Document ID: EPA-HQ-OPP-2005-0536-0005
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-12-20T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

     OFFICE OF	

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

 

Date: August 15, 2006

MEMORANDUM

SUBJECT:	  SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1 Fluroxypyr: Human
Health Risk Assessment for Proposed Uses on Dry Bulb 			  SEQ CHAPTER \h
\r 1 Onion, Including Garlic and Shallot. 

PC Code:   SEQ CHAPTER \h \r 1 128968 & 128959, Petition No: 3E6775 

DP Barcode: D314019. EPA Reg. No. 62719-285

		Regulatory Action: E Petition; IR4; Minor Use

		Risk Assessment Type: Single Chemical Aggregate

FROM:	Mary Clock-Rust, Biologist, RAB1

Donna S. Davis, Senior Chemist, RRB1

Kelly O’Rourke, Biologist, RAB3

		Amelia Acierto, Chemist, RAB3

		Health Effects Division (7509P)

THROUGH:	Steve Dapson, Senior Toxicologist

		Paula Deschamp, Chief

		Registration Action Branch 3

		Health Effects Division (7509P)

TO:		Barbara Madden

		Risk Integration, Minor Use, Emergency Response Branch

Registration Division (RD, 7505P)

  SEQ CHAPTER \h \r 1 The Health Effects Division (HED) of the Office of
Pesticide Programs (OPP) is charged with estimating the risk to human
health from exposure to pesticides.  The Registration Division (RD) of
OPP has requested that HED evaluate hazard and exposure data and conduct
dietary, occupational, and aggregate exposure assessments, to estimate
the risk to human health that will result from proposed use of
fluroxypyr on dry bulb onions (including garlic and shallots).  A
summary of the f  SEQ CHAPTER \h \r 1 indings and an assessment of human
risk resulting from the registered and proposed uses for fluroxypyr are
provided in this document.  The human health risk assessment was
prepared by Mary Clock-Rust and Donna Davis.  The toxicology assessment
was performed by Meta Bonner.  The residue chemistry reviews and dietary
exposure assessment were performed by Amelia Acierto, Donna Davis and
LaShonia Richardson.  The occupational/residential assessment was
performed by Kelly O’Rourke.  The drinking water exposure assessment
was performed by Ibrahim Abdel-Saheb of the Environmental Fate & Effects
Division (EFED).  

NOTE:  HED recently completed a Section 3 risk assessment for the use of
fluroxypyr   SEQ CHAPTER \h \r 1 in/on field corn, sweet corn, sorghum,
range and pasture grasses, and turf (8/28/2003; D284007). .  This
document contains only those aspects of the risk assessment that are
affected by the addition of the new uses of fluroxypyr on dry bulb
onions, shallots and garlic.  The following information from the last
risk assessment can be applied directly to this action (memo, 8/28/2003;
D284007):

Hazard Assessment and Dose-Response Assessment (Section 3.0; pp. 11-19) 

Residential Exposure and Risk Assessment (Section 4.4; pp. 27-32).

	

In this memo, dietary, occupational and aggregate risks were
re-evaluated based on the addition of aforementioned crops and use sites
to the fluroxypyr registration.

Table of Contents

  TOC \o "1-3" \h \z \u    HYPERLINK \l "_Toc143405357"  1.0	Executive
Summary	  PAGEREF _Toc143405357 \h  4  

  HYPERLINK \l "_Toc143405358"  2.0	Ingredient Profile	  PAGEREF
_Toc143405358 \h  8  

  HYPERLINK \l "_Toc143405359"  2.1	Summary of Registered/Proposed Uses	
 PAGEREF _Toc143405359 \h  8  

  HYPERLINK \l "_Toc143405360"  2.2	Structure and Nomenclature	  PAGEREF
_Toc143405360 \h  10  

  HYPERLINK \l "_Toc143405361"  2.3	Physical and Chemical Properties	 
PAGEREF _Toc143405361 \h  11  

  HYPERLINK \l "_Toc143405362"  3.0	Hazard Characterization/Assessment	 
PAGEREF _Toc143405362 \h  11  

  HYPERLINK \l "_Toc143405363"  3.2	FQPA Considerations	  PAGEREF
_Toc143405363 \h  12  

  HYPERLINK \l "_Toc143405364"  3.3	Dose-Response Assessment	  PAGEREF
_Toc143405364 \h  13  

  HYPERLINK \l "_Toc143405365"  3.6	Endocrine Disruption	  PAGEREF
_Toc143405365 \h  15  

  HYPERLINK \l "_Toc143405366"  4.0	Dietary Exposure/Risk
Characterization	  PAGEREF _Toc143405366 \h  15  

  HYPERLINK \l "_Toc143405367"  4.1	Pesticide Metabolites and Degradates
of Concern	  PAGEREF _Toc143405367 \h  15  

  HYPERLINK \l "_Toc143405368"  4.2	Drinking Water Residue Profile	 
PAGEREF _Toc143405368 \h  16  

  HYPERLINK \l "_Toc143405369"  4.3	Food Residue Profile	  PAGEREF
_Toc143405369 \h  17  

  HYPERLINK \l "_Toc143405370"  4.4	International Residue Limits	 
PAGEREF _Toc143405370 \h  18  

  HYPERLINK \l "_Toc143405371"  4.5	Dietary Exposure and Risk	  PAGEREF
_Toc143405371 \h  18  

  HYPERLINK \l "_Toc143405372"  4.5.1	Acute Dietary Exposure/Risk	 
PAGEREF _Toc143405372 \h  18  

  HYPERLINK \l "_Toc143405373"  4.5.2	Chronic Dietary Exposure/Risk	 
PAGEREF _Toc143405373 \h  18  

  HYPERLINK \l "_Toc143405374"  5.0	Residential (Non-Occupational)
Exposure/Risk Characterization	  PAGEREF _Toc143405374 \h  19  

  HYPERLINK \l "_Toc143405375"  5.1	Residential Handler Exposure	 
PAGEREF _Toc143405375 \h  20  

  HYPERLINK \l "_Toc143405376"  5.2	Residential Post-Application
Exposure	  PAGEREF _Toc143405376 \h  21  

  HYPERLINK \l "_Toc143405377"  6.0	Aggregate Risk Assessments and Risk
Characterization	  PAGEREF _Toc143405377 \h  22  

  HYPERLINK \l "_Toc143405378"  6.1	Acute Aggregate Risk	  PAGEREF
_Toc143405378 \h  22  

  HYPERLINK \l "_Toc143405379"  6.2	Short-Term and Intermediate Term
Aggregate Risk	  PAGEREF _Toc143405379 \h  22  

  HYPERLINK \l "_Toc143405380"  6.3	Long-Term/Chronic Aggregate Risk	 
PAGEREF _Toc143405380 \h  24  

  HYPERLINK \l "_Toc143405381"  7.0	Cumulative Risk
Characterization/Assessment	  PAGEREF _Toc143405381 \h  26  

  HYPERLINK \l "_Toc143405382"  8.0	Occupational Exposure/Risk Pathway	 
PAGEREF _Toc143405382 \h  26  

  HYPERLINK \l "_Toc143405383"  8.1	Short-/Intermediate-/Long-Term
Handler Risk	  PAGEREF _Toc143405383 \h  26  

  HYPERLINK \l "_Toc143405384"  8.2	Post-Application Risk	  PAGEREF
_Toc143405384 \h  28  

  HYPERLINK \l "_Toc143405385"  9.0	Data Needs and Label Requirements	 
PAGEREF _Toc143405385 \h  28  

  HYPERLINK \l "_Toc143405386"  9.1	Toxicology	  PAGEREF _Toc143405386
\h  28  

  HYPERLINK \l "_Toc143405387"  9.2	Residue Chemistry	  PAGEREF
_Toc143405387 \h  28  

  HYPERLINK \l "_Toc143405388"  9.3	Occupational/Residential Exposure	 
PAGEREF _Toc143405388 \h  28  

 1.0	Executive Summary  TC \l1 "1.0	Executive Summary 

  SEQ CHAPTER \h \r 1 

HED has conducted a human health risk assessment for fluroxypyr for the
purpose of making a tolerance/registration eligibility decision to
establish uses in or on dry bulb onion (including garlic and shallots)
as requested by the Interregional Research Project No. 4 (IR-4).

IR-4, on behalf of the Agricultural Experiment Stations of Colorado,
Idaho and Oregon, has proposed, in PP#3E6775, the establishment of a
permanent tolerance for residues of the herbicide, fluroxypyr
methylheptyl ester [((4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy)
acetic acid, 1-methylheptyl] and its metabolite fluroxypyr
[((4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy) acetic acid], free and
conjugated, all expressed as fluroxypyr, in or on dry bulb onion at 0.03
ppm, garlic at 0.03 ppm, and shallots at 0.03 ppm.

  SEQ CHAPTER \h \r 1 Fluroxypyr is a member of the pyridinoxy acid
class of herbicides.  Other chemicals in this class include triclopyr,
picloram, and clopyralid.  Fluroxypyr induces auxin-type responses in
susceptible annual and perennial broadleaf weeds.  

s that the end use product, Starane™  SEQ CHAPTER \h \r 1  is
formulated with the methylheptyl ester of fluroxypyr.  The pesticide
active ingredient is the acid form of fluorxypyr; therefore, throughout
the document, the terms active ingredient (ai) and acid equivalent (ae)
may be used interchangeably.  

Background

In June 1998, HED completed a human health risk assessment for uses of
fluroxypyr in/on barley, oats, wheat, milk, and livestock commodities. 
Permanent tolerances have been established under 40 CFR §180.535 for
the combined residues of fluroxypyr 1-MHE and fluroxypyr acid for these
uses.  In addition, Section 18 risk assessments were completed for use
on corn in June 1998, grass pastures and rangeland in May 2001, and
grain sorghum in August 2002.  The most recent Section 3 HED human
health risk assessment was performed in 2003 in conjunction with a
petition for the use of fluroxypyr in/on   SEQ CHAPTER \h \r 1 in/on
field corn, sweet corn, sorghum, range and pasture grasses, and turf
(8/28/2003; D284007).  

There are currently no Codex, Canadian, or Mexican maximum residue
limits (MRLs) for fluroxypyr or its metabolites in/on dry bulb onions;
therefore this action does not raise international harmonization issues.

Proposed Uses

The end-use product for this action is Starane™ EC herbicide, an
emulsifiable concentrate formulation of 26.2% fluroxypyr 1-MHE.  The
active ingredient is the acid form of fluroxypyr.  Starane™ contains
1.5 lb ai/gal.  The proposed use is as two foliar broad cast
applications to dry bulb onions including garlic and shallots.  The
first application is to be applied when the dry bulb onion is at 3 – 5
true leaves at a rate of 0.125 lbs ai/A.  The second application is at a
minimum retreatment interval of 19 days and a minimum PHI of 42 days at
a rate of 0.25 lbs ai/A.  The seasonal maximum stated application rate
is 0.375 lbs ai/A.

Hazard Assessment

There are no changes to the hazard assessment from the previous Section
3 risk document (Memo, M. Bonner, D284007, 8/28/2003).  The hazard
profile for fluroxypyr is summarized below.  

Fluroxypyr has low acute toxicity by the oral and dermal routes and
moderate acute toxicity by the inhalation route.  It is not irritating
to the skin, nor is it a dermal sensitizer, however, it is a mild eye
irritant.  Subchronic and chronic studies in rats, mice, and dogs
indicate that fluroxypyr administration results in kidney toxicity.  In
the rat, the 90-day feeding study resulted in significant nephrotoxicity
and death at the high dose; the chronic study in rats showed chronic
progressive glomerulonephropathy; the multi-generation reproductive
study also showed kidney effects with increased kidney weight and
associated microscopic findings.  In the dog, at 28-days, kidney
toxicity was noted; early signs of acute tubular nephrosis were seen in
both sexes of dogs.  In the mouse, increased kidney lesions were
observed in the chronic study.  Developmental studies and the
reproductive study in rats indicated maternal toxicity as increased
kidney weight, decreased body-weight gain and food consumption.  In
developmental studies with both rats and rabbits, deaths at high doses
were observed.  The HED Hazard Identification Assessment Review
Committee (HIARC) concluded that there was no evidence
(quantitative/qualitative) of increased susceptibility following in
utero exposure to fluroxypyr in rats and rabbits, or following pre
and/or postnatal exposure in rats. A review of acceptable
carcinogenicity and mutagenicity studies provide no indication that
fluroxypyr is carcinogenic or mutagenic.

Based on EPA Proposed Guidelines for Carcinogen Risk Assessment (April
10, 1996), Fluroxypyr was classified as a "not likely" human carcinogen.
 

Dose Response Assessment and Food Quality Protection Act (FQPA) Decision

On April 10, 2003 the HIARC evaluated the toxicology endpoint selection
and potential for increased susceptibility of infants and children from
exposure to fluroxypyr with regard to the acute and chronic Reference
Doses (RfDs) and for use as appropriate in occupational/residential
exposure/ risk assessments.  At the April, 2003 meeting, the special
FQPA SF was reduced to 1x based on toxicological considerations by the
HIARC, the low degree of concern and lack of residual uncertainties for
pre- and post-natal toxicity, and the completeness of the residue
chemistry and environmental fate databases (evaluated by the risk
assessment team).



Table 1.  Summary of Toxicological Doses used in the Current Risk
Assessment

Exposure Scenario	Dose	LOC

Acute dietary (all populations)	An endpoint attributable to a single
exposure was not identified; risk assessment is not required

Chronic dietary	Oral NOAEL=100 mg/kg/day	chronic RfD and cPAD=1
mg/kg/day

Short- and intermediate-term incidental oral	Oral NOAEL=100 mg/kg/day
LOC=100

dermal (all intervals)	Quantification not required since 21 day dermal
NOAEL=1000 mg/kg/day

Short-, intermediate- and long-term inhalation	Oral NOAEL=100 mg/kg/day
LOC for MOEs < 100 (occupational)

Cancer (oral, dermal, inhalation)	Not likely to be carcinogen; cancer
risk assessments are not required

Dietary Exposure Estimates (Food Only) 

An endpoint attributable to a single exposure was not identified;
therefore, an acute dietary risk assessment was not performed.

An unrefined, Tier 1 chronic dietary-exposure assessment was conducted
for all supported fluroxypyr food uses.  In this assessment, it was
assumed that all of the crops included in the analysis were treated
(i.e., 100% crop treated) with fluroxypyr.  These assumptions result in
highly conservative estimates of dietary exposure and risk.  In
calculating dietary risk estimates, HED has compared the chronic
population-adjusted dose (cPAD) to the estimated dietary exposure from
the DEEM-FCID™ model.  Typically, HED has concerns regarding dietary
risk when the exposure estimates exceed 100% of the cPAD.  Even with the
conservative assumptions noted above, risk estimates associated with
dietary exposure to fluroxypyr are significantly below HED’s level of
concern.  The existing and proposed uses (food only) result in an
exposure to the U.S populations which is <1% of the cPAD.  The most
highly exposured subpopulation is children 1-2 years of age with an
exposure (food only) equivalent to 1.4% of the cPAD.  

A cancer risk assessment was not conducted since fluroxypyr has been
classified as “not likely” to be carcinogenic.

Drinking Water Exposure Estimates

Drinking water estimated environmental concentrations (EECs) of
fluroxypyr are based on application to rangeland and pastureland
grasses, the exposure scenario which EFED has determined to be the
scenario which will lead to the highest environmental concentrations. 
There are no monitoring data for fluroxypyr in surface or groundwater. 
The surface water EEC for use in the chronic dietary (food and
water)risk assessment was derived using the Tier II PRZM/EXAMS model
with the Index Reservoir and Percent Crop Area Adjustment.  The model
predicts a surface water annual mean value of 3.3 ppb.  The ground water
EEC was developed using the Tier I  Screening Concentration in Ground
Water (SCI-GROW) model.  This model predicts a chronic groundwater value
of 0.04 ppb.  For the chronic dietary exposure and risk assessment (food
and water), HED has used the higher value, the surface water EEC of  3.3
ppb. 

Residential Exposure Estimates

There are no additional residential exposures expected from the proposed
registration of fluroxypyr on onion.  Fluroxypyr is registered for use
on residential turfgrass and recreational sites such as golf courses,
parks, and sports fields.  An assessment of the residential risks was
performed as part of the last risk assessment.  Residential risk
estimates (from inhalation and incidental oral exposure) were used in
this risk assessment in calculating short-term aggregate risk. 
Short-term inhalation exposure is possible for residential handlers and
toddlers may experience short-/ intermediate-term exposure to fluroxypyr
via incidental non-dietary ingestion (i.e., hand-to-mouth,
object-to-mouth (turfgrass), and soil ingestion) during post-application
activities on treated turf.   All calculated residential MOEs are
greater than the target of 100, and therefore, not of concern to HED.

Aggregate Exposure Scenarios and Risk Conclusions					

For the proposed uses, human health aggregate risk assessments have been
conducted for the chronic aggregate exposure (food + drinking water)
scenario, as well as the short-/intermediate-term aggregate exposure
scenario.  A cancer aggregate risk assessment was not performed because
fluroxypyr is classified as a “not likely” human carcinogen.  

The existing and proposed uses result in long-term aggregate dietary
exposure to the U.S population which is <1% of the cPAD.  Drinking water
was included in the dietary assessment.  Dietary risk results are the
same for individuals exposed to fluroxypyr in food alone or food plus
drinking water.  The most highly exposed subpopulation is children 1-2
years of age with an aggregate exposure (food and water) equivalent to
1.4% of the cPAD.  

All potential exposure pathways were assessed in the aggregate risk
assessment.  None of the aggregate exposure and risk estimates exceed
HED's level of concern.

Occupational Exposure Estimates

There is a potential for occupational exposure to fluroxypyr during
mixing, loading, application, and post-application activities.  The
occupational risk assessment was based on inhalation exposure only.  

entry interval (REI) is required for chemicals classified under Toxicity
Category III or IV.  The current Starane™ label has a 12-hour REI,
which complies with the WPS.  

Recommendations for Tolerances

Provided the registrant provides a label consistent with the
Administrative volume submitted in support of the requested new use on
bulb onions (including garlic and shallot), and further, provided the
residue chemistry deficiencies described in Section 8.1 are addressed as
a condition of the registration, there are no human health risk
assessment issues which would preclude the registration and
establishment of permanent tolerance for residues of the herbicide
fluroxypyr methylheptyl ester
[((4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy) acetic acid,
1-methylheptyl] and its metabolite fluroxypyr
[((4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy) acetic acid], free and
conjugated, all expressed as fluroxypyr, in or on the following
commodities:

	Onion, bulb………………….0.03 ppm

	Garlic, bulb………………….0.03 ppm

	Shallot, bulb…………………0.03 ppm

2.0	Ingredient Profile  TC \l1 "2.0	Ingredient Profile 

2.1	Summary of Registered/Proposed Uses

The end-use product for this action is Starane™ EC herbicide, an
emulsifiable concentrate formulation of 26.2% fluroxypyr 1-MHE.  The
active ingredient is the acid form of fluroxypyr.  Starane™ contains
1.5 lb ai/gal.  The proposed use is as two foliar broad cast
applications to dry bulb onions including garlic and shallots.  The
first application is to be applied when the dry bulb onion is at 3 – 5
true leaves at a rate of 0.125 lbs ai/A.  The second application is at a
minimum retreatment interval of 19 days and a minimum PHI of 42 days at
a rate of 0.25 lbs ai/A.  The seasonal maximum stated application rate
is 0.375 lbs ai/A.  The use directions submitted as part of the
administrative volume are adequately supported by the submitted dry bulb
onion field trial data.  HED notes that the residue data submitted in
support of this action were developed using the Vista formulation.  HED
has confirmed with IR-4 (email from L. Richardson to D. Davis dated
7/21/2006) that the Vista formulation are the Starane™ formulation are
of sufficiently similar composition such that residue data generated
with Vista are likely to yield substantially similar residue profiles as
data generated with the Starane™ formulation. 

HED has not received a proposed label for the use of Starane™ in/on
dry bulb onions (including garlic and shallots).  Prior to registration
of Starane™ for use on dry bulb onions the petitioner should provide a
label for Agency review which specifies the application rates, timing,
PHI and seasonal maximum rate consistent with the proposed use pattern
described in the administrative volume submitted to support this action.
 

b onion residue data submitted with this petition.  However, prior to
registration of Starane™ for use on dry bulb onion (including garlic
and shallot), the petitioner should submit a copy of the proposed label
for review which are consistent with the proposed use pattern in the
administrative volume that accompanied this petition.  

  TC \l2 "2.1	Summary of Registered/Proposed Uses 

Table 2.1.	Summary of Directions for Use of Fluroxypyr

Applic. Timing, Type, and Equip.	Formulation

[EPA Reg. No.]	Applic. Rate

(lb ai/A)	Max. No. Applic. per Season	Max. Seasonal Applic. Rate (lb
ai/A)	PHI (days)	Use Directions and Limitations

Onion

Make one foliar, broadcast application when dry bulb onions are 3-5 true
leaves.

Make second, foliar, broadcast, application 21 +/-2 days after first
application, at 45 +/-3 days before harvest.	Starane™

62719-286	0.125-0.25	2	0.375 	45 (+/-3)	Max total spray per acre 10-40
gallons.

2.2	Structure and Nomenclature  TC \l2 "2.2	Structure and Nomenclature 

Table 2.2.	Fluroxypyr Nomenclature

Chemical Structure	

Empirical Formula	  SEQ CHAPTER \h \r 1 C15H21Cl2FN2O3	

Common name	  SEQ CHAPTER \h \r 1 Fluroxypyr 1-methylheptyl ester

Company experimental name	XRM-5316

IUPAC name	((4-amino-3.5-dichloro-6-fluoro-2-pyridinyl)oxy)acetic acid,
1-methylheptyl ester

CAS name

	CAS Registry Number	  SEQ CHAPTER \h \r 1 81406-37-3

End-use product/EP	StaraneTM and VistaTM

Chemical Class	pyridinoxy acid class of herbicides

Known Impurities of Concern	None

The molecular structure of fluroxypyr’s acid metabolite is shown
below.

2.3	Physical and Chemical Properties  TC \l2 "2.3	Physical and Chemical
Properties 

C

pH	  SEQ CHAPTER \h \r 1 6.81 in a solution containing 90.1 mg/L

Density	  SEQ CHAPTER \h \r 1 1.30 g/mL at 21C

Water solubility (20°C)	  SEQ CHAPTER \h \r 1 90.1 mg/L in purified
water

Solvent solubility (temperature not specified)	  SEQ CHAPTER \h \r 1 294
g/L in pH 5 buffer

136 g/L in pH 7 buffer

57.2 g/L in pH 9 buffer

6.23 g/100 mL in n-heptane

>200 g/100 mL in xylene

377 g/100 mL in methanol

22.0 g/100 mL in n-octanol

>300 g/100 mL in acetone

Vapor pressure (25°C)	  SEQ CHAPTER \h \r 1 2.0 x 10-5 kPa at 25C

1.0 x 10-5 kPa at 20C

Dissociation constant, pKa

	Octanol/water partition coefficient, logPOW (25°C)	  SEQ CHAPTER \h \r
1 log10 Kow = 5.04 at pH 7

3.0	Hazard Characterization/Assessment

  TC \l1 "3.0	Hazard Characterization/Assessment 

The Hazard database is complete for the purposes of this assessment on
dry bulb onions.  No new information has been submitted or reviewed
since the last hazard assessment document (Fluroxypyr - Second Report of
the Hazard Identification Assessment Review Committee. June 26, 2003.
TXR NO. 0051987); therefore, a summary of the hazard assessment has been
 provided below.  For details, please refer to the HIARC report Memo, M.
Bonner, 06/26/2003; TXR NO. 0051987).

3.1	Toxicological Effects  TC \l3 "3.1.2	Toxicological Effects 

  SEQ CHAPTER \h \r 1 

Fluroxypyr has low acute toxicity by the oral and dermal routes and
moderate acute toxicity by the inhalation route.  The MHE form of
fluroxypyr is less toxic for the acute oral route (toxicity category IV)
and the acid form is more toxic by the acute inhalation route (toxicity
category II).  It is not irritating to the skin, nor is it a dermal
sensitizer, however, it is a mild eye irritant.  The acute toxicity of
fluroxypyr technical is summarized in the table in the appendix. 

  SEQ CHAPTER \h \r 1 Subchronic and chronic studies indicate that
fluroxypyr administration results in kidney toxicity.  In the rat, the
90-day feeding study resulted in significant nephrotoxicity and death at
the high dose, the chronic study in rats showed chronic progressive
glomerulonephropathy in both sexes, and the multi-generation
reproductive study also showed kidney effects.  At 28-days, kidney
toxicity was also noted in dogs; seen as early signs of acute tubular
nephrosis were seen in both sexes of dogs.  Increased kidney lesions
were observed in the chronic mouse study.  However, no treatment related
toxicity was seen in studies with the subchronic treated mice or chronic
treated dogs.  At high dosing, treatment related deaths were noted for
rats (starting at 500 mg/kg/day) and for rabbits (starting at 400
mg/kg/day).

  SEQ CHAPTER \h \r 1 Developmental studies and the reproductive study
in rats indicated maternal toxicity as increased kidney weights,
decreased body-weight gains and food consumption, and in developmental
studies with both rats and rabbits, deaths at high doses were observed
(600 mg/kg/day for the former and 500 mg/kg/day for the latter).  There
was no evidence (quantitative/qualitative) of increased susceptibility
following in utero exposure to the acid and the ester in rats and
rabbits, or following pre and/or postnatal exposure to the acid form in
rats.  There are no neurotoxicity concerns from the acute and subchronic
neurotoxicity studies.    SEQ CHAPTER \h \r 1 Fluroxypyr is classified
as “not likely” a human carcinogen and there was no concern for its
mutagenicity potential.  Fluroxypyr  SEQ CHAPTER \h \r 1  is negative
for mutagenic/genotoxic potential in a battery of mutagenicity studies. 
For more details on the hazard profile for fluroxypyr, please see the
HIARC report.

3.2	FQPA Considerations  TC \l2 "3.3	FQPA Considerations 

  SEQ CHAPTER \h \r 1 

On April 10, 2003, the HED HIARC evaluated the potential for increased
susceptibility of infants and children from exposure to fluroxypyr
according to the February 2002 OPP 10X guidance document.  The HIARC
concluded that the toxicology database for fluroxypyr is adequate to
assess FQPA requirements and recommended that the special FQPA Safety
Factor be removed (i.e., reduced to 1X) due to the lack of concern or
residual uncertainties for pre-and/or post natal toxicity.  Likewise,
the fluroxypyr risk assessment team evaluated the quality of the
exposure data; and, based these data, agreed that the special FQPA SF
could be reduced to 1X.  The recommendation is based on the following:  
 SEQ CHAPTER \h \r 1 

There are no concerns or residual uncertainties for pre- and/or
post-natal toxicity.

There was no evidence of neurotoxicity or neuropathology in the
available studies.

The toxicological database is complete for FQPA assessment.

The chronic dietary food exposure assessment utilizes tolerance level
residue estimates and assumes 100 % CT for all commodities.  This
assessment is not likely to underestimate exposure/risk.

The dietary drinking water assessment utilizes water concentration
values generated by model and associated modeling parameters which are
designed to provide conservative, health protective, high-end estimates
of water concentrations which will not likely be exceeded.

The previous residential exposure assessment was conducted using
standard assumptions which are based on carefully reviewed data.

3.3	Dose-Response Assessment  TC \l2 "3.5	Hazard Identification and
Toxicity Endpoint Selection 

  SEQ CHAPTER \h \r 1 

On April 10, 2003 the HIARC reevaluated the toxicology endpoint
selection for potential for increased susceptibility of infants and
children from exposure to fluroxypyr with regard to the acute and
chronic Reference Doses (RfDs) and for use as appropriate in
occupational/residential exposure/ risk assessments.  The toxicology
database had previously been evaluated by the HIARC in January 1998. 
The potential for increased susceptibility of infants and children from
exposure to fluroxypyr was also evaluated as required by the Food
Quality Protection Act (FQPA) of 1996 according to the 2002 OPP 10X
Guidance Document.  The doses and toxicological endpoints selected for
various exposure scenarios are discussed below and summarized in Table
3.3 below.  For details about the hazard profile for fluroxypyr, please
see the HIARC report.



Table 3.3.  Summary of Toxicological Doses and Endpoints for Fluroxypyr
for Use in Human Risk Assessments

Exposure

Scenario	Dose Used in Risk Assessment, UF 	FQPA SF* and Level of Concern
for Risk Assessment	Study and Toxicological Effects

Acute Dietary

(All populations)	NOAEL = NA 

UF = NA

Acute RfD = NA 	FQPA SF = NA

aPAD = acute RfD

              FQPA SF

= NA	No adverse effects were identified following a single oral dose.

Chronic Dietary

(All populations)	NOAEL= 100 mg/kg/day

UF = 100

Chronic RfD = 

1 mg/kg/day	FQPA SF = 1x

cPAD = 

chronic RfD

 FQPA SF

= 1 mg/kg/day	Chronic/Onco-Rat

LOAEL = 100 mg/kg/day based on kidney effects.

Short-Term 

Incidental Oral 

(1-30 days)

	NOAEL= 100 mg/kg/day	Residential LOC for MOE = 100 

Occupational = NA	Chronic/Onco-Rat

LOAEL = 100 mg/kg/day based on kidney effects.

Intermediate-Term 

Incidental Oral 

(1- 6 months)	NOAEL= 100 mg/kg/day	Residential LOC for MOE = 100 

Occupational = NA	Chronic/Onco-Rat

LOAEL = 100 mg/kg/day based on kidney effects.

Dermal 

(All durations)	Dermal (or oral) study NOAEL= 

NA

	Residential LOC for MOE = NA 

Occupational LOC for MOE = NA	Quantification not required since 21-Day
dermal rabbit NOAEL = 1000 mg/kg/day and there is no developmental or
neurological toxicity concern.

 Inhalation 

(All durations)

	Inhalation (or oral) study NOAEL= 100 mg/kg/day

(inhalation absorption rate = 100%)	Residential LOC for MOE = 100 

Occupational LOC for MOE = 100 	Chronic/Onco-Rat

LOAEL = 100 mg/kg/day based on kidney effects.

Cancer (oral, dermal, inhalation)			Classification: “not likely”
human carcinogen

UF = uncertainty factor, FQPA SF = FQPA safety factor, 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

  SEQ CHAPTER \h \r 1 Recommendation for Aggregate Exposure Risk
Assessments: As per FQPA, 1996, when there are potential residential
exposures to the pesticide, aggregate risk assessment must consider
exposures from three major sources: oral, dermal and inhalation
exposures.  The toxicity endpoints selected for these routes of exposure
may be aggregated as follows: For Short- Intermediate- and Long-Term
aggregate exposure risk assessments, the oral and inhalation routes can
be combined since, oral equivalent doses were used for inhalation
exposure risks.  Quantification of dermal risk is not required for any
time period.

3.6	Endocrine Disruption  TC \l2 "3.6	Endocrine disruption 	

EPA is required under the FFDCA, as amended by FQPA, to develop a
screening program to determine whether certain substances (including all
pesticide active and other ingredients) "may have an effect in humans
that is similar to an effect produced by a naturally occurring estrogen,
or other such endocrine effects as the Administrator may designate." 
Following the recommendations of its Endocrine Disruptor Screening and
Testing Advisory Committee (EDSTAC), EPA determined that there were
scientific bases 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 and, to the extent that effects in wildlife may help
determine whether a substance may have an effect in humans, FFDCA
authority to require the wildlife evaluations.  As the science develops
and resources allow, screening of additional hormone systems may be
added to the Endocrine Disruptor Screening Program (EDSP).

				

When the appropriate screening and/or testing protocols being considered
under the Agency’s EDSP have been developed, fluroxypyr may be
subjected to additional screening and/or testing to better characterize
effects related to endocrine disruption.

4.0	Dietary Exposure/Risk Characterization

4.1	Pesticide Metabolites and Degradates of Concern TC \l3 "5.1.8
Pesticide Metabolites and Degradates of Concern 

Table 4.1  Summary of Metabolites and Degradates to be included in the
Risk Assessment and Tolerance Expression for Fluoroxypyr

Matrix	Residues included in Risk Assessment	Residues included in
Tolerance Expression

Plants

	Primary Crop	Fluroxypyr 1-MHE and Fluroxypyr	Fluroxypyr 1-MHE and
Fluroxypyr

	Rotational Crop	Fluroxypyr 1-MHE and Fluroxypyr	Fluroxypyr 1-MHE and
Fluroxypyr

Livestock

	Ruminant	Fluroxypyr 1-MHE and Fluroxypyr	Fluroxypyr 1-MHE and
Fluroxypyr

	Poultry	Fluroxypyr 1-MHE and Fluroxypyr	Fluroxypyr 1-MHE and Fluroxypyr

Drinking Water

	Fluroxypyr 1-MHE and Fluroxypyr	Not Applicable

4.2	Drinking Water Residue Profile

EFED previously conducted an analysis to determine drinking water
estimated environmental concentrations (EECs) of fluroxypyr  based on
application to rangeland and pastureland grasses (D292471, Ibrahim
Abdel-Saheb, 8/13/03).  EFED has determined that the new proposed use on
onion, will not likely result in environmental concentrations above that
predicted from the grasses use (D314020, Ibrahim Abdel-Saheb, 2/15/06);
therefore the EECs determined previously will be used for this risk
assessment.    SEQ CHAPTER \h \r 1 EFED currently has no monitoring data
for fluroxypyr in surface or groundwater.  The Tier II screening models
PRZM and EXAMS with the Index Reservoir and Percent Crop Area adjustment
(IR-PCA PRZM/EXAMS) were used to determine estimated surface water
concentrations of fluroxypyr from its use on alfalfa in Texas. The
Screening Concentration in Groundwater (SCI-GROW) model was used to
estimate groundwater concentrations for fluroxypyr. Modeling results are
shown in Table 4.2.

Table 4.2. EWDCs for Fluroxypyr

Crop:  Alfalfa

	Model EECs (ppb)

Surface water/ peak (90th percentile annual daily max.)	32.9

Surface water/ 90th percentile  (annual mean)	3.28

Surface water (36-year overall mean )	1.76

Groundwater 	0.04

use(s) modeled	1 application @ 0.5 lb ai/acre, aerial application

PCA	0.87

The IR-PCA PRZM/EXAMS modeling results indicate that fluroxypyr has the
potential to contaminate surface waters by spray drift, and runoff in
areas with large amounts of annual rainfall. 

 TC \l3 "5.1.9	Drinking Water Residue Profile 

4.3	Food Residue Profile

  TC \l3 "5.1.10	Food Residue Profile 

Detailed residue chemistry considerations are contained in the
memorandum entitled Fluroxypyr:  Petition for Tolerance to Support Use
on Dry Bulb Onions, Including Garlic and Shallots.  Summary of
Analytical Chemistry and Residue Data.  PP# 3E6775 (D. Davis, D331225,
8/2/06).

The nature of the residue in dry bulb onions has not been adequately
delineated.  Given that this is a minor crop use; residues are expected
to be very low; there is low likelihood of a metabolite more toxic than
the parent based both on structure activity considerations and
information gleaned from the available metabolism data; and the dietary
risk assessment yields a very low level of risk, HED recommends
development of metabolism data to elucidate the nature of the residue in
bulb onions be a condition of the registration.

There are no animal feed items associated with this use on dry bulb
onions (including garlic and shallot); therefore, consideration of the
nature and/or magnitude of residues in animal commodities is not
pertinent to this action.

  SEQ CHAPTER \h \r 1 The GC/MSD analytical method used to determine
residues of fluroxypyr in both the acid and methylheptyl ester forms is
adequate to recover residues of fluroxypyr and fluroxypyr 1-MHE in dry
bulb onions.  The method converts the methylheptyl ester form of
fluroxypyr to the acid and results are reported as the acid equivalent. 
The lower limit of method validation (LLMV) for bulb onions was 0.01
ppm.  Further, the method is an adaptation of a Dow AgroSciences method
GRM 96.02, which has been adequately validated as an enforcement method;
therefore HED considers the modified method to be adequate to enforce
the requested tolerance, provided the registrant develops a confirmatory
method and submits a revised copy of the method specific to onions to
FDA for inclusion in PAM II.

  SEQ CHAPTER \h \r 1 Fluroxypyr has been tested through the FDAs
Multi-residue Methodology, Protocols C, D, and E.  The results have been
published in the FDA Pesticide Analytical Manual, Volume I.

Adequate storage stability data have been submitted which indicate that
residues of fluroxypyr and fluroxypyr 1-MHE (expressed as fluroxypyr
equivalents) stored at temperatures ranging from –27 °C to –13 °C 
are stable for a period of at least 279 days (fluroxypyr) or 284 days
(fluroxypyr 1-MHE).

The residue data submitted are of adequate geographic representation and
number to support the requested use.    SEQ CHAPTER \h \r 1 Residues of
fluroxypyr ranged from <0.01 ppm (the method LLMV) to 0.02 ppm in dry
bulb onions treated at a seasonal rate of up to 0.375 lbs ai/A with PHIs
ranging from 42 to 49 days.  These data support the requested tolerance
of 0.03 ppm for residues of fluroxypyr in/on dry bulb onions.

There are no processed commodities derived from dry bulb onions;
therefore, a discussion of processed commodities is not relevant to this
action.

Rotational crop issues have been address in conjunction with prior uses
on cereal grains.  No new rotational crop data are required to support
this action.

4.4	International Residue Limits

There are no Codex, Canadian or Mexican MRLs for fluroxypyr for dry bulb
onions; therefore, there are no issues of international harmonization
raised by this action.

4.5	Dietary Exposure and Risk TC \l2 "5.2  Dietary Exposure and Risk 

A chronic dietary exposure analysis was performed for the purposes of
this human health risk assessment (Memo, A. Acierto, D328732,
08/01/2006).  

4.5.1	Acute Dietary Exposure/Risk

An endpoint attributable to a single exposure was not identified;
therefore, an acute dietary risk assessment was not performed.

4.5.2	Chronic Dietary Exposure/Risk

The fluroxypyr chronic dietary exposure assessment was conducted using
DEEM-FCID( (Version 2.0), which incorporates consumption data from
USDA’s Continuing Surveys of Food Intakes by Individuals (CSFII),
1994-1996 and 1998.  The 1994-96, 98 data are based on the reported
consumption of more than 20,000 individuals over two non-consecutive
survey days.  Foods “as consumed” (e.g., apple pie) are linked to
EPA-defined food commodities (e.g. apples, peeled fruit - cooked; fresh
or N/S; baked; or wheat flour - cooked; fresh or N/S, baked) using
publicly available recipe translation files developed jointly by
USDA/ARS and EPA.  Consumption data are averaged for the entire U.S.
population and within population subgroups for chronic exposure
assessment, but are retained as individual consumption events for acute
exposure assessment.

For chronic exposure and risk assessment, an estimate of the residue
level in each food or food-form (e.g., orange or orange juice) on the
food commodity residue list is multiplied by the average daily
consumption estimate for that food/food form.  The resulting residue
consumption estimate for each food/food form is summed with the residue
consumption estimates for all other food/food forms on the commodity
residue list to arrive at the total average estimated exposure. 
Exposure is expressed in mg/kg body weight/day and as a percent of the
cPAD.  This procedure is performed for each population subgroup.

An unrefined, Tier 1 chronic dietary-exposure assessment was conducted
for all supported fluroxypyr food uses.  In this assessment, it was
assumed that all of the crops included in the analysis were treated
(i.e., 100% crop treated) with fluroxypyr.  These assumptions result in
highly conservative estimates of dietary exposure and risk.  Drinking
water residues were not included in this dietary assessment (for dietary
exposure including drinking water, see Section 6.0).  In calculating
dietary risk estimates, HED has compared the chronic population-adjusted
dose (cPAD) to the estimated dietary exposure from the DEEM-FCID™
model.  

Typically, HED has concerns regarding dietary risk when the exposure
estimates exceed 100% of the cPAD.  Even with the conservative
assumptions noted above, risk estimates associated with dietary exposure
to fluroxypyr are significantly below HED’s level of concern.  The
existing and proposed uses (food only) result in an exposure to the U.S
populations which is <1% of the cPAD.  The most highly exposured
subpopulation is children 1-2 years of age with an exposure (food only)
equivalent to 1.4% of the cPAD.  Results of the analysis are summarized
below.

Table 4.5.2   Summary of Dietary Exposure and Risk for Fluroxypyr

(Food Only)

Population Subgroup	Chronic Dietary

	

Exposure (mg/kg/day)	

% cPAD

U.S. Population (total)	

0.003183	

<1

All Infants (< 1 year old)	

0.004606	

<1

Children 1-2 years old	

0.013762	

1.4

Children 3-5 years old	

0.009731	

1.0

Children 6-12 years old	

0.005978	

<1

Youth 13-19 years old	

0.002851	

<1

Adults 20-49 years old	

0.001962	

<1

Females 13-49 years old	

0.001737	

<1

Adults 50+ years old	

0.001805	

<1

A cancer risk assessment was not conducted since fluroxypyr has been
classified as “not likely” to be carcinogenic.

5.0	Residential (Non-Occupational) Exposure/Risk Characterization  TC
\l1 "6.0	Residential (Non-Occupational) Exposure/Risk Characterization 

A residential exposure assessment for fluroxypyr was prepared in the HED
memorandum dated 8/28/03 (Memo, K. O’Rourke; D285872).   For details
on the residential exposure assessment, see pages 27-32 of the last HED
risk assessment for fluroxypyr (memo, M. Bonner, et al., 8/28/2003;
D284007).  

A product containing fluroxypyr (i.e., VistaTM) is registered for
application to residential turfgrass and recreational sites such as golf
courses, parks, and sports fields.  It may be applied to turf at rates
ranging from 0.125 to 0.47 lbs ai/A, but may not exceed 0.47 lbs
ai/A/yr.  The proposed label does not prohibit homeowners from
mixing/loading/applying VistaTM.  

Residential handlers may receive short-term dermal and inhalation
exposure to fluroxypyr when mixing, loading and applying the
formulations.  Adults and children may be exposed to fluroxypyr residues
from dermal contact with turf during post-application activities. 
Toddlers may receive short- and intermediate-term oral exposure from
incidental ingestion during post-application activities.  

In the last residential assessment, residential handler and
post-application risks were assessed.  For handlers, the lowest
inhalation MOE was 19,000,000 for mix/load and broadcast application of
liquid formulation (garden hose-end sprayer).

No chemical-specific exposure data for handler activities were submitted
to HED in support of the registered lawn uses.  A turf transferrable
residue (TTR) study was submitted by the registrant (MRID#45361602) that
was used in assessing post-application activities.  HED’s Draft
Standard Operating Procedures (SOPs) for Residential Exposure
Assessments, and Recommended Revisions (HED Policy Number 11, revised 22
Feb 2001), were used as the basis for all residential handler exposure
calculations.  Some of the handler exposure data used in this assessment
is from the Outdoor Residential Exposure Task Force (ORETF).   The ORETF
data were used in this assessment in place of PHED data for the garden
hose-end sprayer scenario.

5.1	Residential Handler Exposure TC \l2 "6.1	Residential Handler
Exposure 

Inhalation daily doses for residential handlers were calculated for the
emulsifiable concentrate formulation using data for
mixing/loading/applying a liquid.  As shown below, the inhalation MOEs
for residential handlers are well above the LOC of 100, and are not of
concern.  

				

Table 5.1.  Handler Exposure and Risk Estimates for Residential Lawn
Applicators

Handler

Scenario

	 Rate

(lb ae/

acre) 	Acres Treated

(acres/

day)	PHED 

Unit Exposure1

(mg/lb ai) 	Short-term Daily

Inh. Dose 2

(mg/kg/day)	Short-term

Inhalation MOE  3

1.  mix/load and spot application of liquid formulation (low-pressure
hand sprayer)	

0.47	

0.023	

0.030	

4.6E-06	

2.2E+07

2.  mix/load and broadcast application of liquid formulation (garden
hose-end sprayer)	

0.47	

0.5	

0.016	

5.4E-05	

1.9E+06

1 Data Confidence for inhalation unit exposures: 

		low-pressure hand sprayer:  80 replicates, ABC grade, medium
confidence (from PHED)

		garden hose-end sprayer: 30 replicates, A grade, high confidence (from
ORETF)

2 Daily Dose  =	[Rate (lb ae/A) x Acres Treated (A/day) x Unit
Exposure(mg/lb ai handled)] / Body Weight

3 MOE	  = 	NOAEL (100/kg/day) / Daily Inhalation Dose (mg/kg/day)

5.2	Residential Post-Application Exposure TC \l2 "6.2.	Residential 
Postapplication Exposure 

As noted previously, a dermal risk assessment for post-application
exposure was not conducted because a dermal endpoint was not selected by
the HIARC.  Therefore, only the following post-application exposure
scenarios resulting from lawn treatment were assessed: (1) toddlers’
incidental ingestion of pesticide residues on lawns from hand-to-mouth
transfer, (2) object-to-mouth transfer from mouthing of
pesticide-treated turfgrass, and (3) incidental ingestion of soil from
pesticide-treated residential areas. 

	

The exposure and risk estimates for the residential exposure scenarios
are assessed for the day of application (day “0") because it is
assumed that toddlers could contact the lawn immediately after
application. Risk from short-/intermediate-term incidental ingestion by
toddlers is assessed by comparing these exposures to the NOAEL of 100
mg/kg/day.  The results of the exposure calculations are summarized in
Table 6.2.

Table 5.2  Short-/Intermediate-Term Incidental Ingestion Exposure and
Risk

Scenarios	

TTR/GR/SR0

(ug/cm2 or g)	Short-/Int-Term

PDR0-norm

(mg/kg/day)	

Short-/Int-term

MOE

(1) Hand-to- Mouth 1	0.26	0.0070	14,000

(2) Object-to-Mouth 2	1.1	0.0018	57,000

(3) Soil Ingestion	3.5	0.000024	4,300,000

Total	N/A	0.0088	11,000

1 Estimate of percent of ae initially available based on default
assumption of 5% of application rate.

2 Estimate of percent of ae initially available based on default
assumption of 20% of application rate.

The short-/intermediate-term MOE for each scenario, and the combined
MOEs resulting from all three exposures, are above the LOC of 100,
regardless of whether the chemical-specific TTR data or a default
residue assumption was used, and therefore, are not of concern.

These exposure estimates are based on some upper-percentile and central
tendency assumptions and are considered to be representative of high-end
exposures.  The uncertainties associated with this assessment stem from
the use of an assumed amount of pesticide available from turf, and
assumptions regarding transfer of chemical residues and hand-to mouth
activity.  The estimated exposures are believed to be reasonable
high-end estimates based on observations from chemical-specific field
studies and professional judgment.

Recreational Post-Application Exposure and Risk			

Recreational exposures to turf are expected to be similar to, or in many
cases less than, those evaluated above; therefore, a separate
recreational exposure assessment was not included.  Although fluroxypyr
may be applied to golf courses, a risk assessment for the golfing
scenario is not required because a dermal endpoint was not selected.

Off Target Non-Occupational Exposure

Spray drift is always a potential source of exposure to residents nearby
to spraying operations.  This is particularly the case with aerial
application, but, to a lesser extent, could also be a potential source
of exposure from the ground application method employed for fluroxypyr. 
The Agency has been working with the Spray Drift Task Force, EPA
Regional Offices and State Lead Agencies for pesticide regulation and
other parties to develop the best spray drift management practices.  The
Agency is now requiring interim mitigation measures for aerial
applications that must be placed on product labels/labeling.  The Agency
has completed its evaluation of the new data base submitted by the Spray
Drift Task Force, a membership of U.S. pesticide registrants, and is
developing a policy on how to appropriately apply the data and the
AgDRIFT computer model to its risk assessments for pesticides applied by
air, orchard airblast and ground hydraulic methods.  After the policy is
in place, the Agency may impose further refinements in spray drift
management practices to reduce off-target drift and risks associated
with aerial as well as other application types where appropriate.  

Please note that, as indicated in this assessment, fluroxypyr is
directly applied to residential turf and does not result in exposures of
concern.  It is unlikely that the potential for risk of exposure to
spray drift from agricultural uses would be higher than that estimated
for the turf use of this chemical.

 TC \l2 "6.3	Other (Spray Drift, etc.) 

6.0	Aggregate Risk Assessments and Risk Characterization  TC \l1 "7.0
Aggregate Risk Assessments and Risk Characterization 

6.1	Acute Aggregate Risk

 TC \l2 "7.1	Acute Aggregate Risk 

  SEQ CHAPTER \h \r 1 No study was selected for the acute dietary
endpoint because an appropriate endpoint attributable to a single
exposure was not available in the oral studies; therefore, an acute
aggregate risk assessment was not conducted.

6.2	Short-Term and Intermediate Term Aggregate Risk

Since the endpoints selected for short-term and intermediate-term risk
assessment are the same, a single aggregate assessment will address both
durations of exposure.

  SEQ CHAPTER \h \r 1 The short-/intermediate-term aggregate risk
assessment estimates risks likely to result from exposure to fluroxypyr
residues from food, drinking water, and residential pesticide uses. 
High-end estimates of residential exposure are used, while average
values are used for food and drinking water exposure (i.e. chronic
exposures).  Exposures are compared to the short- and intermediate-term
incidental oral NOAEL (100 mg/kg/day) to calculate an MOE.

A short/intermediate-term risk assessment is required for adults because
there is a residential handler inhalation exposure scenario.  In
addition, a short-/intermediate-term risk assessment is required for
infants and children because there is a residential post-application
oral exposure scenario for infants and children.  As no short-/
intermediate-term dermal endpoint was established, there is no dermal
component to this aggregate risk assessment.

In conducting the short- and intermediate-term aggregate risk
assessments, HED made the following conservative assumptions.

Since the subgroup “U.S. Population” includes both children and
adults, HED included both incidental oral exposure and inhalation
exposures for residential handlers into the aggregate scenario for that
population.  

Incidental oral exposure from treated areas was included in the
aggregate scenarios for infants and children through age 12.

Inhalation exposure resulting from residential application was included
for youth age 13 through 19 years old as well as all adult subgroups.

Results of the short- and intermediate-term aggregate risk assessment
are summarized in Table 6.2 below.  Short- and intermediate-term
aggregate MOEs ranged from 4,400 to 54,000.  The MOE for the U.S.
Population is 8,300.  The most highly exposed subgroup was Children, 1-
2 years old, with an MOE of 4,400.  Due to conservative assumptions
built into these risk estimates, this should be considered to be a
screening level risk assessment.



Table 6.2 Short-/Intermediate-Term Aggregate Risk

Population	LOC for Aggregate Risk1	Exposure Food & Water (mg/kg/day)
Exposure oral

(mg/kg/day)2	Exposure inhalation (mg/kg/day)3	Aggregate MOE (food and
residential)4

U.S. Population (total)	100	

0.003253	0.0088	5.4E-05	8,300

All Infants (< 1 year old)

0.004834	0.0088	0	7,300

Children 1-2 years old

0.013865	0.0088	0	4,400

Children 3-5 years old

0.009828	0.0088	0	5,400

Children 6-12 years old 

0.006044	0.0088	0	6,700

Youth 13-19 years old

0.002901	0	5.4E-05	34,000

Adults 20-49 years old

0.002027	0	5.4E-05	48,000

Females 13-49 years old

0.001992	0	5.4E-05	49,000

Adults 50+ years old

0.001805	0	5.4E-05	54,000

1 LOC=100=10x for interspecies variability*10x for intraspecies
variability.

2 Incidental oral exposure applied to infants, and children through 12
years.  Incidental oral exposure also included in general population
assessment.

3Inhalation exposure included for general population, youth and adult
populations.

4 Aggregate MOE (food, water and residential) = ST NOAEL
(100mg/kg/day)/(food/water exposure + inhalation exposure + incidental
oral exposure)

6.3	Long-Term/Chronic Aggregate Risk TC \l2 "7.4	Long-Term Aggregate
Risk 

  SEQ CHAPTER \h \r 1 The long-term/chronic aggregate risk assessment
takes into account average exposure estimates from dietary consumption
of fluroxypyr (food and drinking water) and residential uses.  Based on
the fluroxypyr use pattern, no long-term residential exposures are
expected.  Therefore, the 

long-term aggregate risk assessment is based on exposure from food and
drinking water only.  

The Tier 1 chronic dietary exposure assessment was conducted for the
general U.S. population and various population subgroups assuming
tolerance level residues, 100% crop treated for all commodities, and
default DEEMTM (version 7.76) concentration factors.  The drinking water
estimated environmental concentration (EEC) for surface water of 3.3 ppb
was included directly in the DEEM analysis.  

The existing and proposed uses (food only) result in a long-term
aggregate exposure (food and water) to the U.S populations which is <1%
of the cPAD.  The most highly exposed subpopulation is children 1-2
years of age with an aggregate exposure (food and water) equivalent to
1.4% of the cPAD.  Results of the analysis are summarized in Table 6.3.

Table 6.3  Chronic Aggregate Risk Assessment for Fluroxypyr* 

Population Subgroup	Chronic Dietary

	

Exposure (mg/kg/day)	

% cPAD

U.S. Population (total)	

0.003253	

<1

All Infants (< 1 year old)	

0.004834	

<1

Children 1-2 years old	

0.013865	

1.4

Children 3-5 years old	

0.009828	

1.0

Children 6-12 years old	

0.006044	

<1

Youth 13-19 years old	

0.002901	

<1

Adults 20-49 years old	

0.002027	

<1

Females 13-49 years old	

0.001992	

<1

Adults 50+ years old	

0.001805	

<1

*This assessment represents risk from exposure through food and drinking
water sources.

 TC \l2 "7.5	Cancer Risk 

7.0	Cumulative Risk Characterization/Assessment  TC \l1 "8.0	Cumulative
Risk Characterization/Assessment 

Unlike other pesticides for which EPA has followed a cumulative risk
approach based on a common mechanism of toxicity, EPA has not made a
common mechanism of toxicity finding for fluroxypyr and any other
substances, and fluroxypyr does not appear to produce a toxic metabolite
produced by other substances.  For the purposes of this tolerance
action, therefore, EPA has not assumed that fluroxypyr has a common
mechanism of toxicity with other substances.  For information regarding
EPA’s efforts to determine which chemicals have a common mechanism of
toxicity and to evaluate the cumulative effects of such chemicals, see
the policy statements released by EPA’s OPP concerning common
mechanism determinations and procedures for cumulating effects from
substances found to have a common mechanism on EPA’s website at    
HYPERLINK "http://www.epa.gov/pesticides/cumulative/." 
http://www.epa.gov/pesticides/cumulative/. 

8.0	Occupational Exposure/Risk Pathway  TC \l1 "9.0	Occupational
Exposure/Risk Pathway 

8.1	Short-/Intermediate-/Long-Term Handler Risk  TC \l2 "9.1
Short-/Intermediate-/Long-Term/Cancer (if needed) Handler Risk 

There is a potential for exposure to fluroxypyr during mixing, loading,
and application activities associated with agricultural crops, as well
as turfgrass at residential and recreational sites.  An exposure/risk
assessment using applicable endpoints selected by the HIARC was
performed.  No chemical-specific handler exposure data were submitted in
support of this Section 3 registration.  In accordance with HED’s
Exposure Science Advisory Council (ExpoSAC) policy, exposure data from
the Pesticide Handlers Exposure Database (PHED) Version 1.1 as presented
in PHED Surrogate Exposure Guide (8/98) were used with other HED default
values for acres treated per day, body weight, and the level of personal
protective equipment to assess handler exposures.  

Handler’s exposure and risk were estimated for the following
scenarios:  (1) mixing/loading liquids for aerial application, (2)
mixing/loading liquids for groundboom application, (3) applying sprays
with fixed-wing aircraft, (4) applying sprays with a groundboom sprayer,
and (5) flagging sprays for aerial operations. 

As mentioned previously, a dermal endpoint was not selected; therefore,
the occupational risk assessment was based on inhalation exposure only. 
While an oral dose was selected, absorption via the inhalation route is
presumed to be comparable to oral absorption.

The MOEs range from 67,000 for mixing/loading liquids for aerial
application to 1,200,000 for flagging for aerial sprays.  These MOEs are
above the LOC of 100, and therefore, are not of concern.  The minimum
level of PPE for handlers is based on acute toxicity for the end-use
products.  RD is responsible for ensuring that PPE listed on the label
is in compliance with the Worker Protection Standard (WPS).  Exposure
assumptions and estimates for occupational handlers are summarized in
Table 8.1.		



Table 8.1  Inhalation Exposure and Risk Assessment for Occupational
Handlers

Exposure Scenario

	Inhalation

Unit Exposure 1 (mg/lb ae)	Crop

	Application Rate 2

(lb ae/A)	Area Treated 3

(A/day)	Daily 

Dose 4 (mg/kg/day)	Short-/Int-Term Inhalation

B*

…

»

¼

à

á

õ

ö

×

Ø

ì

í

 

-

L

n

o

ƒ

¼

Þ

ß

à

㄀$

j;

j¸

j¬

j/

j

 hØ

萏ː萑ﴰ␱䀀Ħ葞ː葠ﴰ

&

&

 h?

  h?

&

㐀ۖĀ̊d搃昀Ĵ

愀Ĥ

㐀ۖĀ̊d搃昀Ĵ

愀Ĥ

㐀ۖĀ̊d搃昀Ĵ

㐀ۖĀ̊d搃昀Ĵጀ

␱䀀Ħ

ˆÿò

$

@

$

@

@

@

@

㄀$

옍)

愀Ĥ

愀Ĥ

愀Ĥ

愀Ĥ

愀Ĥ

愀Ĥ

愀Ĥ

愀Ĥ

愀Ĥ

㜀$␸䠀$

h

ˆÿò

&

␱䀀&

愀Ĥሀ1. Mixing/Loading Liquids for Aerial Application	0.0012	dry bulb
onions,

garlic,

shallots	0.25	350	0.0015	67,000

2. Mixing/Loading Liquids for Groundboom Application

80	0.00034	290,000

3. Applying Sprays with Fixed-wing Aircraft (enclosed cockpit)	0.000068

	350	0.000085	1,200,000

4. Applying Sprays with a Groundboom Sprayer (open cab)	0.00074

	80	0.00021	470,000

5. Flagging (Sprays) for Aerial Operations	0.00035

	350	0.00044	230,000

1Unit Exposure values are based on exposure without a respirator. 
Values obtained from PHED Surrogate Exposure Guide. There is high
confidence in all values except for that of aerial application with an
enclosed-cockpit aircraft, for which there is medium confidence.

2 Maximum application rates were used for screening purposes.

3 Standard values for acres treated in a day were used. 

4 Daily Dose = [Unit Exposure (mg/lb ai handled) x Application Rate (lb
ae/A) x Acres Treated (A/day)] / Body Weight (70 kg)

5 MOE = NOAEL/ Daily Inhalation Dose.  Short-/Intermediate-term
Inhalation NOAEL = 100 mg/kg/day. 

8.2	Post-Application Risk  TC \l2 "9.2
Short-/Intermediate-/Long-Term/Cancer (if needed) Postapplication Risk 

This action on fluroxypyr involves foliar applications.  Therefore,
there is a potential for post-application exposure to scouts, harvesters
and other field and maintenance workers.  However, because no
appropriate dermal endpoints were identified for this exposure
potential, and post-application inhalation exposure is expected to be
negligible, an occupational post-application risk assessment was not
conducted.  

REI

 Starane™ label has a 12-hour REI, which complies with the WPS

9.0	Data Needs and Label Requirements

9.1	Toxicology

No additional toxicology data are required to support the requested use
on dry bulb onions.

9.2	Residue Chemistry

Provided a label for the Starane™ is submitted which reflects the use
directions specified in the administrative volume contained in this
petition, and the identified deficiencies stated below are addressed as
conditions of the registration, there are no major residue chemistry
issues which would preclude the establishment of a permanent tolerance
for fluroxypyr in/on dry bulb onions (including garlic and shallots). 
Deficiencies which should be addressed as a condition of registration
are as follows:

IR-4 must develop a confirmatory analytical method for the determination
of fluroxypyr residues, as required for enforcement methods.  Further,
the petitioner should revise the current analytical method, GRM 96.02 to
reflect dry bulb onion specific changes and submit that method to FDA
for inclusion in PAM II as the tolerance enforcement method.

A metabolism study is required to elucidate the nature of the residue in
bulb onions.

9.3	Occupational/Residential Exposure

No additional occupational/residential exposure data are required to
support the requested use on dry bulb onions (including garlic and
shallots).

References

Hazard Assessment 

FLUROXYPYR - SECOND Report of the Hazard Identification Assessment
Review Committee -TXR. No. 0051987, 06/26/2003. 

Residue Chemistry Assessment

Fluroxypyr:  Petition for Tolerance to Support Use on Dry Bulb Onions,
Including Garlic and Shallots.  Summary of Analytical Chemistry and
Residue Data. Petition Number: 3E6775 D331225. D. Davis. 8/2/06. 

Dietary Exposure Analysis

Fluroxypyr Chronic Dietary Exposure and Risk Assessment for Requests for
Tolerances for Residues in/on Onion, Dry Bulb, Garlic and Shallot. A.
Acierto. D328732. 08/01/06.  

Occupational and Residential Exposure Assessment

옍)

옍)

옍)

ༀꂄᄅ悄ㇺ$葞֠葠褐ༀ Support Request for a Section 3
Registration of Fluroxypyr on Corn, Sorghum, Rangeland and Permanent
Grass Pastures, and Turf. K. O’Rourke, D285872, 8/28/03

Drinking Water Assessment

Drinking Water Assessment for fluroxypyr use on rangeland and permanent
grass pastures. I. Abdel-Saheb, D292471, 8/13/03.

  TC \l2 "10.2	Residue Chemistry 

Fluroxypyr        Dry Bulb Onion Human Health Risk Assessment           
     D314019

Page   PAGE  28  of   NUMPAGES  28 

Page   PAGE  1  of   NUMPAGES  28 

Page   PAGE  29  of   NUMPAGES  25