Document ID: EPA-HQ-OPP-2007-0546-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-10-03T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

     OFFICE OF	

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date: 		July 10, 2007

MEMORANDUM

SUBJECT:	THIABENDAZOLE:  Additional Analytical Method Information to 		
Support A Threshold of Regulation Decision for the Proposed New Use as 	
a Seed Treatment for Dry Pea.  

		Petition No: PP#1E6323.  D341288

FROM:	Donna S. Davis, Chemist

		Reregistration Branch 1

		Health Effects Division (7509P)

			

THROUGH:	Michael S. Metzger, Chief

		Reregistration Branch 1

		Health Effects Division (7509P)

		Richard A. Loranger, Senior Scientist

		Christina Swartz, Chief

		Registration Action Branch 2

		Health Effects Division (7509P)

TO:		Susan Stanton

		Barbara Madden

		Risk Integration, Minor Use, Emergency Response Branch

	            Registration Division (7505P)

Attached please find additional documentation on the analytical method
used to determine field trial residues of thiabendazole in/on dry pea
when used as a seed treatment.  This information is provided to support
a Threshold of Regulation Decision for the proposed new use for
thiabendazole as a seed treatment for dry pea.

1.0	Introduction

HED previously issued a Threshold of Regulation (TOR) document to
support the requested use of thiabendazole as a seed treatment on dry
pea (D340418, 6/7/07, D. Davis).  That memorandum briefly described the
analytical method used in the dry pea field trials and concluded that
the method was sufficiently sensitive to support a threshold of
regulation decision as outlined in the Agency’s Threshold of
Regulation Policy.  This memorandum provides additional information on
the analytical method and the limit of detection of that method that
should be considered in addition to the information presented in the
June 7, 2007 document.

2.0	Analytical Method Limit of Detection

Estimated LOD

The cited analytical method had a reported lower limit of method
validation of 0.05 ppm.  The LLMV is an artifact of the concentrations
chosen for the study validation and the actual analytical limits of
quantitation and detection may be significantly below that value.  HED
carefully examined the method chromatograms.  Based on peak heights
relative to concentration, peak shape and signal to noise ratio, the
reviewer visually determined that the method limit of detection (LOD)
was no greater than 0.02 ppm.  

Supporting Radiolabelled Data

Additionally, HED reviewed data on the nature of residue in soybeans
submitted by Gustafson, Inc.  The study was entitled Total 14C
Thiabendazole Residues in Soybeans from Treated Seed Grown Under Field
Conditions.   (1998, MRID 45200301).  In this study, soybean seeds were
treated with 38 ppm 14C Thiabendazole (0.00382 lb ai/100lb seed).  The
treated seeds were then planted in the field and samples were taken of
mature dry bean (82 days after treatment).  Samples were frozen and
shipped to the laboratory for preparation and analysis. Samples were
chopped and then processed by grinding.  Samples were assayed by
combustion and analysis of 14CO2 by liquid scintillation spectrometry.  
Total radioactivity was determined in samples from the control plots and
treated plots.  Background radioactivity in the control plots were then
subtracted from the total radioactivity in the treated plots.  The TRR
in soybean seed was <0.001 ppm (<1 ppb).  

HED considers soybeans to be an appropriate surrogate for dry pea. 
Taking into account the higher application rate currently requested, the
study supports the conclusion reached in the field trial data that
residues will not exceed 0.02 ppm in dry pea grown from treated seed at
the currently requested use rate, and may be lower than 0.02 ppm.

IR-4 Statistical Analysis

Finally, IR-4 has provided statistical data on the thiabendazole
analytical method (email correspondence from D. Thompson to B. Madden
dated 7/3/07).  Those statistics are duplicated directly from that email
and support the conclusion that the actual LOD is likely below the
conservative value of 0.02 pm and indicates that the statistical LOD is
much closer to 0.01 ppm.

Calculations for LOD / LOQ for Thiabendazole/Dry Pea

Provided by IR-4

degrees of freedom	Number of Replicates	One-tailed t-statistic	 	Amount
Detected

(Spiked at

0.0480 ppm)	 

	0	1	infinity	 	0.03310

1	2	31.821	 	0.03220

2	3	6.965	 	0.03100

3	4	4.541	 	0.0385

4	5	3.747	 	0.03870

5	6	3.365	 	0.03640

6	7	3.143	 	0.04070

7	8	2.998	 

	8	9	2.896	 

	9	10	2.821	 

	10	11	2.764

11	12	2.718

12	13	2.681

13	14	2.65

14	15	2.624

15	16	2.602

16	17	2.583

17	18	2.567

18	19	2.552

19	20	2.539

20	21	2.528

21	22	2.518

22	23	2.508

23	24	2.500

24	25	2.492

25	26	2.485

Avg. Recovery	0.0358	ppm

LLMV =	0.010	ppm	Std. Dev.	One-tailed t-statistic

MDL (LOD)

For Lowest Spike Only (n = 6):	0.003727376	3.365

0.012542621

n Replicates = n-1 Deg. of Freedom	 = (t-statistic) X (Std. Dev.)

PQL (LOQ)

For Lowest Spike Only:	0.037627863

 = (MDL) X (3)

This method is based on the method described in Roy-Keith Smith's
Handbook of Environmental Analysis, Fourth Edition, Genium Publishing
Corporation.

Conclusion

The proposed use is for seed treatment to dry pea with  both field trial
data and metabolism data confirming that detectable residues are not
likely.  Further, the weight of the evidence suggests that the method
LOD is below 0.02 ppm, and may be closer to 0.01 ppm.  Finally, given
that a conservative dietary assessment assuming an LOD of 0.02 ppm
resulted in risks that were significantly below the level of concern
outlined in the TOR policy, HED concludes that the analytical method
used to generate the residue data is sufficiently sensitive to support
the threshold of regulation determination.  

3.0	Suitability of Analytical Method for Enforcement Purposes

The threshold of regulation policy stipulates that the method used to
generate residue data be suitable for enforcement purposes.  The
analytical method used to generate the cited residue data appeared in
the JAOAC, The Journal of the Association of Official Analytical
Chemists, a peer reviewed publication.  Further, adequate method
validation data were provided in both the journal article and in
conjunction with the submitted residue data.  HED concludes that the
method would be suitable for enforcement purposes.

Thiabendazole Threshold of Regulation – Analytical Method	D341288

Page   PAGE  4  of   NUMPAGES  4 

Page   PAGE  1  of   NUMPAGES  4