**UNITED STATES ENVIRONMENTAL PROTECTION AGENCY**

WASHINGTON, D.C. 20460

![](media/image1.wmf){width="0.85in" height="0.925in"}

> OFFICE OF

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date: July 10, 2007

**[MEMORANDUM]{.underline}**

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 ^14^C
Thiabendazole Residues in Soybeans from Treated Seed Grown Under Field
Conditions.* (1998, MRID 45200301). In this study, soybean seeds were
treated with 38 ppm ^14^C 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 ^14^CO~2~ 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.

+-------+--------+-------+----------+-------------+-----+------------+
| **Ca  |        |       |          |             |     |            |
| lcula |        |       |          |             |     |            |
| tions |        |       |          |             |     |            |
| for   |        |       |          |             |     |            |
| LOD / |        |       |          |             |     |            |
| LOQ   |        |       |          |             |     |            |
| for   |        |       |          |             |     |            |
| Th    |        |       |          |             |     |            |
| iaben |        |       |          |             |     |            |
| dazol |        |       |          |             |     |            |
| e/Dry |        |       |          |             |     |            |
| Pea** |        |       |          |             |     |            |
|       |        |       |          |             |     |            |
| **Pro |        |       |          |             |     |            |
| vided |        |       |          |             |     |            |
| by    |        |       |          |             |     |            |
| I     |        |       |          |             |     |            |
| R-4** |        |       |          |             |     |            |
+-------+--------+-------+----------+-------------+-----+------------+
| **de  | **     | **    |          | **Amount    |     |            |
| grees | Number | One-t |          | Detected\   |     |            |
| of    | of     | ailed |          | (Spiked at\ |     |            |
| free  | Replic | t-s   |          | 0.0480      |     |            |
| dom** | ates** | tatis |          | ppm)**      |     |            |
|       |        | tic** |          |             |     |            |
+-------+--------+-------+----------+-------------+-----+------------+
| 0     | 1      | inf   |          | 0.03310     |     |            |
|       |        | inity |          |             |     |            |
+-------+--------+-------+----------+-------------+-----+------------+
| 1     | 2      | 3     |          | 0.03220     |     |            |
|       |        | 1.821 |          |             |     |            |
+-------+--------+-------+----------+-------------+-----+------------+
| 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.  | 0.0358 | ppm   |          |             |     |            |
| Rec   |        |       |          |             |     |            |
| overy |        |       |          |             |     |            |
+-------+--------+-------+----------+-------------+-----+------------+
| LLMV  | 0.010  | ppm   | Std.     | One-tailed  |     | **MDL      |
| =     |        |       | Dev.     | t-statistic |     | (LOD)**    |
+-------+--------+-------+----------+-------------+-----+------------+
| For   |        |       | 0.0      | 3.365       |     | **0.0      |
| L     |        |       | 03727376 |             |     | 12542621** |
| owest |        |       |          |             |     |            |
| Spike |        |       |          |             |     |            |
| Only  |        |       |          |             |     |            |
| (n =  |        |       |          |             |     |            |
| 6):   |        |       |          |             |     |            |
+-------+--------+-------+----------+-------------+-----+------------+
|       |        |       |          | n           | =   |            |
|       |        |       |          | Replicates  | (   |            |
|       |        |       |          | = n-1 Deg.  | t-s |            |
|       |        |       |          | of Freedom  | tat |            |
|       |        |       |          |             | ist |            |
|       |        |       |          |             | ic) |            |
|       |        |       |          |             | X   |            |
|       |        |       |          |             | (S  |            |
|       |        |       |          |             | td. |            |
|       |        |       |          |             | De  |            |
|       |        |       |          |             | v.) |            |
+-------+--------+-------+----------+-------------+-----+------------+
|       |        |       |          |             |     |            |
+-------+--------+-------+----------+-------------+-----+------------+
|       |        |       |          |             |     | **PQL      |
|       |        |       |          |             |     | (LOQ)**    |
+-------+--------+-------+----------+-------------+-----+------------+
|       |        |       |          | For Lowest  |     | **0.0      |
|       |        |       |          | Spike Only: |     | 37627863** |
+-------+--------+-------+----------+-------------+-----+------------+
|       |        |       |          |             |     | = (MDL) X  |
|       |        |       |          |             |     | (3)        |
+-------+--------+-------+----------+-------------+-----+------------+
| This  |        |       |          |             |     |            |
| m     |        |       |          |             |     |            |
| ethod |        |       |          |             |     |            |
| is    |        |       |          |             |     |            |
| based |        |       |          |             |     |            |
| on    |        |       |          |             |     |            |
| the   |        |       |          |             |     |            |
| m     |        |       |          |             |     |            |
| ethod |        |       |          |             |     |            |
| desc  |        |       |          |             |     |            |
| ribed |        |       |          |             |     |            |
| in    |        |       |          |             |     |            |
| Roy-  |        |       |          |             |     |            |
| Keith |        |       |          |             |     |            |
| Smi   |        |       |          |             |     |            |
| th\'s |        |       |          |             |     |            |
| Han   |        |       |          |             |     |            |
| dbook |        |       |          |             |     |            |
| of    |        |       |          |             |     |            |
| Env   |        |       |          |             |     |            |
| ironm |        |       |          |             |     |            |
| ental |        |       |          |             |     |            |
| Anal  |        |       |          |             |     |            |
| ysis, |        |       |          |             |     |            |
| F     |        |       |          |             |     |            |
| ourth |        |       |          |             |     |            |
| Edi   |        |       |          |             |     |            |
| tion, |        |       |          |             |     |            |
| G     |        |       |          |             |     |            |
| enium |        |       |          |             |     |            |
| Publi |        |       |          |             |     |            |
| shing |        |       |          |             |     |            |
| Co    |        |       |          |             |     |            |
| rpora |        |       |          |             |     |            |
| tion. |        |       |          |             |     |            |
+-------+--------+-------+----------+-------------+-----+------------+

***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.