g., invertebrates as a food source for listed fish, etc.). Screening-level RQs for avian
species potentially exceed the acute risk LOG and RQs for mammalian species exceed the acute and chronic risk LOG. Therefore, the nature of the
toxicological endpoint, Services-provided "species profiles," and further evaluation of the geographical and temporal nature of the exposure will need
to be considered to determine if a rationale for a "not likely to adversely affect" determination is possible. Using our best professional judgment,
EFED concludes that due to the lack of toxicity data for fish, aquatic invertebrates, aquatic plants, birds (chronic), and terrestrial plants, risk cannot be
precluded and there may be a potential concern for indirect effects to the following groups of organisms in the action area:
• Terrestrial plants
• Aquatic plants
• Birds
• Mammals
• Reptiles
• Aquatic Invertebrates
• Fish
• Amphibians
• Terrestrial Insects
For listed species that may potentially be indirectly affected by the Federal action, see Appendix G (Locates run).
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d. Critical Habitat
In the evaluation of pesticide effects on designated critical habitat, consideration is given to the physical and biological features (constituent elements)
of a critical habitat identified by the U.S. Fish and Wildlife and National Marine Fisheries Services as essential to the conservation of a listed species
and which may require special management considerations or protection. The evaluation of impacts for a screening-level pesticide risk assessment
focuses on the biological features that are constituent elements and is accomplished using the screening-level taxonomic analysis (risk quotients, RQs)
and listed species levels of concern (LOCs) that are used to evaluate direct and indirect effects to listed organisms.
The screening-level risk assessment has identified potential concerns for indirect effects on listed species for those organisms dependent upon aquatic
fish and invertebrates (including benthic animals), birds, reptiles, and mammals. In light of the potential for indirect effects, the next step for EPA and
the Service(s) is to identify which listed species and critical habitat are potentially implicated. Analytically, the identification of such species and
critical habitat can occur in either of two ways. First, the agencies could determine whether the action area overlaps critical habitat or the occupied
range of any listed species. If so, EPA would examine whether the pesticide's potential impacts on non-listed species would affect the listed species
indirectly, or directly affect a constituent element of the critical habitat. Alternatively, the agencies could determine which listed species depend on
biological resources, or have constituent elements that fall into the taxa that may be directly or indirectly impacted by the pesticide. Then EPA would
determine whether use of the pesticide overlaps the critical habitat or the occupied range of those listed species. At present, the information reviewed
by EPA does not permit use of either analytical approach to make a definitive identification of species that are potentially impacted indirectly or
critical habitats that is potentially impacted directly by the use of the pesticide. EPA and the Service(s) are working together to conduct the necessary
analysis.
This screening-level risk assessment for critical habitat provides a listing of potential biological features that, if they are constituent elements of one or
more critical habitats, would be of potential concern. These correspond to the taxa identified above as being of potential concern for indirect effects
and include the following: terrestrial plants, aquatic plants, reptiles, birds, mammals, fish and aquatic invertebrates, terrestrial insects, and amphibians.
This list should serve as an initial step in problem formulation for further assessment of critical habitat impacts outlined above, should additional work
be necessary.
Table 8 provides a list of the taxa that may be directly or indirectly affected.
Table 8. Listed species risks associated with direct or indirect effects due to applications
of chlorflurenol for turf use.
Listed Taxon
Direct Effects
Indirect Effects
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Terrestrial and semi-aquatic plants -
monocots
Terrestrial and semi-aquatic plants -
dicots
Insects
Birds
Terrestrial phase amphibians
Reptiles
Mammals
Aquatic vascular plants
Freshwater fish
Aquatic phase amphibians
Freshwater crustaceans
Mollusks
Marine/estuarine fish
Marine/estuarine crustaceans
Yes"
Yesa
Yesa
Acute - Yes c; Chronic - Yes "
Yesa
Acute - Yes c; Chronic - yes "
Acute - Yes c; Chronic - Yes b
Yesa
Yesa
Yesa
Yesa
Yesa
Yesa
Yesa
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
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a We cannot preclude risk due to lack of data.
b The reported RQ values are above the chronic LOG (1.0) for species that feed on short grass, tall grass, and broadleaf
plants/small insects (RQ range = 0.02 to 2.90).
cRQs could potentially exceed acute listed species LOCs unless the actual LD50 values are established in laboratory
studies to be greater than -16,715 mg a.i./kg body weight or if the amount available in the environment was lowered
below 500 ppm
e. Co-occurrence Analysis
The goal of the analysis for co-location is to determine whether sites of pesticide use are geographically associated with known locations of listed
species. At the screening level, this analysis is accomplished using the LOCATES database. The database uses location information for listed species
at the county level and compares it to agricultural census data for crop production at the same county level of resolution. The product is a listing of
federally listed species that are located within counties known to produce the crop upon which the pesticide will be used. Because the Level I
screening assessment considers both direct and indirect effects across generic taxonomic groupings, it is not possible to exclude any taxonomic
group from a LOCATES database run for a screening risk assessment. Given the extent of potential chlorflurenol ME usage across the U.S. and the
expected large number of listed species that are likely to occur in counties where chlorflurenol ME is used, a list of endangered/threatened species and
crop acreage at the county level for the taxonomic groups and crops of concern is not included in this phase of the risk assessment process.
Given that the potential extent of chlorflurenol ME usage includes every state, and that all taxonomic groups are included in the initial LOCATES run
for a screening-level risk assessment, Appendix G provides the entire list of endangered/threatened species at the state level. The registrant must
provide information on the proximity of federally listed birds, fish, mammals, amphibians, crustaceans, reptiles, arachnids, insects, plants, snails, and
clams to the chlorflurenol ME use sites. This requirement may be satisfied in one of three ways: 1) having membership in the FIFRA Endangered
Species Task Force (Pesticide Registration [PR] Notice 2000-2); 2) citing FIFRA Endangered Species Task Force data; or 3) independently producing
these data, provided the information is of sufficient quality to meet FIFRA requirements. The information will be used by the OPP Endangered
Species Protection Program to develop recommendations to avoid adverse effects to listed species.
C. Description of Assumptions, Limitations, Uncertainties, Strengths and Data Gaps
This risk assessment relies on best available estimates of environmental fate and physicochemical properties, maximum application rate of
chlorflurenol ME, maximum number of applications, and the shortest interval between applications. However, several uncertainties and model
limitations are noted and should be considered in interpreting the results of this risk assessment.
1. Assumptions, Limitations, Uncertainties, Strengths and Data Gaps Related to Exposure For All Taxa
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There are a number of areas of uncertainty in the aquatic and terrestrial risk assessments. There are no valid toxicity data for any aquatic species, birds
(chronic only), terrestrial invertebrates, and plants. The toxicity assessment for terrestrial animals is limited by the number of species tested in the
available toxicity studies. Use of toxicity data on representative species does not provide information on the potential variability in susceptibility to
acute and chronic exposures.
2. Assumptions, Limitations, Uncertainties, Strengths and Data Gaps Related to Exposure For Aquatic Species
The registrant has submitted three studies to support the environmental fate data requirements; however, these studies were considered either
supplemental or unacceptable (see reasons below). As a result, the uncertainty analysis could not be performed with confidence.
Guideline 161-1: The study was conducted at pHs 3, 6 and 9 rather than pHs 5, 7 and 9 as required in Subdivision N Guidelines. This study was
determined to be supplemental. The hydrolysis data requirements have not been fulfilled. A new study including pH 7 is required.
Guideline 162-1: The study was conducted outdoors in the summer where the environmental conditions, soil aerobicity, microbial viability, and soil
moisture were neither controlled nor reported. Subdivision N Guidelines require that the study be conducted in the dark at 25 ± 1°C. This study was
determined to be unacceptable. The aerobic soil metabolism data requirements have not been fulfilled. A new study using four soils is required.
Guideline 163-1: Only one test soil type was used in the adsorption study and it could not be determined if this German soil was comparable to soils
found in typical use areas in the United States. Subdivision N guidelines specify that four different soil types should be used. This study was
determined to be supplemental. The adsorption/desorption data requirements have not been fulfilled. A new study including three soils is required.
3. Assumptions, Limitations, Uncertainties, Strengths and Data Gaps Related to Exposure For Terrestrial Species
The dataset available to support the terrestrial exposure assessment for chlorflurenol ME is substantially incomplete. Application interval, number of
applications per year, and a foliar dissipation study, which are input variables for modeling of risks to birds and mammals (i.e., T-REX), are lacking.
The terrestrial modeling for chlorflurenol ME was conducted using "likely" application intervals and yearly applications, as derived by HED. Also a
default foliar dissipation half-life value of 35 days, based on the work of Willis and McDowell (1987), was used. Therefore, if these values are lower
or higher terrestrial EECs may be overestimated or underestimated.
a. Location of Wildlife Species
For screening terrestrial risk assessments, a generic bird or mammal is assumed to occupy either the treated field or adjacent areas receiving the
pesticide at a rate commensurate with the treatment rate on the target field. This assumption may lead to an overestimation of exposure to species that
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do not occupy the treated field. The actual habitat requirements of any particular terrestrial species are not considered, and it is assumed that species
occupy, exclusively and permanently, the treated area being modeled. This assumption leads to a maximum level of exposure in the risk assessment.
b. Routes of Exposure
Screening-level risk assessments for spray applications of pesticides consider dietary exposure alone, and assume that 100% of the diet is relegated to
single food types foraged only from treated fields. These assumptions are likely to be conservative for many species and will tend to overestimate
potential risks. The assumption of 100% diet from a treated area may be realistic for acute exposures, but long-term exposures modeled as single food
types composed entirely of material from a treated field is uncertain. Other routes of exposure, not considered in this assessment, are discussed below.
Incidental Soil Ingestion Exposure
This risk assessment does not consider incidental soil ingestion. Available data suggest that up to 15% of the diet can consist of incidentally ingested
soil depending on the species and feeding strategy (Beyer et al. 1994). A simple first approximation of soil concentration of pesticide from spray
application shows that ingestion of soil at an incidental rate of up to 15% of the diet would not increase dietary exposure.
Inhalation Exposure
The screening risk assessment does not consider inhalation exposure. Such exposure may occur through three potential sources: (1) spray material in
droplet form at the time of application (2) vapor phase pesticide volatilizing from treated surfaces, and (3) airborne particulate (soil, vegetative
material, and pesticide dusts).
Available data suggest that inhalation exposure at the time of application is not an appreciable route of exposure for birds. According to research on
mallards and bobwhite quail, respirable particle size in birds (particles reaching the lung) is limited to a maximum diameter of 2 to 5 microns.
Theoretically, inhalation of pesticide active ingredient in the vapor phase may be another source of exposure for some pesticides under some exposure
situations.
The impact from exposure to dusts contaminated with the pesticide cannot be assessed generically as partitioning issues related to application site soils
and chemical properties render the exposure potential from this route highly situation-specific.
Dermal Exposure
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The screening assessment does not consider dermal exposure, except as it is indirectly included in calculations of RQs based on lethal doses per unit of
pesticide treated area. Dermal exposure may occur through three potential sources: (1) direct application of spray to terrestrial wildlife in the treated
area or within the drift footprint, (2) incidental contact with contaminated vegetation, or (3) contact with contaminated water or soil.
The available measured data related to wildlife dermal contact with pesticides are extremely limited. The Agency is actively pursuing modeling
techniques to account for dermal exposure via direct application of spray and by incidental contact with vegetation.
Drinking Water Exposure
Drinking water exposure to a pesticide active ingredient may be the result of consumption of surface water or consumption of the pesticide in dew or
other water on the surfaces of treated vegetation. For pesticide active ingredients with a potential to dissolve in runoff, puddles on the treated field
may contain the chemical.
c. Incidental Pesticide Releases Associated with Use
This risk assessment is based on the assumption that the entire treatment area is subject to chlorflurenol ME application at the rates specified on the
label. In reality, there is the potential for uneven application of chlorflurenol ME through such plausible incidents as changes in calibration of
application equipment, spillage, and localized releases at specific areas of the treated field that are associated with specifics of the type of application
equipment used (e.g., increased application at turnabouts when using older ground application equipment).
d. Residue Levels Selection
As discussed earlier in the exposure section of this document, the Agency relies on the work of Hoerger and Kenaga (1972) and Fletcher et al. (1994)
for setting the assumed pesticide residues in wildlife dietary items. The Agency believes that these residue assumptions reflect a realistic upper-bound
residue estimate, although the degree to which this assumption reflects a specific percentile estimate is difficult to quantify. It is important to note that
the field measurement efforts used to develop the Fletcher estimates of exposure involve highly varied sampling techniques. It is entirely possible that
much of these data reflect residues averaged over entire above ground plants in the case of grass and forage sampling. Depending upon a specific
wildlife species' foraging habits, whole aboveground plant samples may either underestimate or overestimate actual exposure.
e. Dietary Intake - The Differences Between Laboratory and Field Conditions
The acute and chronic characterization of risk rely on comparisons of wildlife dietary residues with LC50 or NOAEC values expressed in
concentrations of pesticides in laboratory feed. These comparisons assume that ingestion of food items in the field occurs at rates commensurate with
those in the laboratory. Although the screening assessment process adjusts dry-weight estimates of food intake to reflect the increased mass in fresh-
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weight wildlife food intake estimates, it does not allow for gross energy and assimilative efficiency differences between wildlife food items and
laboratory feed.
On gross energy content alone, direct comparison of a laboratory dietary concentration- based effects threshold to a fresh-weight pesticide residue
estimate would result in an underestimation of field exposure by food consumption by a factor of 1.25 - 2.5 for most food items. Only for seeds would
the direct comparison of dietary threshold to residue estimate lead to an overestimate of exposure.
Differences in assimilative efficiency between laboratory and wild diets suggest that current screening assessment methods do not account for a
potentially important aspect of food requirements. Depending upon species and dietary matrix, bird assimilation of wild diet energy ranges from 23 -
80%, and mammal's assimilation ranges from 41 - 85% (U.S. Environmental Protection Agency, 1993). If it is assumed that laboratory chow is
formulated to maximize assimilative efficiency (e.g., a value of 85%), a potential for underestimation of exposure may exist by assuming that
consumption of food in the wild is comparable with consumption during laboratory testing. In the screening process, exposure may be underestimated
because metabolic rates are not related to food consumption.
Finally, the screening procedure does not account for situations where the feeding rate may be above or below requirements to meet free living
metabolic requirements. Gorging behavior is a possibility under some specific wildlife scenarios (e.g., bird migration) where the food intake rate may
be greatly increased. Kirkwood (1983) has suggested that an upper-bound limit to this behavior might be the typical intake rate multiplied by a factor
of 5.
In contrast, there is the potential for avoidance, operationally defined as animals responding to the presence of noxious chemicals in their food by
reducing consumption of treated dietary elements. This response is seen in nature where herbivores avoid plant secondary compounds. However,
reduced food intake, particularly over an extended period, could result in reduced survival or reproductive output.
4. Assumptions, Limitations, Uncertainties, Strengths and Data Gaps Related to Effects Assessment
The dataset available to support the terrestrial and aquatic effects assessment for chlorflurenol ME is incomplete. Data gaps, uncertainties, and
limitations are summarized as follows:
• Guidelines 72-1, 72-2, 72-3, 72-4: Acute and chronic data for freshwater and estuarine/marine fish and invertebrates are not available;
therefore, risk could not be assessed.
• Guideline 71-4: Avian reproduction studies are not available; therefore, risk could not be assessed.
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• Guideline 123-1, 123-2: Terrestrial plant seedling emergence and vegetative vigor studies are not available. In addition, aquatic plant growth
studies are not available; therefore risk could not be assessed. Since chlorflurenol ME is used as an herbicide and growth regulator, toxicity
data on non-target plants are necessary to estimate risk.
• Guideline 141-1: Data for honey bee acute contact toxicity are not available; therefore, risk could not be assessed.
• Acute oral and dietary toxicity studies in birds and acute oral toxicity studies in mammals failed to establish definitive acute LD5o/LC5o values
(i.e., the LC50 was expressed as "greater than" the highest dietary concentration tested); thus, acute RQ could not be calculated.
• The study testing oral toxicity to birds did not state which components were included in the test material. EFED assumes the test material
contained all three components which may underestimate risk to birds on an acute oral basis if in fact the test material only contained one of
the three components.
• The mammalian chronic RQs are based on a developmental study that shows evidence of delayed skull ossification and cleft palates in young
rats. These endpoints are not adequate for determining risk to the survival and fecundity of a population. However, without other studies
EFED used these data. Therefore, the RQs may not accurately portray chronic risk to mammals. Risk may be under- or over-estimated.
• Application interval and number of applications per year are not indicated on the label. For multiple application scenarios the T-REX model
requires both of these parameters in order to estimate exposure to terrestrial organisms. In the absence of these numbers an application
interval of 28 days and 8 applications per year were used as derived by HED (Appendix B). HED used information provided on the labels
along with best professional judgment of the crop/weed growth cycles, pest pressure timing, etc. to determine the application interval and
yearly number of applications. EFED used the HED data to maintain consistency between EFED and HED. Since these numbers are
considered "likely" applications per year, risk to terrestrial organisms may be underestimated.
a. Age Class and Sensitivity of Effects Thresholds
It is generally recognized that test organism age may have a significant impact on the observed sensitivity to a toxicant. The screening risk assessment
acute toxicity data for fish are collected on juvenile fish between 0.1 and 5 grams. Aquatic invertebrate acute testing is performed on recommended
immature age classes (e.g., first instar for daphnids, second instar for amphipods, stoneflies and mayflies, and third instar for midges). Similarly, acute
dietary testing with birds is also performed on juveniles, with mallard being 5-10 days old and quail at 10-14 days of age.
Testing of juveniles may overestimate the toxicity of direct acting pesticides in adults. As juvenile organisms do not have fully developed metabolic
systems, they may not possess the ability to transform and detoxify xenobiotics equivalent to the older/adult organism. The screening risk assessment
has no current provisions for a generally applied method that accounts for this uncertainty. In so far as the available toxicity data may provide ranges
of sensitivity information with respect to age class, the risk assessment uses the most sensitive life-stage information as the conservative screening
endpoint.
b. Lack of Effects Data for Amphibians and Reptiles
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Currently, toxicity studies on amphibians and reptiles are not required for pesticide registration. Since these data are lacking, the Agency uses fish as
surrogates for aquatic phase amphibians and birds as surrogates for terrestrial phase amphibians and reptiles. These surrogates are thought to be
reflective of or protective (more sensitive) of herpetofauna. Amphibians are characterized by a permeable skin. The most important route of exposure
for aquatic amphibians would likely be the dermal route. Using freshwater fish may be suitable surrogates since exposure would likely be surface area
dependent and the gill surface of many fish is a fairly large surface area. Also, both fish and amphibians are ectothermic so metabolic rates and
demands would likely be similar. For terrestrial species, however, the difference between amphibians and birds and reptiles and birds is quite large.
Terrestrial amphibians and reptiles are both ectothermic while birds are endothermic; birds have a higher basal metabolic rate required to maintain
constant body temperature. The higher metabolic demands of birds may be predispose birds to higher relative exposures. However, this does not
address any potential differences in toxicity. To date, there are few controlled studies on reptile species that could be used to compare to similar
studies on birds. A priori, there is no strong reason to think that one taxon is more or less sensitive than another. Therefore, it was assumed that the
use of surrogate effects data is sufficiently conservative to apply the broad of species within taxonomic groups. If other species are more or less
sensitive to chlorflurenol ME than the surrogates, risks may be under- or overestimated, respectively. The Agency is not limited to a base set of
surrogate toxicity information in establishing risk assessment conclusions. The Agency also considers toxicity data on non-standard test species when
available. Further research is required to determine whether, in general, reptiles and terrestrial-phase amphibians are suitably represented by bird
species in assessing risks for chlorflurenol ME.
c. Use of the Most Sensitive Species Tested
Although the screening risk assessment relies on a selected toxicity endpoint from the most sensitive species tested, it does not necessarily mean that
the selected toxicity endpoints reflect sensitivity of the most sensitive species existing in a given environment. The relative position of the most
sensitive species tested in the distribution of all possible species is a function of the overall variability among species to a particular chemical. The
relationship between the sensitivity of the most sensitive tested species versus wild species (including listed species) is unknown and a source of
significant uncertainty. In addition, in the case of listed species, there is uncertainty regarding the relationship of the listed species' sensitivity and the
most sensitive species tested.
The use of laboratory species has historically been driven by availability and ease of maintenance. A widespread comparison of species is lacking,
however, even variation within a species can be quite high. For example, in this assessment, acute studies on honey bees yielded different values.
5. Assumptions, Limitations, Uncertainties, Strengths and Data Gaps Related to the Acute and Chronic LOCs
The risk characterization section of the assessment document includes an evaluation of the potential for individual effects to listed species at an
exposure level equivalent to the LOC. This evaluation is based on the median lethal dose estimate and dose/response relationship established for the
effects study corresponding to each taxonomic group for which the LOCs are exceeded. The slope of the probit-dose response is used to generate a
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probability of individual effects near the low end tail of the curve. Predictions based on low probability events are by nature highly uncertain.
Moreover, for this assessment the dose-response curve representing a given taxon is generated from one study using one species. It is likely that the
resulting dose-response relationship does not represent the response of all species within a taxon. Calculating the probability of individual effects at
the lower and upper bounds of the slope is designed to address this source of uncertainty but the extent to which this captures the variability within a
taxon is unknown. In some cases, a probit dose-response relationship cannot be calculated. In these instances, event probabilities are calculated based
on a default slope assumption of 4.5 with upper and lower confidence intervals of 2 and 9 (Urban and Cook, 1986).
V. Literature Cited
Environmental Fate MRID Studies Submitted to EPA
MRID 43496201
MRID 43496202b
MRID 43496202a
MRID 43595403
Darskus, R. 1977. Hydrolysis of chlorflurenol ME-methyl. Unpublished study performed by CELAMERCK. Gmbh & Co.
KG, Rhein, Germany, compiled and submitted by SRS International Corporation, Washington, DC, an agent for Nita Industries,
Inc. Study No. CFM-NITA-1611.
Doebbler, G.F. 1981. Soil adsorption/desorption of chlorflurenol ME-methyl ester. Unpublished study performed by Union
Carbide Corporation Environmental Services, Tarrytown, NY; sponsored by EM Industries, Inc., Elmsford, NY; and submitted
by Nita Industries, Inc., (location not reported). Study Number CFM-NITA-1631. UCCES Project No. 11507-86. EPA Case
Number 2095. Active Ingredient Number 98801.
Schluter, H. 1981. Leaching of 14C-chlorflurenol ME-methyl. Unpublished study performed by Celamerck GmbH & Co. KG,
Ingelheim/Rhein, Germany and submitted by Nita Industries, Inc., (location not reported). Study Number CFM-NITA-1631.
CM Document No. 109AA-922-003. EPA Case Number 2095. Active Ingredient Number 98801.
Sieper, H. 1969. Aerobic soil metabolism study. Unpublished study performed by E. MERCK AG, Darmstadt, Germany,
compiled and submitted by SRS International Corporation, Washington, DC, an agent for Nita Industries, Inc. Study No. CFM-
NITA-1621.
Ecological Effects MRID Studies Submitted to EPA
MRID 00082863
Frohberg, H., A. Metallinos, H. Pies, et al. 1975. Chronic Toxicity Test with IT 3456 in Beagle Dogs: Administration with the
Food over a Period of Two Years. (Translation; unpublished study received Apr 25, 1978 under 21137-EX-3; prepared by E.
Merck, West Germany, submitted by EM Laboratories, Inc., Elms- ford, NY.; CDL:097056-A)
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MRID 43355402 Wnorowski, G. 1994. Acute Oral Toxicity Limit Test: (Chlorflurenol ME Methyl): Lab Project Number: 3170. Unpublished
study prepared by Product Safety Labs. 16 p.
MRID 43595401 Estop, C. and R. Teske. 1969. Acute Oral Toxicity of Chlorflurenol ME Methyl Ester in Bobwhite Quail: Lab Project Number:
CFM-NITA-711A: S-404. Unpublished study prepared by Hill Top Research, Inc. 29 p.
MRID 43623601 Pedersen, C. and A. Solatycki. 1995. 8-Day Acute Dietary LC50 Study with Chlorflurenol ME Methyl in Bobwhite Quail: Lab
Project Number: 152-001-01. Unpublished study prepared by Bio-Life Associates, Inc. 48 p.
MRID 43623602 Pedersen, C. and A. Solatycki. 1995. 8-Day Acute Dietary LC50 Study with Chlorflurenol ME Methyl in Mallard Ducklings:
Lab Project Number: 152-002-02. Unpublished study prepared by Bio-Life Associates, Inc. 46 p.
MRID 45190901 Muller, W. 2000. Chlorflurenol ME-Methyl, Technical Oral (Gavage) Teratogenicity Study in the Rat: Lab Project Number:
926-460-028: 460-028. Unpublished study prepared by Hazleton Laboratories Deutschland GmbH. 222 p.
Open Literature and Government Reports
Beyer, W. N.; Connor, E; Gerould, S. 1994. Survey of soil ingestion by wildlife. Journal of Wildlife Management 58:375-382.
Fletcher, J.S., J.E. Nellesson and T. G. Pfleeger. 1994. Literature review and evaluation of the EPA food-chain (Kenaga) nomogram, an instrument for
estimating pesticide residues on plants. Environ. Tox. And Chem. 13(9): 1383-1391.
Hoerger, F. and E.E. Kenaga. 1972. Pesticide residues on plants: correlation of representative data as a basis for estimation of their magnitude in the
environment. IN: F. Coulston and F. Corte, eds., Environmental Quality and Safety: Chemistry, Toxicology and Technology. Vol 1. George Theime
Publishers, Stuttgart, Germany, pp. 9-28.
Kirkwood, RC. 1983. The relationship of metabolism studies to the modes of action of herbicides. Pestic. Sci. 14: 453-460.
Robinson, R. W., D. J. Cantliffe, and S. Shannon. 1971. Morphactin-induced parthenocarpy in the cucumber. Science 171: 1251-1252.
Snyder, J. C., C. Carter, and D. E. Knavel. 1983. Chlorflurenol ME interrupts ovule development of muskmelon. HortScience 18:345-347.
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T-REX. 2005. Terrestrial Residue Exposure Model (T-REX), Version 1.2.3. August 8, 2005. Environmental Fate and Effects Division, Office of
Pesticide Programs, U.S. Environmental Protection Agency, Washington, B.C.
U.S. EPA. 1993. U. S. Environmental Protection Agency. Wildlife Exposure Factors Handbook. Volume I of II. EPA/600/R-93/187a. Office of
Research and Development, Washington, B.C. 20460.
U.S. EPA. 2001. U.S. Environmental Protection Agency. Ecological Risk Assessor Orientation Package. U.S. Environmental Protection Agency,
Ecological Fate and Effects Division. Draft Version, August 2001.
U.S. EPA. 2004. U.S. Environmental Protection Agency. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs,
U.S. Environmental Protection Agency: Endangered and Threatened Species Effects Determinations. Office of Prevention, Pesticide, and Toxic
Substances. January 23.
Urban, D.J. and N.J. Cook. 1986. Hazard Evaluation Division Standard Evaluation Procedure Ecological Risk Assessment. EPA 540/9-85-001. U.S.
Environmental Protection Agency, Office of Pesticide Programs, Washington, DC.
Willis and McDowell. 1987. Pesticide persistence on foliage. Environ. Contam. Toxicol. 100:23-73.
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