UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

			WASHINGTON, D.C.  20460

						OFFICE OF 

						PREVENTION, PESTICIDES AND TOXIC

						 SUBSTANCES

04-Sptember-2007

MEMORANDUM

SUBJECT:	Desmedipham PC Code: 104801, Agency Test Method Review of
Proposed Tolerance Enforcement Method for Desmedipham on Spinach, Garden
Beet, Roots and Tops (PP#6E7027), Tolerance Reassessment Decision Number
364160.

				

DP Barcodes	343117,327443	MRID Numbers	46734101, 46734102

45942202, 45942201 

47212301

		 

From:		P. Yvonne Barnes 

		Reregistration Branch II/Health Effects Division (7509P)

Through:		Alan P. Nielsen, Branch Senior Scientist

		Reregistration Branch II/Health Effects Division (7509P)

To:	Richard F. Griffin, Risk Assessor

	Reregistration Branch II/Health Effects Division (7509P)

		and

	 

	Daniel Rosenblatt

	Sidney C. Jackson

	Minor Use Emergency Response Branch/Registration Division (7505P)

This document serves as an addendum to HED’s 01-February-2007 human
health risk assessment (D327443). The ACB, BEAD has reviewed the
enforcement method submitted (PP#6E7027) in support of the request for
Tolerances for the phenyl-carbamate herbicide Desmedipham. The ACB
Project # B07-22 report is attached to this summary document.

BACKGROUND

Interregional Research Project No.4 (IR-4) has submitted a petition
supporting the use of desmedipham, EPA Reg. No. 264-620, on garden beets
and spinach.  A LC/MS/MS method (AL/01/02, MRID Number 459422-02,
24-March-2003) was submitted as a tolerance enforcement method by Bayer
CropScience for desmedipham on spinach and garden beet, roots and tops
(PP#6E7027) referencing the Office of Pesticides and Toxic Substances,
OPPTS guideline 860.1340 - Residue Analytical Method.  Accordingly, the
test method was forwarded to the Analytical Chemistry Branch (ACB) for
review on 19-July-2007. The ACB has completed the review of the food
tolerance enforcement method. 

An analytical reference standard for desmedipham has been submitted to
the EPA National Pesticide Standard Repository.

recommendation

(ACB Project # B07-22, Charles J. Stafford dated 27-August-2007).

The original submitted method (AL/01/02, MRID Number 459422-02,
24-March-2003) described only one LC/MS/MS ion transition and therefore
did not meet our current requirements as a confirmatory method.  Bayer
CropScience has submitted a method addendum-1 (AL/01/02, MRID 472123-01,
10-August-2007) which provides data describing a secondary ion
transition for confirmation. The method now satisfies our OPPTS 860.1340
guideline requirements as a confirmatory method. 

COMMENTs

(ACB Project # B07-22, Charles J. Stafford dated 27-August-2007).

Analysis is by LC - MS/MS. The OPPTS 860.1340 guideline requires either
a confirmatory method or an interference study to eliminate the
possibility of false positives while using the primary enforcement
method. When mass spectrometry is used for detection in the primary
enforcement method a confirmatory method is waived as long as the
detector provides enough selectivity to eliminate false positives. While
MS/MS provides excellent selectivity, expert opinion has changed over
the past several years as mass spectrometrists have gained more
experience with the instrumentation. A single MS/MS ion transition used
to be considered sufficient for positive confirmation of analyte
residue.  However, instances of false positive interferences have led
towards consensus that two ion transitions are needed to provide
confirmation of residues. 

For this reason   SEQ CHAPTER \h \r 1 we now recommend that petitioners
provide information for two MS/MS ion transitions. When two transitions
are not available, we recommend providing an alternate chromatographic
column and/or mobile-phase combination to further reduce the possibility
of false positive residues. 

Attachment 1: Memorandum dated 27-August-2007 from Charles J. Stafford
(ACB), to P. Yvonne Barnes (HED), “Review of Proposed Tolerance
Enforcement Method for desmedipham, ACB Project # B07-22” p. 3-5. 

RDI: George J. Herndon (28-Aug-2007), Alan P. Nielsen (28-Aug-2007)

ATTACHMENT 1

  SEQ CHAPTER \h \r 1 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON D.C., 20460

Analytical Chemistry Branch

701 Maples Road

Ft. Meade, Maryland  20755-5350

  SEQ CHAPTER \h \r 1 OFFICE OF

PREVENTION, PESTICIDES AND TOXIC SUBSTANCES

         

						

August 27, 2007

MEMORANDUM

SUBJECT:	Review of Proposed Tolerance Enforcement Method for
desmedipham.  

                        ACB Project # B07-22.

	

FROM:	Charles J. Stafford, Team Leader 

		Analytical Chemistry Branch

		Biological and Economic Analysis Branch (7503P)

THRU:	Frederic L. Siegelman, Ph.D., Chief

		Analytical Chemistry Branch

		Biological and Economic Analysis Branch (7503P)

TO:		P. Yvonne Barnes, Chemist

		Registration Review Branch 2 (RRB 2)

		Health Effects Division (7509P)

			

INTRODUCTION

	The Analytical Chemistry Branch (ACB) was requested to review the food
tolerance enforcement method submitted by Bayer CropScience to support
tolerances for the herbicide desmedipham.  The ACB method review was
requested in a teleconference 7/19/07 attended by G. Herndon (HED),
Yvonne Barnes (HED) and Susan Stanton (RD).  ACB has reviewed the
proposed enforcement method data without a laboratory validation.

ANALYTICAL METHOD(S) AND DOCUMENTATION

MRID# 45942202:  Title:  “Desmedipham:  Analytical Method for the
Determination of Desmedipham (AE B038107) in Sugar Beet Tops and Roots
Using LC/MS/MS (Amended)”.  Authors:  D.J. Netzband, A.B. Wilkins. 
Completion Date:  March 24, 2003.  Sponsor:  Bayer CropScience, Research
Triangle Park, NC.  Report Number:  AL/01/02.

MRID# 45942201:  Study Title:  “Independent Laboratory Validation of
the Residue Method for Desmedipham (AE B038107) in Sugar Beet Tops Using
LC/MS/MS”.  Author:  Jeff Mollica.  Study Completion Date:  March 12,
2003.  Performing Laboratory:  Pyxant Labs Inc, Colorado Springs, CO. 
Submitting Laboratory:  Bayer CropScience, Research Triangle Park, NC. 
Report Number:  03RADPY001.  Laboratory Study ID:  Bayer-1447.

MRID# 47212301:  Report Title:  “Desmedipham:  Analytical Method for
the Determination of Desmedipham (AE B038107) in Sugar Beet Tops and
Roots Using LC/MS/MS-Addendum 1”.  Author D.J.  Netzband.  Completion
Date:  10 August, 2007.  Sponsor:  Bayer CropScience, Research Triangle
Park, NC.  Report Number:  AL/01/01-Addendum 1.

RECOMMENDATIONS

1.    SEQ CHAPTER \h \r 1 The ACB recommends that based on our review of
the proposed enforcement method, without ACB laboratory trial, Bayer
method AL/01/02 with addendum AL/01/02-Addendum 1 appears to meet the
OPPTS 860.1340 Residue Chemistry Test Guidelines for an acceptable
tolerance enforcement method.

2.  The ACB recommends that an Agency laboratory validation is not
necessary for the following reasons:

a. The method appears well-written and includes detailed instructions.

b. The method appears quick and efficient.

c. The recovery data show acceptable recoveries for all tested
commodities.

	d. The Independent Laboratory Validation (ILV) data submitted for the
method are 		acceptable and indicate that method performance is
reproducible.

3.  The original submitted method (AL/01/02) described only one LC-MS/MS
ion transition and therefore did not meet our current requirements as a
confirmatory method.  Bayer CropScience has submitted a method addendum
(AL/01/02) which provides data describing a secondary ion transition for
confirmation.  The method now satisfies our requirements as a
confirmatory method.

COMMENTS

1.  Analysis is by LC-MS/MS.  The OPP guidelines require either a
confirmatory method or an interference study to eliminate the
possibility of false positives while using the primary enforcement
method.  When mass spectrometry is used for detection in the primary
enforcement method a confirmatory method is waived as long as the
detector provides enough selectivity to eliminate false positives. 
While MS/MS provides excellent selectivity, expert opinion has changed
over the past several years as mass spectrometrists have gained more
experience with the instrumentation.  A single MS/MS ion transition used
to be considered sufficient for positive confirmation of analyte
residue.  However, instances of false positive interferences have led
towards consensus that two ion transitions are needed to provide
confirmation of residues.  References include:

Commission Decision 2002/657/EC, Official Journal of the European
Communities, August 12, 2002.

Guidance for Industry:  Mass Spectrometry for Confirmation of the
Identity of Animal Drug Residues, US FDA Center for Veterinary Medicine,
May 1, 2003.

Bethem, et al, Establishing the Fitness for Purpose of Mass
Spectrometric Methods, J Am Soc Mass Spectrom 2003, 14, 523-541.

	For this reason   SEQ CHAPTER \h \r 1 we now recommend that petitioners
provide information for two MS/MS ion transitions.  When two transitions
are not available, we recommend providing an alternate chromatographic
column and/or mobile-phase combination to further reduce the possibility
of false positive residues.

2.  An analytical reference standard for desmedipham has been submitted
to the EPA National Pesticide Standard Repository for distribution to
State and Federal regulatory labs.

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