Document ID: EPA-HQ-OPP-2007-0309-0005
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-12-26T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM

Date:		15-AUG-2007

Subject:	PP# 6E7150.  Etoxazole.  Registration for Use on Cherries,
Hops, and Melon Subgroup 9A.  Summary of Analytical Chemistry and
Residue Data.

DP#:  		335334		Decision#:  330258		

PC Code:	107091		MRID#: 470036-01 thru 470036-03

40 CFR:		180.593		Chemical Class:  unclassified acaricide

From:		Jennifer R. Tyler, Chemist

Sarah J. Levy, Chemist

Registration Action Branch (RAB1)

Health Effects Division (HED; 7509P)

Through:	George F. Kramer, Ph.D., Senior Chemist

RAB/HED (7509P)

To:		Sidney Jackson/Daniel Rosenblatt, PM Team 05

Registration Division (RD, 7505P)

Executive Summary

Etoxazole
[2-(2,6-difluorophenyl)-4-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5-dih
ydrooxazole] is a contact acaricide/ovicide that is currently registered
in the United States (U.S.) for the control of mites on various raw
agricultural commodities (RACs).  Permanent tolerances have been
established for residues of etoxazole in/on plant commodities, ranging
from 0.05 ppm for cottonseed to 1.0 ppm for cotton gin byproducts [40
CFR §180.593(a)].  Tolerances have also been established for etoxazole
residues in fat (0.02 ppm) and liver (0.01 ppm) of ruminants and in milk
fat (0.01 ppm).

The Interregional Research Project Number 4 (IR-4) has submitted a
petition (PP# 6E7150) proposing uses for etoxazole, formulated as Zeal®
Wettable Powder (WP; EPA Reg. No. 59639-123) and Secure® WP (EPA Reg.
No. 59639-138) on cherries, hops, and melon subgroup 9A.  The petitioner
has proposed the establishment of permanent tolerances for etoxazole
residues of 0.70 ppm in/on cherries; 7.0 ppm in/on hop, dried cones; and
1.5 ppm in/on melon, subgroup 9A.

The qualitative nature of etoxazole residues in plants is understood
based upon the plant metabolism studies on cotton, eggplant, apple and
orange.  In plants, etoxazole may undergo photo-oxidation to yield
Metabolite R-13.  Parent and Metabolite R-13 then undergo opening of the
oxazole ring to form a variety of metabolites (R-4, R-7, R-14, and R-3),
and subsequent cleavage of the opened ring forms Metabolites DFB, R-8,
R-10, R-11, R-12, and R-15.The HED Metabolism Assessment Review
Committee (MARC, 4/23/03) concluded that only parent should be included
in the tolerance expression for all plant commodities.  For risk
assessment purposes, only parent will be considered for most plant
commodities; however, Metabolite R-3 should also be included in the risk
assessment for cotton gin byproducts and almond hulls.  

In the crop field trials submitted with the current petition, residues
of etoxazole were determined using modifications of previously submitted
gas chromatography (GC) with nitrogen-phosphorus detector (NPD) or
mass-selective detector (MSD) methods (Methods RM-37, or RM-37HM). 
These methods have been reviewed by HED and deemed adequate for data
collection.  The methods and any modifications were also adequately
validated in conjunction with the sample analyses.  In addition, the
current tolerance enforcement methods are adequate for enforcing the
proposed tolerances on the proposed tolerances.  The aforementioned
methods were forwarded to the Analytical Chemistry Laboratory (ACL) for
Agency petition method validations (PMVs) (Memos, J. Tyler, 6/17/03;
D290912 and D290914).

Food and Drug Administration (FDA) multiresidue methods (MRMs) may be
used to determine residues of etoxazole in fatty and non-fatty matrices
and to determine residues of Metabolite R-3 in nonfatty matrices. 
Etoxazole was completely recovered from fortified samples of apple using
Methods 302, E1 with GC/NPD or Method 303, C1 or C2 with GC/NPD. 
Etoxazole was partially recovered from cottonseeds (fatty matrix) using
Method 304, E5, C1 or C2 with GC/NPD.  Metabolite R-3 could be
completely recovered from cotton gin byproducts using Method 302, E4
using GC/NPD.  However, matrix interferences enhanced the recoveries of
R-3 from gin byproducts.  The results of the MRM testing were forwarded
to the FDA for inclusion in the Pesticide Analytical Method (PAM) Vol. I
(Memo, J. Tyler, 6/17/03; D290919).

Adequate storage stability data are available to support the current
magnitude of the residue and processing studies.  The available hop
storage stability data are adequate to support crop field trial data. 
For cherries and cantaloupe, adequate storage stability data are
available; however, residue values were corrected in order to correct
for storage dissipation (64% and 67% for cherries and cantaloupe,
respectively).

The submitted cherry field trial data reflect a total of 2 foliar
applications of etoxazole (Zeal® 72 WDG) on tart and sweet cherries at
a rate of 0.135 pounds (lb) active ingredient (ai)/acre (A)/application
for a total application rate of 0.27 lb ai/A [2x the maximum proposed
seasonal application rate; preharvest interval (PHI)=7 days].  The
results show that corrected residues of etoxazole (corrected for storage
dissipation) in tart and sweet pitted cherries were 0.31-1.2 ppm and
0.13-0.28 ppm, respectively.

The submitted cantaloupe field trial data reflect a total of 2 foliar
applications of etoxazole (Zeal® 72 WDG) on cantaloupes at a rate of
0.135 lb ai/A/application for a total application rate of 0.27 lb ai/A
(2x the maximum proposed seasonal application rate; PHI=5-8 days).  The
results show that residues of etoxazole (corrected for storage
dissipation) in cantaloupe were 0.016-0.12 ppm.

The submitted hop field trial data reflect a total of 2 foliar
applications of etoxazole (Zeal® 72 WDG) on hops at a rate of 0.198 lb
ai/A, for at total application rate of approximately 0.396 lb ai/A (~3x
the maximum proposed seasonal application rate; PHI=6-7 days).  The
results show that residues of etoxazole in dried hop cones were
1.98-4.18 ppm.

The application rates used in the cherry (2 applications at 0.135 lb
ai/A/application for a total application rate of 0.27 lb ai/A),
cantaloupe (2 applications at 0.135 lb ai/A/application for a total
application rate of 0.27 lb ai/A), and hop field trials (2 applications
at 0.198 lb ai/A/application for a total application rate of 0.396 lb
ai/A) do not match the proposed application rates (1 application at
0.135 lb ai/A for cherry and melon; 1 application at 0.180 lb ai/A for
hops).  However, as the residue decline data show that residues decrease
in cherries and cantaloupe with increasing PHIs, the majority of the
residues seen the field trials would most likely be due to the second
application.  Therefore, potential residues of etoxazole in/on cherries
and cantaloupe will not be underestimated.  Based on the highest-average
field trial (HAFT) residues in cherries and cantaloupe the residue data
are adequate to support tolerances for cherry, tart (0.60 ppm); cherry,
sweet (0.20 ppm); and vegetable, cucurbit subgroup 9A (0.15 ppm).  For
hops, the available residue decline data show that residues of etoxazole
do not decrease significantly in dried hop cones with increasing PHIs. 
Based on the HAFT residue of 4.14 ppm, the available data are adequate
to support a conditional registration and a permanent tolerance of 5.0
ppm on hop, dried cones.  The registration should be made unconditional
upon submission of additional side-by-side data as follows:  1 trial
each at 2 x 0.198 = 0.396 lb ai/A (exaggerated application rate, PHI = 7
days) and one at 0.180 lb ai/A (proposed application rate, PHI = 7
days), 4 samples per trial.  As R3 is a metabolite of concern in cotton
gin byproducts, and a metabolism data are not available for hops, R3 is
a potential residue of concern for this crop.  Therefore, the requested
side-by-side hop field trial should include data for R3, as well as the
parent.  Subsequent to the submission of these data, RAB1 will make a
determination as to whether or not R3 is a residue of concern in hops.

There are no rotational crop restrictions on the proposed labels.  HED
concluded that, based on the available confined rotational crop data, no
rotational crop restrictions would be required for rotational crops
following applications at rates totaling 0.135 lb ai/A/season, which is
the maximum proposed application rate for cantaloupe (the only proposed
use that is considered to be a rotated crop).  Therefore, the available
rotational crop data are adequate to support the proposed uses.

There are no established or proposed Codex, Canadian or Mexican maximum
residue limits (MRLs) for etoxazole; therefore, harmonization is not an
issue for this action.



Residue Chemistry Deficiencies

Revised Section F.

Additional residue data on hops as follows:  1 trial each at 2 x 0.198 =
0.396 lb ai/A (exaggerated application rate, PHI = 7 days) and one at
0.180 lb ai/A (proposed application rate, PHI = 7 days), 4 samples per
trial.  As R3 is a metabolite of concern in cotton gin byproducts, and a
metabolism data are not available for hops, R3 is a potential residue of
concern for this crop.  Therefore, the requested side-by-side hop field
trial should include data for R3, as well as the parent.  Subsequent to
the submission of these data, RAB1 will make a determination as to
whether or not R3 is a residue of concern in hops.

Recommendations

Provided a revised Section F is submitted and successful Agency PMVs of
the analytical enforcement methods are reported, the available residue
chemistry data support the establishment of the following:

Unconditional registration and permanent tolerances for residues of
etoxazole per se in/on the following RACs:  cherry, sweet (0.60 ppm);
cherry, tart (0.20 ppm); and vegetable, cucurbit subgroup 9A (0.15 ppm).

Conditional registration and permanent tolerance for residues of
etoxazole per se in/on hop, dried, cone at 5.0 ppm.  The registration
should be made unconditional upon submission of additional residue data
as specified above.

A human-health risk assessment is forthcoming.

Background

Etoxazole is a contact acaricide/ovicide used for the control of
tetranychid mite species.  It is currently registered for use on cotton,
pome fruits, and strawberries.  Permanent tolerances have been
established for residues of etoxazole in/on plant commodities, ranging
from 0.05 ppm in cottonseed to 1.0 ppm in cotton gin byproducts [40 CFR
§180.593(a)].  Tolerances have also been established for etoxazole
residues in fat (0.02 ppm) and liver (0.01 ppm) of ruminants and in milk
fat (0.01 ppm).

sing uses for etoxazole, formulated as Zeal™ WP Miticide and Secure(
Miticide , in the U.S. on cherries, hops, and melon subgroup 9A.  In
conjunction with these uses, the petitioner has proposing the
establishment of permanent tolerances for etoxazole residues in/on the
following plant RACs:  cherry at 0.70 ppm; hop, dried cones at 7.0 ppm;
and melon, subgroup 9A at 0.15 ppm.  The nomenclature and
physicochemical properties of etoxazole are presented below in Tables 1
and 2.



 

Common name	Etoxazole

Company experimental names	S-1283, V-1283, YI-5301

IUPAC name
(RS)-5-tert-butyl-2-[2-(2,6-difluorophenyl)-4,5-dihydro-1,3-oxazol-4-yl]
phenetole

CAS name
2-(2,6-difluorophenyl)-4-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5-dihy
drooxazole

CAS #	153233-91-1

End-use products/EP	72% WDG (Zeal® WP Miticide and Secure™ Miticide)

Table 2.	Physicochemical Properties of Etoxazole (TGAI)

Parameter	Value	References

Melting range	101.5-102.5(C	46018505.der.wpd

pH	6.2

	Density	1.2389 g/cm3

	Water solubility 	3.99 x 10-5 at 10(C

7.04 x 10-5 at 20(C

6.69 x 10-5 at 30(C

	Solvent solubility (g/L at 20(C)	acetone: 309		1,2-dichloroethane: 402

ethyl acetate: 249		n-heptane: 18.7

methanol: 104		xylene: 252

	Vapor pressure at 25(C	7.0 x 10-6 pascals

	Dissociation constant (pKa)	no measurable pKa

	Octanol/water partition coefficient Log(KOW)	5.52 ± 0.58 at 20(C

	UV/visible absorption	Not available.

	

860.1200 Directions for Use

Table 3.  Summary of Proposed Directions for Use of Etoxazole.

Application, Timing, Type, and Equipment	Formulation

(EPA Reg. No.)	Application Rate

(lb ai/A)	Maximum Number Applications/Season	RTI (days) 1	PHI

™ Miticide (59639-123)	0.09-0.135	0.135	1	-	7	A minimum application
volume of 50 gallon/A is recommended.

	Zeal® WP Miticide (59639-138)	0.09-0.135	0.135	1	-	7	A minimum
application volume of 50 gallon/A is recommended.

Hops

Broadcast foliar application; ground equipment.	Secure™ Miticide
(59639-123)	0.135-0.18	0.18	1	-	7	A minimum application volume of 50
gallon/A is recommended.

	Zeal® WP Miticide (59639-138)	0.135-0.18	0.18	1	-	7	A minimum
application volume of 50 gallon/A is recommended.

Melon Subgroup 9A

Broadcast foliar application; ground equipment.	Secure™ Miticide
(59639-123)	0.09-0.135	0.135	1	-	7	A minimum application volume of 50
gallon/A is recommended.

	Zeal® WP Miticide (59639-138)	0.09-0.135	0.135	1	-	7	A minimum
application volume of 50 gallon/A is recommended.

1.  RTI = minimum retreatment interval; PHI = minimum preharvest
interval.

2.  The proposed label does not include any rotational crop
restrictions.

HED Conclusions.  Although the submitted cherry, cantaloupe, and hop
crop field trials were conducted at exaggerated rates (~2-3x), HED
concludes that the data are adequate to support the proposed uses. 
However, the registration on hops should be conditional until additional
crop field trial data are submitted.

860.1300 Nature of the Residue - Plants

The qualitative nature of etoxazole residues in plants is understood
based upon the plant metabolism studies on cotton, eggplant, apple and
orange.  In each of the studies, the major 14C-residue in/on various
matrices was identified as parent compound.  Based on the metabolite
profiles observed in these studies, etoxazole may undergo
photo-oxidation to yield Metabolite R-13.  Parent and Metabolite R-13
then undergo opening of the oxazole ring to form a variety of
metabolites (R-4, R-7, R-14, and R-3), and subsequent cleavage of the
opened ring forms Metabolites DFB, R-8, R-10, R-11, R-12, and R-15.

Based on the above studies, the MARC (Memo, J. Tyler, 6/17/03; D289666)
concluded that parent is the only residue of concern in plant
commodities for purposes of the tolerance expression and risk
assessment.  However, for cotton gin byproducts, the risk assessment
should also include Metabolite R-3.  In addition, based on the results
of the crop field trial on almonds, HED has determined that Metabolite
R-3 should also be included in the risk assessment for almond hulls
(Memo, J. Tyler, 3/30/05; D303628).

860.1340 Residue Analytical Methods

Adequate methods are available for enforcing the current plant and
livestock tolerances.  In the current trials and processing study,
samples were analyzed using either the proposed enforcement methods or a
slightly modified version of current enforcement methods.

The GC/MSD method used to analyze etoxazole residues in/on cherry
samples in the crop field trial study is a slightly modified version of
a previously-validated method (Method RM-37HM).  The method was
adequately validated in conjunction with the sample analyses.  The
validated LOQ was 0.0037 ppm and the LOD was 0.0012 ppm for etoxazole
in/on cherries.

The GC/NPD methods used to analyze etoxazole residues in/on cantaloupe
fruit and dried hop cones in the respective crop field trials are
slightly modified version of a previously-validated method (Method
RM-37).  The method was adequately validated in conjunction with the
sample analyses.  The validated LOQs were 0.0046 ppm and 0.2 ppm for
cantaloupe and hops, respectively; and the validated LODs were 0.0015
ppm and 0.1 ppm for etoxazole in/on cantaloupe and hops, respectively.

HED Conclusions.  The GC/NPD or MSD methods used in the submitted field
trials are adequate for determining residues of etoxazole in cherries,
cantaloupe, and hops.  The current tolerance enforcement methods are
also adequate for enforcing the proposed tolerances given the similarity
between these commodities and the plant commodities with established
tolerances (cottonseed, apple, strawberry, and tangerine).  The
aforementioned methods were forwarded to the ACL for Agency PMVs (Memos,
J. Tyler, 6/17/03; D290912 and D290914).

860.1360 MRM

FDA MRMs may be used to determine residues of etoxazole in fatty and
non-fatty matrices and to determine residues of Metabolite R-3 in
nonfatty matrices.  Etoxazole was completely recovered from fortified
samples of apple using Methods 302, E1 with GC/NPD or Method 303, C1 or
C2 with GC/NPD.  Etoxazole was partially recovered from cottonseeds
(fatty matrix) using Method 304, E5, C1 or C2 with GC/NPD.  Metabolite
R-3 could be completely recovered from cotton gin byproducts using
Method 302, E4 using GC/NPD.  However, matrix interferences enhanced the
recoveries of R-3 from gin byproducts. The results of the MRM testing
were forwarded to the FDA for inclusion in the PAM Vol. I (Memo, J.
Tyler, 6/17/03; D290919).

860.1380 Storage Stability

The maximum storage intervals for treated samples in the cherry,
cantaloupe, and hop crop field trial studies were 179, 72, and 60 days,
respectively.  Previously-submitted storage stability data (Memo, J.
Tyler, 7/17/03; D283737) indicate that etoxazole is stable at -20(C for
at least 3.5 months in apples, 2 months in strawberries, 6 months in
orange pulp, 12 months in orange peels, 17 months in cottonseed, and 6
months in cotton gin byproducts.  Additional storage stability data
conducted in conjunction with the current cherry, cantaloupe, and hop
field trials were submitted.  In the cherry crop field trial study,
samples fortified with 0.10 ppm and analyzed a 193 days had an average
recovery of 64%.  In the cantaloupe crop field trial study, samples
fortified with 0.10 ppm and analyzed at 50 and 126 days had average
corrected recoveries of 64% and 70%, respectively.  In the hops crop
field trial study, samples fortified with 0.10 ppm and analyzed at 84
days had an average corrected recovery of 101%.

HED Conclusions:  The available hop storage stability data are adequate
to support crop field trial data.  For cherries and cantaloupe, adequate
storage stability data are available; however, residue values were
corrected in order to correct for storage dissipation (64% and 67% for
cherries and cantaloupe, respectively). 

860.1480 Meat, Milk, Poultry, and Eggs

There are no livestock feed commodities associated with the proposed
uses.

860.1500 Crop Field Trials

47003601.der  (cherries)

47003602.der (cantaloupe)

47003603.der (hops)

IR-4 has submitted cherry, cantaloupe and hop field trial data
supporting the proposed uses of etoxazole.  The results from the
currently reviewed field trials are discussed below and summarized in
Table 4.

Table 4.	Summary of Residues from the Crop Field Trials with Etoxazole.

Crop Matrix	Application Rate

(lb ai/A)

[g ai/A]	PHI (days)1	Etoxazole Residues (ppm) 2

	N	Min	Max.	HAFT3	Mean	Std. Dev.

Cherries (proposed use = 0.135 lb ai/A total application rate, 7-day
PHI)

Tart Cherry4	0.271-0.297	6-8	14	0.31	1.2	0.88	0.48	0.23

Sweet Cherry4	0.272-0.2897	6-8	12	0.13	0.28	0.29	0.20	0.050

Melon Subgroup 9A (proposed use = 0.135 lb ai/A total application rate,
7-day PHI)

Cantaloupe fruit4	0.264-0.278	5-8	18	0.016	0.12	0.12	0.042	0.027

Hops (proposed use = 0.18 lb ai/A total application rate, 7-day PHI)

Dried hop cones	0.3620.396

[165.7-181.4]	6-7	6	1.98	4.18	3.96	3.45	0.96

1.  PHI = preharvest interval.

2.  The LOQs are 0.0037 ppm, 0.0046 ppm, and 0.2 ppm in/on cherries,
cantaloupe and hops, respectively; the LOD was 0.0012 ppm, 0.0015 ppm,
0.1 ppm on cherries, cantaloupe, and hops, respectively.

3.  HAFT = highest-average field trial.

4.  Corrected residue values to account for storage dissipation were
used to determine residue summary information.

Cherries:  IR-4 has submitted field trial data for etoxazole on
cherries.  A total of thirteen (seven with tart cherries and six with
sweet cherries) were conducted in the United States during the 2004
growing season encompassing Regions 1 (NJ, n=1 tart), 5 (MI, n=6 – 4
tart and 2 sweet), 9 (CO, n=1 tart), 10 (CA, n=2 sweet), 11 (WA and ID,
n=2 – 1 tart and 1 sweet), and 12 (OR, n=1 sweet).

At each trial location, a total of 2 foliar-directed applications of
Zeal® 72 WDG, a water- dispersible granule formulation containing 72%
etoxazole as the ai, were applied at a rate of approximately 0.135 lb
ai/A/application (1x the maximum proposed single application rate) at
12- to 14-day retreatment intervals (RTIs) for a total application rate
of approximately 0.27 lb ai/A (2x the maximum proposed seasonal
application rate).  Samples were harvested 6-8 days following the second
application.  Additional samples were collected at the 04-WA13 and
04-MI16 at approximately 3, 7, and 14 days after the final application
in order to determine residue decline.  No spray additives were added to
the spray mixture.

Residues of etoxazole were 0.20-0.76 ppm in/on 14 tart cherry samples,
and 0.082-0.18 ppm in/on 12 sweet cherry samples harvested 6-8 days
following two foliar applications of etoxazole totaling ~0.27 lb ai/A. 
The results show that corrected residues of etoxazole (corrected for
storage dissipation) in tart and sweet pitted cherries were 0.31-1.2 ppm
and 0.13-0.28 ppm, respectively.  The highest-average field trial (HAFT)
residues of etoxazole in tart and sweet cherries were 0.56 ppm and 0.17
ppm, respectively.  The results of the decline trials indicate that
residues of etoxazole declined to a maximum of 0.25 ppm by 14 days in
tart cherries, and 0.096 ppm in sweet cherries.

Melon Subgroup 9A:  IR-4 has submitted field trial data for etoxazole on
cantaloupe.  A total of nine field trials were conducted in the United
States during the 2004 growing season encompassing Regions 2 (MD and GA,
n=2), 5 (WI, n=1), 6 (TX, n=2), and 10 (NM and CA, n=4).

At each trial location, a total of 2 broadcast foliar applications of
Zeal® 72 WDG, a water- dispersible granule formulation containing 72%
etoxazole as the ai, were applied at a rate of approximately 0.135 lb
ai/A/application (1x the maximum proposed single application rate) at
21-day RTIs for a total application rate of approximately 0.27 lb ai/A
(2x the maximum proposed seasonal application rate).  Samples were
harvested 5-8 days following the second application.  Additional samples
were collected at the 04-NM01 at approximately 3, 8, and 14 days after
the final application in order to determine residue decline.  No spray
additives were added to the spray mixture.

Residues of etoxazole were 0.016-0.12 ppm in/on 18 cantaloupe samples
harvested 5-8 days following two foliar applications of etoxazole
totaling ~0.27 lb ai/A.  The results show that residues of etoxazole
(corrected for storage dissipation) in cantaloupe were 0.016-0.12 ppm. 
The HAFT was 0.12 ppm.  The results of the decline trial indicate that
residues of etoxazole declined to a maximum of 0.010 ppm by 14 days.

Hops:  IR-4 has submitted field trial data for etoxazole on hops.  A
total of three field trials were conducted in the United States during
the 2003 growing season encompassing Regions11 (WA and ID, n=2), and 12
(OR, n=1).

At each trial location, a total of 2 foliar airblast applications of
Zeal™ 72 WDG, a water- dispersible granule formulation containing 72%
etoxazole as ai, were applied at a rate of approximately 0.198 lb ai/A
[90.7 grams (g) ai/A/application; ~1x the maximum proposed single
application rate], for at total application rate of approximately 0.396
lb ai/A (181.4 g ai/A; ~2x the maximum proposed seasonal application
rate).  For one trial, a second plot was treated with 2 foliar airblast
applications at 0.396 lb ai/A/application (181.4 g ai/A/application),
for a total application rate of 0.792 lb ai/A (362.8 g ai/A).  All
applications were made at 14- to 15-day RTIs, and hop cones were
harvested at commercial maturity, at 6- to 7-day PHIs.  Additional hop
samples were harvested at 2-, 6-, 13-, and 20-day PHIs from one trial
site to examine residue decline.  All samples were dried in commercial
driers after harvest.  A single control and duplicate treated samples
were collected from each trial.

Residues of etoxazole were 1.98-4.18 ppm in/on 6 dried hop cone samples
harvested 6-7 days following two foliar applications of etoxazole
totaling ~0.396 lb ai/A.  The results show that residues of etoxazole in
dried hop cones were 1.98-4.18 ppm.  The HAFT residue of etoxazole in
dried hop cones was 4.14 ppm.  Residue decline data show that residues
of etoxazole do not decrease significantly in dried hop cones with
increasing PHIs.

HED Conclusions.  For cherries, the crop field trial data are classified
as acceptable and satisfy the guideline requirement for crop field
trials (Residue Chemistry Guidelines OPPTS 860.1500). The location and
distribution of the field trials differ slightly from the recommended
distribution and locations.  A total of thirteen (seven with tart
cherries and six with sweet cherries) were conducted in Regions 1 (NJ,
n=1 tart), 5 (MI, n=6 – 4 tart and 2 sweet), 9 (CO, n=1 tart), 10 (CA,
n=2 sweet), 11 (WA and ID, n=2 – 1 tart and 1 sweet), and 12 (OR, n=1
sweet).  HED guidelines recommend Regions 1 (NJ, n=1 tart), 5 (MI, n=6
– 4 tart and 2 sweet), 9 (CO, n=1 tart), 10 (CA, n=2 sweet), and 11
(WA and ID, n=2 sweet).  However, the available data are adequate to
support the proposed use.

The submitted cherry field trial data reflect a total of 2 foliar
applications of etoxazole (Zeal® 72 WDG) on tart and sweet cherries at
a rate of 0.135 lb ai/A/application for a total application rate of 0.27
lb ai/A (2x the maximum proposed seasonal application rate; PHI=7 days).
 The results show that corrected residues of etoxazole (corrected for
storage dissipation) in tart and sweet pitted cherries were 0.31-1.2 ppm
and 0.13-0.28 ppm, respectively.  The results of the decline trials
indicate that residues of etoxazole declined to a maximum of 0.25 ppm by
14 days in tart cherries, and 0.096 ppm in sweet cherries.  The
application rates used in the field trials (2 applications at 0.135 lb
ai/A/application for a total application rate of 0.27 lb ai/A) does not
match the proposed application rate (1 application at 0.135 lb ai/A). 
As the residue decline data show that residues decrease in cherries with
increasing PHIs, the majority of the residues seen the field trials
would most likely be due to the second application.  Therefore,
potential residues of etoxazole in/on cherries will not be
underestimated.  Based on the HAFT residues of 0.56 ppm and 0.17 ppm in
tart and sweet cherries, respectively, the residue data are adequate to
support tolerances of 0.60 ppm and 0.20 ppm for residues of etoxazole on
cherry, tart and cherry, sweet.

For cantaloupe, the crop field trial data for cantaloupe are classified
as acceptable and satisfy the guideline requirement for crop field
trials (Residue Chemistry Guidelines OPPTS 860.1500).  The submitted
cantaloupe field trial data reflect a total of 2 foliar applications of
etoxazole (Zeal® 72 WDG) on cantaloupes at a rate of 0.135 lb
ai/A/application for a total application rate of 0.27 lb ai/A (2x the
maximum proposed seasonal application rate; PHI=5-8 days).  The results
show that residues of etoxazole (corrected for storage dissipation) in
cantaloupe were 0.016-0.12 ppm. The application rate used in the field
trials (2 applications at 0.135 lb ai/A/application for a total
application rate of 0.27 lb ai/A) does not match the proposed
application rate (1 application at 0.135 lb ai/A).  As the residue
decline data show that residues decrease in cantaloupe with increasing
PHIs, the majority of the residues seen the field trials would most
likely be due to the second application.  Therefore, potential residues
of etoxazole in/on the cucurbit crop subgroup will not be
underestimated.  Based on the HAFT residue of 0.12 ppm, the residue data
are adequate to support a tolerance of 0.15 ppm on vegetable, cucurbit
subgroup 9A.

The crop field trial data for hops are classified as acceptable and
satisfy the guideline requirement for crop field trials (Residue
Chemistry Guidelines OPPTS 860.1500).  The submitted hop field trial
data reflect a total of 2 foliar applications of etoxazole (Zeal® 72
WDG) on hops at a rate of 0.198 lb ai/A, for at total application rate
of approximately 0.396 lb ai/A (~3x the maximum proposed seasonal
application rate; PHI=6-7 days).  The results show that residues of
etoxazole in dried hop cones were 1.98-4.18 ppm.  The application rate
used in the field trials (2 applications at 0.198 lb ai/A/application
for a total application rate of 0.396 lb ai/A) does not match the
proposed application rate (1 application at 0.180 lb ai/A).  The
available residue decline data show that residues of etoxazole do not
decrease significantly in dried hop cones with increasing PHIs.  Based
on the HAFT residue of 4.14 ppm, the available data are adequate to
support a conditional registration and a tolerance of 5.0 ppm on hop,
dried cones.  The registration should be made unconditional upon
submission of additional side-by-side residue data as follows:  1 trial
each at 2 x 0.198 = 0.396 lb ai/A (exaggerated application rate, PHI = 7
days) and one at 0.180 lb ai/A (proposed application rate, PHI = 7
days), 4 samples per trial.  As R3 is a metabolite of concern in cotton
gin byproducts, and a metabolism data are not available for hops, R3 is
a potential residue of concern for this crop.  Therefore, the requested
side-by-side hop field trial should include data for R3, as well as the
parent.  Subsequent to the submission of these data, RAB1 will make a
determination as to whether or not R3 is a residue of concern in hops.

860.1520 Processed Food and Feed

As there are no processed commodities associated with the proposed uses,
processing studies are not required to support the subject petition.



860.1850/1900 Confined and Field Accumulation in Rotational Crops

Cantaloupes are the only rotated commodity associated with the proposed
uses.  The results of a confined rotational crop study was submitted and
reviewed by HED (Memo, J. Tyler, 7/31/03; D283737).  HED made the
following recommendation:

The submitted confined rotational crop study adequately depicts the
potential for accumulation of inadvertent etoxazole residues in
rotational crops following applications at rates totaling 0.1 lb
ai/A/season.  As TRR levels were <0.01 ppm in all rotational crop
commodities harvested from the ~30-day PBI, no rotational crop
restrictions would be required for rotational crops following
applications at rates totaling 0.1 lb ai/A/season.

In a separate memo dated 4/6/05, HED made the following recommendation 
(Memo, J. Tyler; D307178):

As mentioned above, the submitted confined rotational crop study
(45621724.der.wpd) adequately depicts the potential for accumulation of
inadvertent etoxazole residues in rotational crops following
applications at rates totaling 0.1 lb ai/A/season.  In that study, the
total radioactive residue (TRR) levels were <0.005 ppm in all rotational
crop commodities harvested from the ~30-day plantback interval (PBI).

The newly proposed application rate for strawberries (0.135 lb ai/A) is
slightly higher than the rate used in the confined rotational crop study
(0.1 lb ai/A).  However, all residues were <0.005 ppm in all rotational
commodities harvested from the 30-PBI following the 0.1 lb ai/A
application.  HED does not anticipate a significant increase in
inadvertent residues of etoxazole in crops when rotated with
strawberries treated with etoxazole at a seasonal rate of 0.135 lb ai/A.
 The current confined rotational crop study will support the strawberry
use; therefore, a new confined rotational crop study is no longer
warranted.  This deficiency has been resolved.

HED Conclusions:  There are no rotational crop restrictions on the
proposed labels.  HED concluded that, based on the available confined
rotational crop data, no rotational crop restrictions would be required
for rotational crops following applications at rates totaling 0.135 lb
ai/A/season, which is the maximum proposed application rate for
cantaloupe.  Therefore, the available rotational crop data are adequate
to support the proposed uses.

860.1550 Proposed Tolerances

A summary of the recommended tolerances and the correct commodity
definitions for the proposed uses are listed in Table 5.  As the
application rates used in the submitted crop field trials were 2-3x the
proposed application rates, the appropriate tolerance levels were
determined based on the respective HAFTs.  Provided revised Section F is
submitted as specified, the residue chemistry database supports the
establishment of permanent tolerances for residues of etoxazole in/on
the RACs listed in Table 5.



Table 5.  Tolerance Summary for Etoxazole

Commodity	Proposed Tolerance (ppm)	Recommended Tolerance (ppm)	Comments

(Correct commodity definition)

Cherry	0.70	0.60	Cherry, sweet

0.20	Cherry, tart

Hop, dried cones	7.0	5.0

	Melon subgroup 9A	0.15	0.15	Vegetable, cucurbit subgroup 9A

International Tolerances

There are no established or proposed Codex, Canadian or Mexican MRLs for
etoxazole; therefore, harmonization is not an issue for this action [see
attached International Residue Limit Status (IRLS) Sheet].

References

DP Barcode:	D290919

Subject:	PP#2F6420.  Multiresidue Method (MRM) Testing of Etoxazole.

From:		J. Tyler

To:		C. Stafford

Dated:		6/17/2003

MRID(s):	45621825

DP Barcode:	D289666

Subject:	Etoxazole:  Health Effects Division (HED) Metabolism Assessment
Review Committee (MARC) Decision Document.

From:		J. Tyler

To:		Y. Donovan

Dated:		6/17/2003

MRID(s):	None

DP Barcode:	D283737

Subject:	PP’s# 2F6420.  Etoxazole.  Registration for Use on Cotton,
Pome fruits, Strawberries and Imported Oranges.  Summary of Analytical
Chemistry and Residue Data.

From:		J. Tyler

To:		S. Nguyen/D. Kenny

Dated:		7/31/2003

MRID(s):	45621724, 45621725, and 45621801 through 45621825

Attachments

Attachment 1.  Structure and Nomenclature.

Attachment 2:  IRLS Sheet.

Template Version November 2003

cc (w Attachments): J. Tyler, S. Levy

RDI: RAB1 Chemists (8/01/07); G. Kramer (8/15/07)

J.Tyler:809B:PY:(703)305-5564: 7509P:RAB1Attachment 1.  Structure and
Nomenclature.

  SEQ CHAPTER \h \r 1 Common name/(code)	Chemical name	Chemical
structure

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Attachment 2.  IRLS Sheet.

INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name:

2-(2,6-difluorophenyl)-4-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5-dihy
drooxazole	Common Name:

Etoxazole	x Proposed tolerance

( Reevaluated tolerance

( Other	Date: 3/1/07

Codex Status (Maximum Residue Limits)	U. S. Tolerances

√ No Codex proposal step 6 or above

( No Codex proposal step 6 or above for the crops requested	Petition
Number:  6E7150

DP#s: 335334

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	√No Limits

( No Limits for the crops requested	(No Limits

√No Limits for the crops requested

Residue definition:  N/A	Residue definition:  etoxazole

Crop(s)	MRL (mg/kg)	Crop(s)	MRL (mg/kg)

Notes/Special Instructions:S.funk, 03/05/2007.

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