UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM

	Date:	May 08, 2007

	Subject:	Thiophanate-Methyl.  Petition for the Establishment of
Permanent Tolerances on Canola.  Estimation of MBC Method LOD and
Implications for Setting Canola Tolerance.  (PP#2E6368)  

DP Barcode:	

339582	

MRID No.: 	

45669601



PC Code:	

102001





40 CFR 180.	

371(c)	

	





	From:	Peter Savoia, Chemist

		Reregistration Branch 3

		Health Effects Division (7509P)

	Through:	William H. Donovan, Ph.D., Chemist

		Reregistration Branch 3

 		Health Effects Division (7509P)

	To:	Nathan Mottl, Chemical Review Manager 

		Reregistration Branch 1

		Special Review and Reregistration Division (7505P)

	

Background

Cerexagri, Inc. has submitted an analysis of data collected from prior
crop studies for its Topsin® M 70 WP Fungicide on canola (MRID No.
456696-01).  It contains data from three crop field trials made in 2001
for the 1x foliar application of Topsin® conducted on canola in North
Dakota (MRID No. 4554302).  It also includes results from a 2001 canola
processing study performed on Topsin® at the 0.5x, 1x, and 5x seasonal
application rates (MRID No. 45534301).  This data assessment was
undertaken to provide an estimation of the enforcement method Limit of
Detection (LOD) and Limit of Quantitation (LOQ) along with their
implications on setting the canola tolerance level.  The resulting
addendum made to these initial studies contends, using an analysis of
this data, that it is more appropriate to establish a tolerance on
canola using a lower LOQ than previously assumed.  In doing so,
Cerexagri recommends that the prescribed canola tolerance of 0.2 ppm be
reduced to 0.1 ppm using a lower LOQ as its basis.      

Topsin® M 70 WP is an EPA registered systemic fungicide manufactured
as a Wettable Powder (WP) concentrate.  Thiophanate-Methyl (TM) is the
active ingredient of Topsin®, which along with its metabolite Methyl
2-Benzimidazolyl Carbamate (MBC), is regulated by the Agency for the
purposes of tolerance enforcement.  The canola seed tolerance level
specified in 40CFR 180.371(c) is defined for residues of TM and MBC
expressed as TM.  It is calculated by multiplying the MBC result by a
factor of 1.79 to correct it for the molecular weight of the parent
compound and then adding it to the found TM concentration to derive the
total residue.  To enforce tolerances of TM and its metabolite MBC in
canola, the registrant utilizes a High Performance Liquid
Chromatography/Ultra-Violet spectroscopy (HPLC/UV) method.  The LOQ
provided by the HPLC/UV method has historically been recognized to be
0.05 ppm for most plant commodities tested.  Not withstanding many
initial problems with the adequacy of this method, it has since
undergone successful Independent Laboratory Validation (ILV) using
potatoes and peanut hay.  

The currently recommended TM tolerance for canola is 0.2 ppm and
includes regional registrations which restrict its use to Minnesota,
North Dakota, and Montana east of interstate 15. This tolerance was
derived from the enforcement method LOQ of 0.05 ppm specified for TM and
MBC analyses.  In the previous canola studies submitted to the Agency,
there were no detections of either compound at or above the LOQ level
resulting in found total TM residues of < 0.14 ppm.  This was derived by
adding the non-detected TM concentration to that of MBC expressed in TM
equivalents (0.05 ppm + [0.05 ppm x 1.79] = 0.1395 ppm).  Subsequently,
this result was appropriately rounded up to form the 0.2 ppm tolerance. 
Cerexagri believes that the use of the 0.05 ppm LOQ for MBC is not
appropriate since this is actually the Lower Limit of Method Validation
(LLMV).  They further support this claim noting that all but two samples
in the previous canola data were true non-detects for MBC.

The HPLC/UV method used by Cerexagri was specifically developed to
analyze TM and its metabolite MBC in crop commodities.  Quantitation is
made by comparing sample responses to a standard curve of known
concentrations ranging from 0.05 ppm to 1.0 ppm by linear regression. 
Using the concentration of the lowest calibration standard, the LOQ for
the method was designated to be 0.05 ppm with no LOD ever being
proposed.  In using this approach, the specified LOQ is actually the
LLMV which is simply the lowest concentration at which the method was
validated.  Estimates of practical LOD and LOQ values for analytical
methods are typically much lower than the LLMV.  The LOQ is commonly
based on the lowest concentration of a given analyte which can be
quantitated within a reasonable degree of assurance.  As such, the
Cerexagri addendum details an estimation of a practical LOD for the
metabolite MBC in canola seed using the HPLC/UV method.  Based on
further analysis of the chromatographic results from the previous canola
residue data, Cerexagri has estimated an LOD of 0.005 ppm for the
analysis of MBC.  It is generally accepted that the estimation of a
viable LOQ is usually about 3x the method LOD.  In designating an LOD of
0.005 ppm, the corresponding LOQ for MBC would be about 0.015 ppm for
the HPLC/UV method.  Therefore, specifying a 0.025 ppm LOQ, which is
half of the current LLMV, is a conservative estimate.                   

  

Cerexagri believes it is appropriate to set the tolerance level for
canola seed based on their estimated MBC LOQ rather than the LLMV. 
Thus, the 1x treated canola seed samples would result in a total TM
residue of < 0.095 ppm.  This was derived by adding the non-detected TM
concentration to that of MBC established at the new LOQ expressed in TM
equivalents (0.05 ppm + [0.025 ppm x 1.79] = 0.09475 ppm). 
Subsequently, rounding this result up to establish a 0.1 ppm canola
tolerance for the combined residue of TM and MBC would be appropriate. 
This is supported by the fact that even processing study samples treated
at the 5x rate still yield residue levels which are well below the
previously specified LOQ of 0.05 ppm.  

Conclusion

Through their analysis of the previous canola seed residue data,
Cerexagri does adequately show that its HPLC/UV method provides a 0.005
ppm LOD and a statistically valid 0.025 ppm LOQ.  It is supported by the
chromatographic results of the 5x treated samples (01ND10 TRT & 01ND11
TRT) obtained from the 2001 processing study.  The chromatograms for
these samples were the only ones to have clearly discernable MBC peaks
which can be attributed to treatment from Topsin®.  Although these
peaks are well below the 0.05 ppm level, they are sufficiently large and
their resolution distinct enough for a determination of MBC to be made. 
From the integration of these peaks, MBC residues of 0.027 ppm and 0.028
ppm were quantitated within a reasonable level of assurance.  Therefore,
based on the estimated method LOQ for MBC, HED recommends the canola
seed tolerance remain at 0.1 ppm as established by RD on 08/28/2002.  

          

 

                                   

Document Tracking

cc: J. Nevola  

RDI: W. H. Donovan (04/30/07)

Petition Number(s): PP#2E6368 

DP Barcode(s):  339582

PC Code:  102001

Template Version September 2005

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Thiophanate-Methyl	Summary of Analytical Chemistry and Residue Data
Barcode:  XXXXXX

