UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM					

DATE:                         10-JULY-2007			

SUBJECT:	Response to Deficiencies for Petition Nos. 5E7007, 5E6962,
Isoxadifen-ethyl.  Section 3 Registration on Sweet Corn, Popcorn and
Label Amendment of Field Corn.  

			

Petition No.:	5E6962, 5E7007	Chemical No.	823000

DP Numbers:	341243	Chemical Class:	Safener

40 CFR:	§180.570	MRID Numbers:	47166601





FROM:	Mohsen Sahafeyan, Chemist

Registration Action Branch 1 (RAB1)

Health Effects Division (HED) (7509P)

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

RAB1/HED (7509)

TO:			Daniel Rosenblatt/Shaja Brothers, Registration Division (RD,
7505P)

Kerry Leifer/Tracy H. Ward, RD (7505P)

Executive Summary

HED received responses from Bayer Crop Science (BCS) to deficiencies
cited in Memorandum dated 08-FEB-2007 for section 3 Registration on
sweet corn, popcorn and label amendment for field corn; these responses
are summarized below (for details see MRID 47166601):

  SEQ CHAPTER \h \r 1 Regulatory Recommendations and Residue Chemistry
Deficiencies

1)  For petition # 5E7007 (new use on sweet corn and popcorn):   

Cited in the last summary document (D324895):  Section F of the petition
should be revised to include the HED-recommended tolerances and
commodity definitions (see below).

No response as of the date of this memorandum has been received.  This
deficiency remains outstanding. 

Cited in the last summary document (D324895):  Multiresidue testing of
AE C637375 is still outstanding. 

The registrant cited a submission (MRID # 46221801) which has been
reviewed.  The study is acceptable and is forwarded to FDA.  This
deficiency is now resolved.

Provided the petitioner submits a revised section F,  HED-recommends the
following tolerances for the combined residues of the herbicide safener
isoxadifen-ethyl, [ethyl 5,5-diphenyl-2-isoxazoline-3-carboxylate], and
its metabolite AE F129431,
[4,5-dihydro-5,5-diphenyl-3-isoxazolecarboxylic acid] in/on sweet corn
and popcorn:

Corn, Sweet, (K+CWHR)	0.04 ppm

Corn, Sweet, forage	0.30 ppm

Corn, Sweet, stover	0.45 ppm

Corn, Pop, grain	0.04 ppm

Corn, Pop, stover	0.25 ppm

For petition # 5E6962 (increase use rate on field corn to 0.17 lb/A):

Cited in the last summary document (D324895):  The previously-submitted
field trial data are adequate for this petition.  New section B is
required.

The proposed labels had not stated the increase in the use rate to 0.17
lb/A.   HED received revised section B for petition # 5E6962, however,
with the same low label rates.  The registrant explained that the
petitioning for increase use rate of isoxadifen ethyl – a safener - on
field corn was to support use of tank mixtures, as well as the possible
use of more than one herbicide product within a given use season. 
Therefore, despite the provided labels did not include the increase rate
to 0.17 lb/A,HED accepted the rational.  This deficiency is now
resolved.

Cited in the last summary document (D324895):  New processing studies
are requested.  In the interim, a tolerance on corn oil should be
established based on theoretical concentration factors.

Upon rebuttal of the registrant regarding the interim tolerance, the
issue was presented to the HED Chemistry Science Advisory Council
(ChemSAC).  Chem SAC concluded that a corn processing study is to be
conducted at 5x the new field corn use rate (i.e. 5 x 0.17 lb/A). If
residues of either parent or the acid metabolite exceed the LOQ in corn
grain, then residue data in the processed fractions will be needed. 
These studies are required as conditions of registration.

		

Cited in the last summary document (D324895):  The available confined
rotational crop studies allow for soybean only with PBI of 9 months as a
rotational crop.

Upon rebuttal by  the registrant citing a previous submission that was
not reviewed (MRID # 45797401), the issue was presented to the HED
Chemistry Science Advisory Council (ChemSAC).  The preliminary review
indicated that the study included rotational crops on a plot which was
flooded with water after application of the isoxadifen ethyl to the soil
and subsequent draining of the plot after 39 days,  mimicking rice
agricultural practices.   ChemSAC accepted the study (based on low TRR
found in that study and in a corn metabolism study) toward meeting the
requirements for a rotational crop cited as a deficiency in the previous
summary document.  Provided the study is found to be acceptable after
formal review, this deficiency is resolved.

Cited in the last summary document (D324895):  Multiresidue testing of
AE C637375 is still outstanding.

The registrant cited a submission (MRID # 46221801) which had not been
reviewed.  The study is acceptable and is forwarded to FDA.  This
deficiency is now resolved.

Cited in the last summary document (D324895):  HED-recommended
tolerances:

		Corn, Field, grain
……………………………………………..0.08 ppm

		Corn, Field, forage
……………………………………………0.25 ppm

		Corrn, Field, stover
…………………………………………...0.50 ppm

The registrant also rebutted the recommended tolerances by HED based on
the exceeding number of <LOQ residue values (>60%) and inappropriateness
of using tolerance-calculator spreadsheet.  The residue values were
reexamined and it was found that although the MLE approach may not give
the best recommended tolerance value for corn field grain nevertheless,
the field corn grain should stay at the previously recommended value of
0.08 ppm for the purpose of harmonization with Canada.  For forage and
stover, because of large number of LOQ values, the traditional approach
for setting tolerance was followed; therefore, the recommended tolerance
for field corn forage (maximum residue 0.2 ppm) and stover (maximum
residue 0.4 ppm) will be 0.20 and 0.40 ppm respectively (see below).  

		

Provided the petitioner resolves the above-mentioned deficiencies and
submits a revised section F, HED recommends conditional registration and
the following tolerances for the combined residues of the herbicide
safener isoxadifen-ethyl (AE F122006), [ethyl
5,5-diphenyl-2-isoxazoline-3-carboxylate], and its metabolite AE F129431
[4,5-dihydro-5,5-diphenyl-3-isoxazolecarboxylic acid] in/on corn:

Corn, Field, grain	0.08 ppm 

Corn, Field, forage	0.20 ppm

Corn, Field, stover	0.40 ppm

RDI: RAB1 chemists (20-JUNE-2007)

Petition Number(s): 5E7007, 5E6962

DP #: 341243

PC Code: 823000

M. Sahafeyan:S10944:PY1:(703)-305-0776

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