UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                               WASHINGTON, D.C.  20460

	OFFICE OF PREVENTION, PESTICIDE
	AND TOXIC SUBSTANCES

MEMORANDUM

Date:  February 25, 2014

SUBJECT:	Thiabendazole.  PP# 3F8166.  New Seed Treatment Uses on Assorted Vegetables and Small Grains (vegetable, root (except sugar beet); subgroup1B, onion, bulb, subgroup 3-07A; Brassica, head and stem, subgroup 5A; vegetable, cucurbit group 9; alfalfa; spinach (including baby); and small grains (wheat, barley, oats, rye, and triticale).    Amendment to Increase Rate on Soybean.  Summary of Analytical Chemistry and Residue Data.  Multiresidue Method Data.

PC Code:  060101
DP Barcode:  D410807, D410833, D313507
Decision No.:  476711, 476712
Registration No.:  100-889, 100-963
Petition No.:  3F8166
Regulatory Action:  Section 3 Registration
Risk Assessment Type:  Res Chem
Case No.:  2760
TXR No.:  NA
CAS No.:  148-79-8
MRID No.:  See MRID Summary Table
40 CFR:  180.242
	Ver.Apr.08

FROM:	Susan V. Hummel, Senior Chemist
		Risk Assessment Branch 4
		Health Effects Division (7509P)

THROUGH:	Thurston G. Morton, Senior Chemist
		Risk Assessment Branch 4
		Health Effects Division (7509P)

TO:		Rosemary Kearns/Tony Kish, PM 22
		Fungicide Branch, Registration Division (7505P)

MRID Summary Table
MRID No.
Study Type
Comments
48996701
860.1500 Alfalfa
New DER; 48996701.der.doc
48996702
860.1500 Barley
New DER; 48996702.der.doc
48996703
860.1500 Wheat
860-1520 Wheat Processing
New DER; 48996703.der1.doc
New DER; 48996703.der2.doc
48996704
860.1500 Carrot, Radish
New DER: 48996704.der.doc
48996705
860.1500 Cantaloupe, Cucumber, Summer Squash
New DER; 48996705.der.doc
48996706
860.1500 Broccoli, Cabbage
New DER; 48996706.der.doc
48996707
860.1500 Spinach
New DER; 48996707.der.doc
48996708
860.1900 Field Accumulation in Rotational Crops
New DER; 48996708.der.doc
48996709
860.1500 Soybean
860.1520 Soybean processing
New DER; 48996709.der1.doc
New DER; 48996709.der2.doc
48996710
860.1500 Dry bulb onion
New DER; 48996710.der.doc
48996711
860.1340 Analytical Method in Crops
New DER; 48996711.der.doc
48996712
860.1380 Storage Stability  -  Crops
New DER: 48996712-13.der.doc
48996713
860.1380 Storage Stability  -  Processed Comodities

46469301
860.1360 Multiresidue Method
Reviewed herein

Executive Summary

Thiabendazole [2-(4-thiazolyl)benzimidazole] is a benzimidazole fungicide currently registered for use as a seed or seed piece treatment to dry pea, potato, sweet potato, soybean, and wheat.  It is also registered for use on mushrooms and is mostly used post-harvest as a dip or spray on citrus fruits, apples, pears, bananas, mangos, papaya, plantain, carrots, and potatoes.  The Thiabendazole Reregistration Eligibility Decision (RED) was issued October 2002.  A human health risk assessment was completed in June 2001 for the RED.

Tolerances for plant commodities are established under 40 CFR §180.242(a) and are expressed in terms of combined residues of thiabendazole and its metabolite benzimidazole (free and conjugated); tolerances range from 0.1 ppm for dry bean seed and soybean to 40.0 ppm for mushroom.  Tolerances for livestock commodities are established under 40 CFR §180.242(b) and are expressed in terms of combined residues of thiabendazole, 5-hydroxythiabendazole (free and conjugated), and benzimidazole.

Syngenta Crop Protection is requesting registration of new seed treatments uses on assorted vegetables and small grains (vegetable, root (except sugar beet); subgroup1B, onion, bulb, subgroup 3-07A; Brassica, head and stem, subgroup 5A; vegetable, cucurbit group 9; alfalfa; spinach (including baby); and small grains (wheat, barley, oats, rye, and triticale).  Tolerances already exist for wheat grain and wheat processed commodities.  The product to be used is Mertect 34F, a 42.3% (4.1 lb ai/gal) flowable concentrate formulation (EPA Reg. No. 100-889).  The uses are to be added to the Thiabendazole Technical label, as well (EPA Reg. No. 100-963).   The 4.1 lb ai/gal Flowable Concentrate formulation is proposed for seed treatment use at 0.0 02  -  0.1 mg ai/seed, depending on the commodity.

Syngenta is also requesting an amendment to the registration for Mertect 34F, a 42.3% (4.1 lb ai/gal) flowable concentrate formulation (EPA Reg. No. 100-889), to increase the application rate for soybean seed treatment.   This amendment is not a part of the petition; no increased tolerance is requested.

Under the current action, Syngenta has submitted a petition for tolerances associated with the proposed use, PP# 3F8166.  Tolerances at the total limit of quantitation of 0.02 ppm were proposed for residues of thiabendazole and its metabolite benzimidazole on vegetable, root (except sugar beet); subgroup1B, onion, bulb, subgroup 3-07A; Brassica, head and stem, subgroup 5A; vegetable, cucurbit group 9; alfalfa seed, forage, and hay; and spinach (including baby); and at 0.05 ppm on barley, oats, rye, and triticale grains; 0.15 ppm on barley hay and straw and rye straw; 0.2 ppm on wheat, oats, rye, and triticale forage; and 0.09 ppm on wheat hay and oats and triticale hay and straw.  Syngenta submitted residue data to support the proposed uses.  Syngenta also has included field trial and processing studies on soybean, and storage stability data, both of which were required under the Reregistration Eligibility Document (RED).  The field trial data submitted for wheat may fulfill the RED data requirement for data for wheat, and constitute a full set of residue data, so these data may be used to reevaluate the existing wheat tolerances.

The nature of the residue in plants is understood based on acceptable plant metabolism studies conducted in wheat, soybean, and sugar beet.  The residues of concern in crops for purposes of tolerance enforcement and risk assessment are thiabendazole and its metabolite benzimidazole (free and conjugated).  The nature of the residue in livestock is understood based on acceptable hen and goat metabolism studies.  The residues of concern in livestock commodities are thiabendazole, 5-hydroxy-thiabendazole (free and conjugated), and benzimidazole.  Based on the available confined rotational crop study, the residues of concern in rotated crops are the same as those in primary crops.

Acceptable enforcement analytical methods are available for thiabendazole and benzimidazole in plant commodities.  Four spectrophotofluorometric methods for the determination of thiabendazole are published in the Pesticide Analytical Manual (PAM) Vol. II, and a high performance liquid chromatography (HPLC) method with fluorescence detection (FLD) for the determination of benzimidazole (free and conjugated) is identified in the U.S. EPA Index of Residue Analytical Methods under thiabendazole as Study No. 93020.  The validated limits of detection (LODs) for the thiabendazole methods range from 0.05-0.1 ppm, and the validated limit of quantitation (LOQ) for the benzimidazole method is 0.1 ppm.

Samples from the submitted crop field trial and processing studies were analyzed for residues of thiabendazole and benzimidazole using a high performance liquid chromatography/tandem mass spectrometry (LC/MS/MS) method, GRM040.01A.  The method LOQ was 0.01 ppm, and the stated LOD was 0.004 ppm; LODs of 0.005 and 0.003 ppm were reported in the crop field trial and processing study submissions.  Adequate method validation data were submitted for the method, and the method was adequately validated concurrently with the submitted field trial and processing studies, including validation at the LOD (0.003 ppm) in the Canadian crop field trials.  HED concludes that the method is sufficiently sensitive and has been adequately validated for the purposes of making a Threshold of Regulation determination.

Adequate crop field trial data from the U.S. have been submitted to support the proposed seed treatment uses on vegetable, root (except sugar beet); subgroup1B, onion, bulb, subgroup 3-07A; Brassica, head and stem, subgroup 5A; vegetable, cucurbit group 9; alfalfa; spinach (including baby); and small grains (wheat, barley, oats, rye, and triticale).  Residues of thiabendazole and benzimidazole were each below the method LOQ of 0.01 ppm (total LOQ of 0.02 ppm) in all samples of vegetable, root (except sugar beet); subgroup1B, onion, bulb, subgroup 3-07A; Brassica, head and stem, subgroup 5A; vegetable, cucurbit group 9; alfalfa; and spinach.  Finite residues were reported in some samples of barley and wheat grain, forage, hay and straw.  Additionally, field trial data were submitted for soybeans, in response to a RED data requirement.  The wheat and soybean field trial data submitted with this petition satisfy the RED data requirement for additional field trial data for wheat and soybeans.

Adequate wheat and soybean processing studies were submitted, both reflecting a 5x application rate.  The soybean processing study was submitted in response to a RED data requirement.  The wheat samples treated at a 5x application rate were processed into bran, flour, middlings, shorts and germ using simulated commercial procedures.  Residues of thiabendazole were nonquantifiable in wheat grain and all wheat processed commodities.  The soybean samples treated at a 5x application rate were processed into meal, hulls, refined oil, flour, milk, tofu, soy sauce, miso, pollard and crude oil using simulated commercial procedures.  Residues of thiabendazole were nonquantifiable in soybeans and all soybean processed commodities.   Therefore, HED concludes that residues of thiabendazole or its regulated metabolite, benzimidazole, are not likely to concentrate in the processed commodities of wheat and soybeans.

A limited field rotational crop study was required in the RED and was included in the current submission.  In 13 rotational crop trials, after application to the soil at a rate typical of seed treatment application rates, residues of thiabendazole and benzimidazole were nonquantifiable (<0.02 ppm total) in samples of lettuce, radish, and wheat commodities planted 30, 60, and 270 days after treatment.  This study satisfies the RED data requirement for rotational crop studies.

Regulatory Recommendations and Residue Chemistry Deficiencies

Based on residue chemistry considerations only,   HED concludes that tolerances can be supported for residues of thiabendazole and its regulated metabolite benzimidazole in vegetable, root (except sugar beet); subgroup1B, onion, bulb, subgroup 3-07A; Brassica, head and stem, subgroup 5A; vegetable, cucurbit group 9; alfalfa; spinach (including baby); or small grain (wheat, barley, oats, rye, and triticale) commodities grown from treated seed; in the processed commodities of wheat; and in rotational crops as a result of seed treatment use proposed in this petition.  The recommended tolerances may be found in Table 7 of this document.

The current tolerance expression is not in accord with our current guidance.  See recommendation in Section 860.1550 Proposed Tolerances.  Updating the tolerance expression will be accomplished during registration review.

International Harmonization.  Neither CODEX, nor Canada have established MRLs for thiabendazole on the proposed commodities.  There is no issue with International Harmonization for the current petition.

Provided that the use directions are revised as requested, analytical standards are submitted as requested, and the storage stability studies reported here as an interim report, are completed and submitted as final reports, HED concludes that, based on the available residue data, the requested use of thiabendazole as a seed treatment for vegetable, root (except sugar beet); subgroup1B, onion, bulb, subgroup 3-07A; Brassica, head and stem, subgroup 5A; vegetable, cucurbit group 9; alfalfa; spinach (including baby); and small grains (wheat, barley, oats, rye, and triticale) may be registered once tolerances are established as recommended in Section 860.1550 Proposed Tolerances.

A human health risk assessment for thiabendazole will be conducted in connection with this action.

860.1200 Directions for Use

   * The registrant should revise the label to include the use rates in terms of weight of product per weight of seed (e.g. g/100 kg seed).

860.1380 Storage Stability

   * The storage stability studies currently in progress (reported in an interim report) must be completed to fully support the field trial and processing studies for the current petition.
   *

860.1650 Submittal of Analytical Reference Standards

   * For benzimidazole, a new standard must be submitted.  For 5-hydroxy-thiabendazole, the registrant must either recertify the lot in the repository and send in an updated certificate of analysis (COA), or submit new standards (different lot #) if the previous lots will not be recertified.

Background

The chemical structure and nomenclature of thiabendazole and its regulated metabolites are presented in Table 1, and the physicochemical properties of the technical grade of thiabendazole are presented in Table 2.

Table 1.	Test Compound Nomenclature.
Compound

Common name
Thiabendazole
Company experimental name
None
IUPAC name
2-(thiazol-4-yl)benzimidazole
CAS name
2-(4-thiazolyl)-1H-benzimidazole
CAS registry number
148-79-8
End-use product (EP)
4.1 lb ai/gal FlC formulation (Mertect 34F; EPA Reg. No 100-889)
Compound

Common name
Benzimidazole
Chemical name
1H-benzimidazole
CAS registry number
51-17-2
Compound

Common name
5-hydroxy-thiabendazole
Chemical name
2-(1,3-thiazol-4-yl)-1H-benzimidazol-5-ol)

Table 2.	Physicochemical Properties of the Technical Grade Test Compound: Thiabendazole.
Parameter
Value
Reference
Melting point/range
304-305 °C
Thiabendazole RED 10/02
pH
5.16-5.97
Thiabendazole RED 10/02
Density
25-30 cc (tapped)
Thiabendazole RED 10/02
Water solubility
0.028-0.030 mg/mL at 25 °C
Thiabendazole RED 10/02
Solvent solubility

acetone
benzene
chloroform
dimethylformamide
dimethyl sulfoxide
ethanol
ethyl acetate
methanol
25 ºC
4.2 g/L
230 mg/L
80 mg/L
39 g/L
80 g/L
7.9 g/L
2.1 g/L (R.T.)
9.3 g/L
The Pesticide Manual, 8[th] edition
Vapor pressure
4 x 10 [-9] mm Hg at 25 °C
Thiabendazole RED 10/02
Dissociation constant, pKa
Pka1 = 4.73; Pka2 = 12.00
Thiabendazole RED 10/02
Octanol/water partition coefficient
Log(KOW) = 240-285 at pH 7
Thiabendazole RED 10/02
UV/visible absorption spectrum
Neutral solution
32,170 L/mol*cm[3] at 205.5 nm
Acidic solution
41,520 L/mol*cm[3] at 303.5 nm
Neutral solution
40,553 L/mol*cm[3] at 215.5 nm
MRID 46286801[1]
[1] Data were referenced in MRID 47705121.

860.1200 Directions for Use

Syngenta has submitted a draft label (dated 10/23/2013) and a description of the proposed use for the 4.1 lb ai/gal FlC formulation (Mertect 34F Fungicide; EPA Reg No. 100-889).

The proposed use directions for corn are summarized in Table 3.

Table 3.	Summary of Directions for Use of Thiabendazole.
Applic. Timing, Type, and Equip.
                                  Formulation
                                [EPA Reg. No.]
                                 Applic. Rate
                          Max. No. Applic. per Season
                                      PHI
                                    (days)
                        Use Directions and Limitations
                                    Alfalfa
Seed treatment,
Seed treatment application equipment
                                4.1 lb ai/gal F
                                   [100-889]
                   0.004 mg ai/seed or 5.8 fl oz/100 lb seed
                                       1
                                      N/A
Assumes an average seed size of
210,000 seeds/lb
             Cereal Grains  -  Barley, Oats, Rye, Triticale, Wheat
Seed treatment,
Seed treatment application equipment
                                4.1 lb ai/gal F
                                   [100-889]
                               0.03 mg ai/seed
                         Barley 2.6 fl oz/100 lb seed
                          Oats 3.4 fl oz/100 lb seed
                           Rye 3.2 fl oz/100 lb seed
                        Triticale 2.6 fl oz/100 lb seed
                          Wheat 3.1 fl oz/100 lb seed

                                       1
                                      N/A

Barley- assumes an average seed size of 12,500 seeds/lb
Oats- assumes an average seed size of 12,500 seeds/lb
Rye - assumes an average seed size of 15,600 seeds/lb
Triticale - assumes an average seed size of 12,750 seeds/lb
Wheat - assumes an average seed size of 15,000 seeds/lb
Brassica Head & Stem subgroup; Bulb Vegetables; Vegetables, Root subgroup (except sugar beets)
Seed treatment,
Seed treatment application equipment
                                4.1 lb ai/gal F
                                   [100-889]
                               0.002 mg ai/seed
                                       1
                                      N/A

                              Cucurbit Vegetables
Seed treatment,
Seed treatment application equipment
                                4.1 lb ai/gal F
                                   [100-889]
                                0.1 mg ai/seed
                                       1
                                      N/A

                                    Spinach
Seed treatment,
Seed treatment application equipment
                                4.1 lb ai/gal F
                                   [100-889]
                               0.006 mg ai/seed
                                       1
                                      N/A

                                   Soybeans
Seed treatment,
Seed treatment application equipment
                                4.1 lb ai/gal F
                                   [100-889]
                                0.03 mg ai/seed
                                       1
                                      N/A

No specific tank mix partners are identified; the label states, "This product must not be tank mixed with any pesticide unless physical compatibility and phytotoxicity tests have been completed and proved to be satisfactory."

The label also notes that Federal law requires that bags containing treated seed shall be labeled with the following information:  "This seed has been treated with thiabendazole fungicide.  Do not use for feed, food, or oil purposes.  Store away from feeds and foodstuffs.  Do not allow children, pets or livestock to have access to treated seeds."  The label also states, " Wear long pants, long-sleeved shirt and protective gloves when handling treated seed.  Use an EPA-approved dye or colorant that imparts an unnatural color to the seed as required in 40 CFR 153.155 (c).  Do not feed vines or hay grown from treated seed to livestock.  Do not plant any crop, other than soybeans, dry peas, barley, wheat, oats, rye, and triticale, brassica head and stem subgroup 5A, cucurbit vegetable crop group 9, root vegetables (except sugar beets) subgroup 1B, bulb vegetables subgroup 3-07A, spinach and alfalfa, within 30 days to fields in which treated seeds were planted."

Conclusions.  The proposed use directions are adequate to allow evaluation of the residue data presented herein.  The submitted corn field trials were conducted according to the proposed use pattern, and the pre-grazing interval specified for corn forage is supported by the available data.  Rates must also be stated in terms of lb ai (or product)/A.

860.1300 Nature of the Residue - Plants
47705109.der.doc
Revised Residue Chemistry Chapter of the Thiabendazole RED DP# 267871, 9/7/00, T. Morton

The qualitative nature of the residue in plants is adequately understood based on soybean, sugar beet, and wheat metabolism studies.  The residues of concern in plants include thiabendazole and benzimidazole, free and conjugated.

In support of the registered seed treatment use on corn, Syngenta Crop Protection submitted a study investigating the metabolism of [phenyl-U-[14]C]thiabendazole  in seed-treated corn.  The test substance, formulated as a suspension concentrate (SC) formulation, was applied as a seed dressing to corn seed at 1.8x the proposed seed treatment rate for corn.  Immature corn forage was collected at the final vegetative stage (V12), 81 days after planting (DAP); sweet corn cobs, kernels, and foliage (forage) were collected at the dough stage (R4), 101 DAP; and mature corn cobs, kernels, and foliage (stover) were collected at the R6 stage, 116 DAP.

TRR were 0.014 ppm in immature corn forage harvested at the V12 stage; 0.005 ppm in sweet corn forage harvested at the dough stage; and 0.002 ppm in mature corn stover harvested at the R6 stage.  TRR were nondetectable in sweet corn kernels and cobs and mature corn kernels and cobs.

Only immature corn forage was extracted; all other corn matrices had TRR <0.01 ppm.  Approximately 43% of the radioactivity was extracted from immature forage with ACN/water.  The extract was separated into organic (13% TRR) and aqueous (16% TRR) phases; a 32% loss occurred with concentration for phase separation.  Nonextractable residues accounted for ~56% TRR (0.008 ppm).  Accountability was 98%.

Although the extractable radioactivity was low (0.006 ppm) in immature forage, the organic and aqueous phases were analyzed using normal and reverse phase TLC.  Using normal phase TLC, radioactivity in the aqueous fraction was immobile; radioactivity in the organic phase moved from the origin, but distinct components were not resolved.  With reverse phase TLC, radioactivity in both the aqueous and organic phases was diffused up the plate.  Radioactivity was observed at the origin, near the origin, and up most of the plate, indicative of varying polarity.  Using normal and reverse phase TLC, no distinct component could be resolved which corresponded to thiabendazole.

The study results demonstrate that metabolism of thiabendazole in corn at early growth stages (immature forge) results in multiple minor components of greater polarity than the parent.  With plant growth, the TRR in foliage decreases, either by release as CO2 or dilution with increasing biomass.  There was no evidence of translocation of residues into the reproductive parts of the plant including kernels and cobs.

860.1300 Nature of the Residue - Livestock
Revised Residue Chemistry Chapter of the Thiabendazole RED DP# 267871, 9/7/00, T. Morton

The qualitative nature of the residues in livestock is adequately understood based upon acceptable ruminant and poultry metabolism studies.  The residues of concern in livestock commodities include thiabendazole, 5-hydroxy-thiabendazole (free and conjugated), and benzimidazole.

860.1340 Residue Analytical Methods
48996711	860.1340 Analytical Method in Crops
Revised Residue Chemistry Chapter of the Thiabendazole RED DP# 267871, 9/7/00, T. Morton
Residue Chemistry Memo DP#s 207850, etc., 1/8/99, S. Mason

Plant commodities

Enforcement analytical method:  Adequate analytical methodology is available for data collection and enforcing tolerances of residues of thiabendazole per se.  PAM Vol. II lists four spectrophotofluorometric methods (Methods I, A, B, and C) for determining residues of thiabendazole per se in or on plant commodities.  In all of the methods, residues are extracted with ethyl acetate, and the extracts are purified by washing with dilute NaOH and/or HCl.  The LODs range from 0.05-0.1 ppm.

In addition, an HPLC method with fluorescence detection (FLD) is available for the enforcement of tolerances for residues of free and conjugated benzimidazole.  This method is listed in the U.S. EPA Index of Residue Analytical Methods under thiabendazole as Study No. 93020 (MRID 43328302).  The metabolite benzimidazole (and benzimidazole-related compounds) are extracted from plant commodities with methanol and refluxing with 3 N KOH-rnethanol. The KOH is precipitated with concentrated hydrochloric acid.   The enzyme β-glucosidase is used to free benzimidazole from benzimidazole-related compounds.  The residues are acidified with HCI and the aqueous portion is separated and cleaned up with ethyl acetate, pH adjusted to 9-12, extracted  with ethyl acetate.  The residue is reconstituted with 1% ammonium acetate in water and analyzed for benzimidazole by reverse phase HPLC using a Supelco LC-8-DB, column (or equivalent) with a mobile phase of 750 mL water:250 mL methanol:1 g ammonium acetate and  fluorescence detection.   The reported LOQ is 0.1 ppm, and the LOD is 0.05 ppm in wheat grain, straw, and processed wheat commodities.

Data collection methods:  Syngenta Crop Protection, Inc. has submitted an LC/MS/MS method, GRM040.01A, for the determination of residues of thiabendazole and benzimidazole in crop matrices.  The method was used for data collection in the submitted U.S. and Canadian corn field trials and the corn processing study.

Syngenta noted that the extraction procedures for Method GRM040.01A were adapted from Merck Methods M-041 and M-056 (reviewed under DP#s 207850, etc.) but that clean-up steps were removed, and MS/MS detection was used instead of FLD.

Briefly, homogenized crop samples are extracted with 0.025 M KH2PO4 (pH 6):ethyl acetate (25:10, v:v) and centrifuged.  The ethyl acetate phase is collected, and the resulting aqueous phase is partitioned twice more with ethyl acetate followed by centrifugation.  The ethyl acetate phases are combined with the original ethyl acetate phase, and the aqueous phase is subjected to evaporation at 40 °C to remove ethyl acetate, and acidified to pH 5.3-5.5 with concentrated H3PO4.  The acidified extract is subjected to enzyme hydrolysis with β-glucosidase (for 2 hours at 38 °C) to remove conjugates, after which the hydrolysate is adjusted to pH 6.0-6.2 with 1 M NaOH and partitioned with ethyl acetate (three times).  The resulting ethyl acetate phases are combined with the ethyl acetate phases that were previously collected, adjusted to volume as necessary with ethyl acetate, and redissolved in methanol for LC/MS/MS analysis.  The method monitors a single ion transition for each analyte.  The method LOQ is 0.01 ppm, and the LOD is 0.004 ppm.  The registrant adequately explained how the LOQ and LOD were determined.

The method was adequately validated using samples of field corn forage, grain, and stover, and sweet corn forage and K+CWHR fortified with each analyte at 0.01, 0.05, and 0.1 ppm.   Overall recoveries were 81-118% (average of 104% and standard deviation of 7.4%) for thiabendazole and 71-119% (average of 95% and standard deviation of 12%) for benzimidazole.

Acceptable concurrent recovery data for the method were also submitted with the submitted U.S. and Canadian field trials and the field corn processing study.  Concurrent recoveries were generally in the acceptable range of 70-120% for all raw agricultural and processed corn commodities.  We note that fortification levels in the concurrent method validation conducted with analysis in the Canadian field trials included the stated LOD of 0.003 ppm.

No confirmatory procedures, independent laboratory validation (ILV), or radiovalidation data were included in the method submission.  Because the method is not intended as an enforcement method, confirmatory procedures and ILV are not required.  No radiovalidation data are required for the method because the extraction procedures are similar to those used in the plant metabolism studies for thiabendazole (refer to DP# 165718, 3/11/92, L. Cheng).

Samples from the banana and citrus storage stability study submitted under DP# 363974 were analyzed for residues of benzimidazole using Merck Methods M-057 and M-058, respectively.  The HPLC/FLD methods are essentially identical, except that they are written for the specific crop.  The reported method LOQ was 0.07 ppm for benzimidazole.

Briefly, homogenized samples were mixed with pH 8.0 buffer (adjusted as necessary with 0.2 N NaOH for citrus samples), extracted with ethyl acetate (2-3x), and centrifuged.  The ethyl acetate extracts were applied to a cation exchange solid phase extraction column, and residues of benzimidazole were eluted with acetonitrile (ACN):water (30:70, v:v) containing 0.1 M KH2PO4.  The eluate was adjusted to volume with ACN/water for analysis by cation exchange HPLC/FLD.

The methods were adequate for data collection based on acceptable concurrent method recoveries; recoveries were within the acceptable range of 70-120% for banana and orange samples fortified with benzimidazole at 0.10 ppm.

Conclusions.  The residue analytical methods data are adequate for data collection and enforcement.

860.1360 Multiresidue Methods
Revised Residue Chemistry Chapter of the Thiabendazole RED DP# 267871, 9/7/00, T. Morton
MRID 46469301

The FDA PESTDATA database (June 2005) indicates that thiabendazole is completely recovered using FDA Multiresidue methods 302 and 404, and is not recovered through method 303.  Thiabendazole was not tested through method 304.  Data on the recovery of the metabolites 5-hydroxy-thiabendazole and benzimidazole through FDA Multiresidue Protocols were submitted in response to the Thiabendazole RED (MRID 46469301).

5-Hydroxy-thiabendazole was found to be amenable to GC, but was not recovered through Section 302 Multiresidue Method. 5-Hydroxy-thiabendazole was also tested through Protocol A because it is a naturally fluorescent compound, but it did not chromatograph well on the LC system. Testing for 5-hydroxy-thiabendazole was terminated according to the Pesticide Analytical Manual, Vol. I (PAM 1)1, Decision Tree. No Multiresidue Method will be suitable for analysis of 5-Hydroxy-thiabendazole.

Benzimidazole (CGA-18306) was amenable to GC, but was not recovered through Section 302 Multiresidue Method. Benzimidazole was also tested through Protocol A because it is a naturally fluorescent compound, but did not produce adequate responses on the LC system. Testing for benzimidazole was terminated according to PAM I Decision Tree. No Multiresidue Method will be suitable for analysis of CGA-l 8306.

Conclusions.  The data required in the Thiabendazole RED reflecting recovery of residues of benzimidazole through the FDA multiresidue methods have been provided.

Thiabendazole is completely recovered using FDA Multiresidue methods 302 and 404, and is not recovered through method 303.  Benzimidazole and 5-hydroxy-thiabendazole are not recovered by the FDA multiresidue methods.

860.1380 Storage Stability
48996712	860.1380 Storage Stability  -  Crops
48996713	860.1380 Storage Stability  -  Processed Comodities
Residue Chemistry Memo DP# 270154, 2/22/01, T. Morton
Revised Residue Chemistry Chapter of the Thiabendazole RED DP# 267871, 9/7/00, T. Morton
Residue Chemistry Memo DP# 196149, 4/14/94, F. Suhre
Residue Chemistry Memo DP# 186592, 7/30/93, J. Abbotts

Storage stability data reviewed prior to the Thiabendazole RED (summarized in DP# 267871) indicated that residues of thiabendazole and benzimidazole are stable for up to 28 months in mushrooms stored at -23 °C; for up to 27 months in whole potatoes and wet peel stored at <=0 °C; for up to 23 months in wheat grain and straw at <=-15 °C; and for up to 18 months in wheat bran and flour stored at <=-15 °C.  In addition, storage stability data were reviewed prior to the RED indicating that residues of thiabendazole are stable for up to 9 months in apples, apple juice, and dried pomace store at -15 °C; for up to 3 months in whole bananas and banana pulp stored at -20 °C; and for up to 9 months in citrus fruit, oil, molasses, and pulp stored at -26 °C.

Additional storage stability data for soybean are available (D267871) indicating that residues of thiabendazole are stable in soybean forage hay and seed stored at ~-20 °C for up to 1 year.   Data  demonstrate that residues of benzimidazole are relatively stable in banana stored frozen for up to 3 months and in orange stored frozen for up to 6 months.

In the current submission, Syngenta Crop Protection, LLC has submitted the results of storage stability studies with thiabendazole and metabolite benzimidazole in representative raw agricultural commodities (RACs; MRID 48996712), including dry navy bean, soybean seed (oil seed), spinach leaves (leafy vegetable), barley grain (non-oily grain), and orange (whole fruit; acidic fruit), and processed commodities (MRID 48996713) soybean oil and tomato puree.    Samples in the study were stored at -20C.  The RAC study is an interim report reflecting storage intervals of ~0, 3, and 9 months; the submission indicates that the study will be conducted through 24 months.   The processed commodity study reflects storage intervals of ~0, 3, 6, 9 and 12 months.  For both studies, samples of untreated commodities were fortified with thiabendazole or benzimidazole at 0.1 ppm for each analyte and stored at ~-20 °C.  Both studies were conducted by Morse Laboratories (Sacramento, CA).

The study indicates that residues of thiabendazole and metabolite benzimidazole are stable in dry navy bean, soybean seed, spinach leaves, barley grain and orange stored frozen (-20 +- 5 °C) for up to 8.9-9.9 months (271-300 days; the length of the study), and that residues of these analytes are stable in soybean oil and tomato puree stored frozen (-20 to -10 °C) for up to 12.0-12.1 months (365-367 days; the length of the study).    Storage stability of benzimidazole in spinach was low at the 9 month sampling interval.

The storage durations and conditions of samples from the submitted seed treatment field trials and processing study are presented in Table 4.

Table 4.	Summary of Storage Conditions and Durations of Samples from the Corn Crop Field Trial and Processing Studies.
Matrix
                              Storage Temperature
                                     (°C)
                            Actual Storage Duration
                  Interval of Demonstrated Storage Stability
Alfalfa forage
                                    <=-10
                         40-366 days (1.3-12.0 months)
Thiabendazole is reasonably stable under frozen storage conditions in/on wheat grain and straw for up to 23 months and in/on soybean forage, hay, and seed for up to 1 year.
Acceptable storage stability data have been submitted demonstrating that residues of thiabendazole and benzimidazole in/on representative raw agricultural commodities are stable during frozen storage for up to ~10 months.
Alfalfa hay

                         40-426 days (1.3-14.0 months)

Alfalfa seed

                          40-89 days (1.3-2.9 months)

Barley Grain
                             -10 at prep facility
                         -25 at analytical laboratory
                         87-388 days (2.9-12.8 months)

Barley Hay

                         69-354 days (2.3-11.6 months)

Barley Straw

                         90-392 days (3.0-12.9 months)

Wheat Grain

                         59-359 days (1.9-11.8 months)

Wheat Forage

                         61-353 days (2.0-11.6 months)

Wheat Hay

                         81-361 days (2.7-11.9 months)

Wheat Straw

                         58-323 days (1.9-10.6 months)

Carrot
                             -10 at prep facility
                      -25 - -20  at analytical laboratory
                         90-257 days (3.0-8.5 months)
Acceptable storage stability data have been submitted demonstrating that residues of thiabendazole and benzimidazole in/on representative raw agricultural commodities are stable during frozen storage for up ~10 months.
Radish

                         157-290 days (5.2-9.5 months)

Cantaloupe

                         51-396 days (1.7-13.0 months)

Cucumber

                        176-311 days (5.8-10.3 months)

Summer Squash

                        197-330 days (6.5-10.9 months)

Broccoli
                             -10 at prep facility
                         -20 at analytical laboratory
                         93-308 days (3.1-10.1 months)
Acceptable storage stability data have been submitted demonstrating that residues of thiabendazole and benzimidazole in/on representative raw agricultural commodities are stable during frozen storage for up to ~10 months.  Residues of benzimidazole may decline slightly in/on spinach during frozen storage (corrected recovery of ~66% at 9 months).
Cabbage

                         124-300 days (4.1-9.9 months)

Spinach

                         43-248 days (1.4-8.2 months)

Dry Bulb Onion

                         73-140 days (2.4-4.6 months)

Rotational Lettuce
                                      -10
                         70-167 days (2.3-5.5 months)

Rotational Radish

                         30-211 days (1.0-6.9 months)

Rotational Wheat

                         71-348 days (2.3-11.4 months)

Soybean forage
              -10 at prep facility; -20 at analytical laboratory
                         221-273 days (7.3-9.0 months)
Acceptable storage stability data have been submitted demonstrating that residues of thiabendazole and benzimidazole in/on representative raw agricultural commodities are stable during frozen storage for up to ~10 months
Soybean hay

                         22-274 days (7.3-9.0 months)

Soybean seed

                        181-224 days (6.0-7.4 months)

Processing study (samples analyzed for thiabendazole only)
Wheat Grain
                                    <=-10
                        129-414 days (4.2-13.6 months)

Thiabendazole is relatively stable in various crops, including wheat grain for up to 23 months of frozen storage and 22 months in/on soybean grain.
Soybean Grain

                         109-125 days (3.6-4.1 months)

Wheat Bran

                          75-96 days (2.5-3.2 months)
Thiabendazole is relatively stable in various processed commodities, including citrus oil for 9 months, and wheat bran and flour for up to 18 months of frozen storage, and 12 months in soybean oil
Wheat Flour

                          47-68 days (1.5-2.2 months)

Wheat Middlings

                          39-60 days (1.3-2.0 months)

Wheat Shorts

                          46-67 days (1.5-2.2 months)

Wheat Germ

                          43-63 days (1.4-2.1 months)

Soybean Processed commodities

                         33-94 days (1.1 - 3.1 months)

Conclusions.  The available and submitted storage stability data are not adequate to support the storage durations and conditions of samples from the corn crop field trial and processing studies.  The storage stability studies currently in progress (reported in an interim report)  must be completed to adequately support the field trial and processing studies for the current petition.

860.1400 Water, Fish, and Irrigated Crops

The proposed use is not relevant to this guideline topic.

860.1460 Food Handling

This topic is not relevant to the proposed use.

860.1480 Meat, Milk, Poultry, and Eggs

Although there are livestock feed stuffs associated with the proposed use on corn, because residues were nonquantifiable in all field trial samples, the dietary burdens to livestock will not be affected.  Therefore, data requirements pertaining to meat, milk, poultry, and eggs are not relevant to this action.

860.1500 Crop Field Trials
48996701	860.1500 Alfalfa
48996702	860.1500 Barley
48996703	860.1500 Wheat
48996704	860.1500 Carrot, Radish
48996705	860.1500 Cantaloupe, Cucumber, Summer Squash
48996706	860.1500 Broccoli, Cabbage
48996707	860.1500 Spinach
48996708	860.1900 Field Accumulation in Rotational Crops
48996709	860.1500 Soybean
48996710	860.1500 Dry bulb onion

Alfalfa.  Twelve alfalfa forage and hay field trials were conducted in the United States during the 2011-2012 growing seasons in the North American Free Trade Agreement (NAFTA) Growing Zones 1 (PA; 1 trial); 2 (GA; 1 trial), 5 (MN, IA, ND, NE, WI; 6 trials), 7 (NE; 1 trial), 9 (UT; 1 trial), 10 (CA; 1 trial), and 11 (ID; 1 trial).  Two additional trials were conducted for collection of alfalfa seed only in NAFTA Growing Zones 9 (ID; 1 trial) and 10 (CA; 1 trial).

A flowable concentrate (water-dispersible suspension) for seed treatment (FS) formulation (Mertect(R) 340-F) containing 4.1 lb ai/gal thiabendazole was applied to alfalfa seeds before planting.  The seeds were treated at the Syngenta Seeds facility (Stanton, MN) using commercial seed treatment procedures.  The test substance was applied to the seeds using a CC20 or R12 seed treater.  Application rates for thiabendazole were 0.003-0.05 lb ai/A (3.4-56 g ai/ha).  Application rates in lb ai/A were calculated by the petitioner from approximate seeding rate (387,659 seed/A to 5,140,777 seed/A) and actual application rate (0.003-0.004 mg ai/seed).  The nominal application rate was 0.004 mg ai/seed.  Composite seed samples from two trials were shipped to SGS NAM GLP Laboratory (Brookings, SD) to confirm treatment rates.  Actual treatment rates were 85-100% of the target rate.  For each trial site, samples of treated seeds were planted within 8-138 days of treatment (forage and hay field trials) and 207-347 days of treatment (seed field trials).  First, second, and third cuttings of alfalfa forage and hay were harvested from twelve trials at 45-253, 70-292, and 110-323 days after planting (DAP), respectively.  Hay samples were not dried prior to collection.  Seed samples were collected from two trials 185-374 DAP.

Samples were analyzed for residues of thiabendazole and benzimidazole using a liquid chromatography method with tandem mass spectrometry detection (LC/MS/MS), Method GRM040.01A.  This method was previously reviewed by the Agency and was found to be acceptable for data collection (refer to 47705110.DER1, DP# 363974, 11/30/09, S. Hummel).  The limit of quantitation (LOQ; determined as the lowest level of method validation, LLMV) was 0.01 ppm for each analyte in each alfalfa matrix, for a combined LOQ of 0.02 ppm.  The method was adequate for data collection based on acceptable concurrent recovery data.  The fortification levels used in concurrent method recovery were adequate to bracket expected residue levels.  Concurrent recoveries were corrected for apparent residues in controls; residues in the treated samples were not corrected for apparent residues in controls.  The method does not provide for conversion of residues of benzimidazole to parent equivalents.

Samples of alfalfa were stored frozen (frozen at the field sites, <-10 °C at the preparation facility, -25 to -10 °C at the analytical laboratory) from collection to analysis for 40-366 days (1.3-12.0 months) for forage, 40-426 days (1.3-14.0 months) for hay, and 40-89 days (1.3-2.9 months) for seed.  Samples were analyzed within 1-12 days of extraction.  Acceptable storage stability data have been submitted demonstrating that residues of thiabendazole and benzimidazole in/on representative raw agricultural commodities are stable during frozen storage for up to ~10 months (refer to 48996712.der, interim report).  In addition, storage stability data are available indicating that residues of both analytes are stable during frozen storage for up to 23 months in/on wheat grain and straw (refer to the Residue Chemistry Chapter of the Thiabendazole RED; DP# 267871, 9/7/00, T. Morton) and for up to 22 months in/on soybean forage, hay, and seed (DP# 280701, 12/9/10, T. Morton).  These data are adequate to support the sample storage conditions and durations for the submitted study.

In crops grown from seed treated with the 4.1 lb ai/gal FS formulation of thiabendazole at 0.02-0.05 lb ai/A (22-56 g ai/ha), residues of thiabendazole and benzimidazole were each below the LOQ (<0.01 ppm) in/on all samples of alfalfa forage and hay harvested 45-253 (first cutting), 70-292 (second cutting), and 110-323 DAP (third cutting); combined residues were <0.02 ppm in/on all samples.  In crops grown from seed treated with the 4.1 lb ai/gal FS formulation of thiabendazole at 0.003-0.04 lb ai/A (3.4-45 g ai/ha), residues of thiabendazole and benzimidazole were each below the LOQ (<0.01 ppm) in/on all samples of alfalfa seed harvested 185-374 DAP; combined residues were <0.02 ppm in/on all samples.

Residue decline data were not submitted; however none are required because the pesticide is applied before the edible portion of the crop has formed.

Barley.  Twelve field trials were conducted in the United States during the 2011 growing season in the North American Free Trade Agreement (NAFTA) Growing Zones 2 (VA; 1 trial), 5 (MN, IA, ND; 3 trials), 7 (ND and NE; 4 trials), 9 (CO; 1 trial), 10 (CA; 1 trial), and 11 (ID and OR; 2 trials).

A flowable concentrate (water-dispersible suspension) for seed treatment (FS) formulation (Mertect(R) 340-F) containing 4.1 lb ai/gal thiabendazole was applied to barley seed before planting.  The seed was treated at the SGS North America, Inc. facility (Brookings, SD) using commercial seed treatment procedures.  The test substance was applied to the seed using a Hege Treater.  Application rates for thiabendazole were 0.03-0.20 lb ai/A (34-224 g ai/ha).  Application rates in lb ai/A were calculated by the petitioner from approximate seeding rates (550,349-3,085,519 seed/A) and actual seed treatment rates (0.028-0.030 mg ai/seed).  The nominal seed treatment rate was 0.03 mg ai/seed.  Composite seed samples were shipped to SGS NAM GLP Laboratory (Brookings, SD) to confirm treatment rates.  Actual seed treatment rates were 92.1-101% of the target rate.  The petitioner noted that the application rate at the CA site (0.20 lb ai/A) was high due to the use of a higher than normal seeding rate.   For each trial site, treated seed was planted within 6-69 days of treatment.  Samples of barley hay and grain and straw, respectively, were harvested from all trials 52-242 and 83-256 days after planting (DAP).  Hay samples were not dried prior to collection.

Samples were analyzed for residues of thiabendazole and benzimidazole using a liquid chromatography method with tandem mass spectrometry detection (LC/MS/MS), Method GRM040.01A.  This method was previously reviewed by the Agency and was found to be acceptable for data collection (refer to 47705110.DER1, DP# 363974, 11/30/09, S. Hummel).  The limit of quantitation (LOQ; determined as the lowest level of method validation, LLMV) was 0.01 ppm for each analyte in each barley matrix, for a combined LOQ of 0.02 ppm.  The method was adequate for data collection based on acceptable concurrent recovery data.  The fortification levels used in concurrent method recovery were adequate to bracket expected residue levels.  Concurrent recoveries were corrected for apparent residues in controls; residues in the treated samples were not corrected for apparent residues in controls.  The method does not provide for conversion of residues of benzimidazole to parent equivalents.

Samples of barley were stored frozen (frozen at the field sites, <-10 °C at the preparation facility, ~-25 °C at the analytical laboratory) from collection to analysis for 69-354 days (2.3-11.6 months) for hay, 87-388 days (2.9-12.8 months) for grain, and 90-392 days (3.0-12.9 months) for straw.  Samples were generally analyzed within 0-21 days of extraction; one straw sample was re-analyzed within 76 days of extraction.  Acceptable storage stability data have been submitted demonstrating that residues of thiabendazole and benzimidazole in/on representative raw agricultural commodities are stable during frozen storage for up to ~10 months (refer to 48996712.der, interim report).  In addition, storage stability data are available indicating that residues of both analytes are stable during frozen storage for up to 23 months in/on wheat grain and straw (refer to the Residue Chemistry Chapter of the Thiabendazole RED; DP# 267871, 9/7/00, T. Morton) and for up to 22 months in/on soybean forage, hay, and seed (DP# 280701, 12/9/10, T. Morton).  These data are adequate to support the sample storage conditions and durations for the submitted study.

In barley grown from seed treated with the 4.1 lb ai/gal FS formulation of thiabendazole at 0.03-0.20 lb ai/A (34-224 g ai/ha), residues of benzimidazole were below the LOQ (<0.01 ppm) in/on all samples of barley hay and grain and straw harvested 52-242 and 83-256 DAP, respectively.   Residues (and per trial averages) of thiabendazole and combined residues of thiabendazole and benzimidazole, respectively, were:  <0.01-0.12 (<0.01-0.12) and <0.02-<0.13 (<0.02-<0.13) ppm in/on hay; <0.01-0.031 (<0.01-0.029) and <0.02-<0.041 (<0.02-<0.039) ppm in/on grain; and <0.01-0.085 (<0.01-0.082) and <0.02-<0.095 (<0.02-<0.092) ppm in/on straw.  There did not appear to be a correlation between the length of the treatment-to-planting interval and residue levels in this study.  Quantifiable residues of thiabendazole were observed in samples grown from seed planted 6, 15, 36, and 69  days after treatment.

NOTE:  The barley field trials reflect a shorter interval between treatment and planting than some of the other crop field trial studies submitted for thiabendazole.

Residue decline data were not submitted; however none are required because the pesticide is applied before the edible portion of the crop has formed.

Wheat.  Nineteen field trials were conducted in the United States during the 2011 growing season in the North American Free Trade Agreement (NAFTA) Growing Zones 2 (VA; 1 trial), 4 (MO; 1 trial), 5 (ND, MO, IA, and MN; 5 trials), 6 (TX; 1 trial), 7 (ND and NE; 4 trials), 8 (KS, TX, OK; 6 trials), and 11 (OR; 1 trial).  HED has determined that two trials (TK0050924-11 and TK0050924-12) should be considered replicates; the above field trial distribution incorporates this conclusion.

A flowable concentrate (water-dispersible suspension) for seed treatment (FS) formulation (Mertect(R) 340-F) containing 4.1 lb ai/gal thiabendazole was applied to wheat seed before planting.  The seed was treated at the SGS North America, Inc. facility (Brookings, SD) using commercial seed treatment procedures.  The test substance was applied to the seed using a Hege treater.  Application rates for thiabendazole were 0.08-0.14 lb ai/A (90-157 g ai/ha).  Application rates in lb ai/A were calculated by the petitioner from approximate seeding rate (seed/A) and actual seed treatment rate (mg ai/seed).  The nominal seed treatment rate was 0.03 mg ai/seed.  The seeding rate ranged from ~1,111,360-2,156,713 seed/A.  Composite seed samples from eight trials were shipped to SGS NAM GLP Laboratory (Brookings, SD) to confirm treatment rates.  Actual treatment rates were 94.9-107% of the target rate.  For each trial site, treated seed was planted within 4-96 days of treatment.  Samples of wheat forage, hay, and grain and straw, respectively, were harvested from all trials 39-236, 51-265, and 84-304 days after planting (DAP).  Hay samples were not dried prior to collection.

Samples were analyzed for residues of thiabendazole and benzimidazole using a liquid chromatography method with tandem mass spectrometry detection (LC/MS/MS), Method GRM040.01A.  This method was previously reviewed by the Agency and was found to be acceptable for data collection (refer to 47705110.DER1, DP# 363974, 11/30/09, S. Hummel).  The limit of quantitation (LOQ; determined as the lowest level of method validation, LLMV) was 0.01 ppm for each analyte in each wheat matrix, for a combined LOQ of 0.02 ppm.  The method was adequate for data collection based on acceptable concurrent recovery data.  The fortification levels used in concurrent method recovery were adequate to bracket expected residue levels.  Concurrent recoveries were corrected for apparent residues in controls; residues in the treated samples were not corrected for apparent residues in controls.  The method does not provide for conversion of residues of benzimidazole to parent equivalents.

Wheat samples were stored frozen (frozen at the field sites, <-10 °C at the preparation facility, -25 to -10 °C at the analytical laboratory) from collection to analysis for 61-353 days (2.0-11.6 months) for forage, 81-361 days (2.7-11.9 months) for hay, 59-359 days (1.9-11.8 months) for grain, and 58-323 days (1.9-10.6 months) for straw.  Samples were analyzed within 0-6 days of extraction.  Acceptable storage stability data have been submitted demonstrating that residues of thiabendazole and benzimidazole in/on representative raw agricultural commodities are stable during frozen storage for up to ~10 months (refer to 48996712.der, interim report).  In addition, storage stability data are available indicating that residues of both analytes are stable during frozen storage for up to 23 months in/on wheat grain and straw (refer to the Residue Chemistry Chapter of the Thiabendazole RED; DP# 267871, 9/7/00, T. Morton) and for up to 22 months in/on soybean forage, hay, and seed (DP# 280701, 12/9/10, T. Morton).  These data are adequate to support the sample storage conditions and durations for the submitted study.

In wheat grown from seed treated with the 4.1 lb ai/gal FS formulation of thiabendazole at 0.08-0.14 lb ai/A (90-157 g ai/ha), residues of thiabendazole and benzimidazole were each below the LOQ (<0.01 ppm) in/on wheat grain harvested 84-304 DAP; combined residues were <0.02 ppm in/on all samples of wheat grain.  Residues of benzimidazole were also below the LOQ in/on all samples of wheat forage, hay, and straw harvested 39-236, 51-265, and 84-304 DAP, respectively.   Residues (and per trial averages) of thiabendazole and combined residues of thiabendazole and benzimidazole, respectively, were:  <0.01-0.21 (<0.01-0.20) and <0.02-<0.22 (<0.02-<0.21) ppm in/on forage; <0.01-0.066 (<0.01-0.062) and <0.02-<0.076 (<0.02-<0.072) ppm in/on hay; and <0.01-0.078 (<0.01-0.073) and <0.02-<0.088 (<0.02-<0.083) ppm in/on straw, respectively.  There did not appear to be a correlation between the length of the treatment-to-planting interval and residue levels in this study.  Quantifiable residues of thiabendazole were observed in samples grown from seed planted 4 and 96 days after treatment as well as from seed planted at treatment-to-planting interval intervals of 14, 20-22, 43, 50-52, and 76 days.

NOTE:  The wheat field trials reflect a shorter interval between treatment and planting than some of the other crop field trial studies submitted for thiabendazole.

Residue decline data were not submitted; however none are required because the pesticide is applied before the edible portion of the crop has formed.

Root Vegetables (except sugar beet), subgroup 1B.  Field trials were conducted on carrot and radish.  Both radish roots and tops were analyzed.  Thirteen field trials were conducted in the United States during the 2011 growing season.  Eight carrot root trials were conducted in the North American Free Trade Agreement (NAFTA) Growing Zones 3 (FL; 1 trial), 5 (WI; 1 trial), 6 (TX; 1 trial), 10 (CA; 4 trials), and 11 (ID; 1 trial) and 5 radish root and tops trials were conducted in NAFTA Growing Zones 1 (NY; 1 trial), 3 (FL; 2 trials), 5 (IL; 1 trial), and 10 (CA; 1 trial).

Each trial consisted of one untreated plot and one treated plot.  For the treated plot, a flowable concentrate (water-dispersible suspension) for seed treatment (FS) formulation (Mertect(R) 340-F) containing 4.1 lb ai/gal thiabendazole was applied to carrot and radish seeds before planting.  The seeds were treated at the Syngenta Seeds facility (Stanton, MN) using commercial seed treatment procedures (slurry).  The test substance was applied to the seeds using a R6 or R12 treater.  Application rates for thiabendazole were 0.0003-0.007 lb ai/A (0.34-7.8 g ai/ha).  Application rates in lb ai/A were calculated by the petitioner from the approximate seeding rate (69,504-1,238,193 seed/A) and the actual seed treatment rate (0.0019-0.0024 mg ai/seed).  The nominal seed treatment rate was 0.002 mg ai/seed.  Composite control and treated seed samples were shipped to SGS NAM GLP Laboratory (Brookings, SD) to confirm treatment rates.  Actual treatment rates were 96-120% of the target rate.  Samples of treated seed were planted within 5-148 days after treatment.  Single control and duplicate treated samples of carrot roots and radish roots and tops were collected at normal commercial harvest 79-134 and 26-60 days after planting (DAP), respectively.

Carrot root and radish root and top samples were analyzed for residues of thiabendazole and its metabolite using high performance liquid chromatography with tandem mass spectrometry detection (LC/MS/MS); Syngenta Method GRM040.01A.  This method was previously reviewed by the Agency and was found to be acceptable for data collection (refer to 47705110.DER1, DP# 363974, 11/30/09, S. Hummel).  The limit of quantitation (LOQ; determined as the lowest limit of method validation, LLMV) was 0.01 ppm for each analyte in each matrix, for a combined LOQ of 0.02 ppm.  The method was adequate for data collection based on acceptable concurrent recovery data.  The fortification levels used in concurrent method recovery were adequate to bracket expected residue levels.  Concurrent recoveries were corrected for apparent residues in controls; residues in the treated samples were not corrected for apparent residues in controls.  The method does not provide for conversion of residues of benzimidazole to parent equivalents.

Samples were stored frozen (frozen at the field sites, <-10 °C at the preparation facility, and
< -20 °C at the analytical laboratory) from collection to analysis for 90-257 days (3.0-8.5 months) for carrot roots and 157-290 days (5.2-9.5 months) for radish roots and tops.  All samples were analyzed within 2-4 days of extraction.  Acceptable storage stability data have been submitted demonstrating that residues of thiabendazole and benzimidazole in/on representative raw agricultural commodities are stable during frozen storage for up to ~10 months (refer to 48996712.der, interim report).  These data are adequate to support the sample storage conditions and durations for the submitted study.

In crops grown from seed treated with the 4.1 lb ai/gal FS formulation of thiabendazole at 0.0003-0.007 lb ai/A (0.34-7.8 g ai/ha), residues of thiabendazole and benzimidazole were each below the LOQ (<0.01) ppm in/on all samples of carrot roots and radish roots and tops harvested at 79-134 and 26-60 DAP, respectively; combined residues were <0.02 ppm in/on all samples.

Residue decline data were not submitted; however none are required because the pesticide is applied before the edible portion of the crop has formed.

Brassica Head and Stem Vegetables, subgroup 5A.  Twelve field trials were conducted in the United States during the 2010 growing season.  Six cabbage trials were conducted in the North American Free Trade Agreement (NAFTA) Growing Zones 1 (NY; 1 trial), 2 (NC; 1 trial), 3 (FL; 1 trial), 5 (ND; 1 trial), 6 (TX; 1 trial), and 10 (CA; 1 trial), and six broccoli field trials were conducted in NAFTA Growing Zones 6 (TX; 1 trial), 10 (CA; 4 trials), and 12 (OR; 1 trial).

A flowable concentrate (water-dispersible suspension) for seed treatment (FS) formulation (Mertect(R) 340-F) containing 4.1 lb ai/gal thiabendazole was applied to cabbage and broccoli seed before planting.  The seed was treated at the Syngenta Seeds facility (Stanton, MN) using commercial seed treatment procedures.  The test substance was applied to the seed using a Roto Stat R-12.  Application rates for thiabendazole were 0.00019-0.0008 lb ai/A (0.21-0.90 g ai/ha).  Application rates in lb ai/A were calculated by the petitioner from approximate seeding rate (seed/A) and actual seed treatment rate (mg ai/seed).  The nominal seed treatment rate was 0.002 mg ai/seed.  The seeding rate ranged from ~11,600 seed/A to 217,800 seed/A.  In two field trials (NY and ND), the seed verification samples were lost in transit, and the actual seed treatment rates were not reported.  For these trials the petitioner reported the nominal application rates (0.004-0.008 lb ai/A; 0.11-0.90 g ai/ha).  Composite seed samples were shipped to SGS NAM GLP Laboratory (Brookings, SD) to confirm treatment rates.  Actual treatment rates were 70-130% of the target rate.  For each trial site, treated seed was planted within 1-163 days of treatment.  Samples of cabbage heads with wrapper leaves and broccoli head and stem were harvested from all trials 73-190 days after planting (DAP).
Samples were analyzed for residues of thiabendazole and benzimidazole using a liquid chromatography method with tandem mass spectrometry detection (LC/MS/MS), Method GRM040.01A.  This method was previously reviewed by the Agency and was found to be acceptable for data collection (refer to 47705110.DER1, DP# 363974, 11/30/09, S. Hummel).  The limit of quantitation (LOQ; determined as the lowest level of method validation, LLMV) was 0.01 ppm for each analyte, for a combined LOQ of 0.02 ppm.  The method was adequate for data collection based on acceptable concurrent recovery data.  The fortification levels used in concurrent method recovery were adequate to bracket expected residue levels.  Concurrent recoveries were corrected for apparent residues in controls; residues in the treated samples were not corrected for apparent residues in controls.  The method does not provide for conversion of residues of benzimidazole to parent equivalents.

Samples were stored frozen (frozen at the field sites, <-10 °C at the preparation facility, ~ -20 °C at the analytical laboratory) from collection to analysis for 124-300 days (4.1-9.9 months) for cabbage and 93-308 days (3.1-10.1 months) for broccoli.  Samples were analyzed within 1-4 days of extraction.  Acceptable storage stability data have been submitted demonstrating that residues of thiabendazole and benzimidazole in/on representative raw agricultural commodities are stable during frozen storage for up to ~10 months (refer to 48996712.der, interim report).  In addition, storage stability data are available indicating that residues of both analytes are stable during frozen storage for up to 28 months in/on whole potato and wet peel (refer to the Residue Chemistry Chapter of the Thiabendazole RED; DP# 267871, 9/7/00, T. Morton) and for up to 22 months in/on soybean forage, hay, and seed (DP# 280701, 12/9/10, T. Morton).  These data are adequate to support the sample storage conditions and durations for the submitted study.

In cabbage and broccoli grown from seed treated with the 4.1 lb ai/gal FS formulation of thiabendazole at 0.00019-0.0008 lb ai/A (0.21-0.90 g ai/ha), residues of thiabendazole and benzimidazole were each below the LOQ (<0.01 ppm) in/on all samples harvested 73-190 DAP; combined residues were <0.02 ppm in/on all samples.

Residue decline data were not submitted; however none are required because the pesticide is applied before the edible portion of the crop has formed.

Spinach.  Eight field trials were conducted in the United States during the 2010-2011 growing seasons in the North American Free Trade Agreement (NAFTA) Growing Zones 1 (NJ; 1 trial), 2 (GA; 2 trials), 6 (TX; 2 trials), 8 (CO; 1 trial), and 10 (CA; 2 trials).

A flowable concentrate (water-dispersible suspension) for seed treatment (FS) formulation (Mertect(R) 340-F) containing 4.1 lb ai/gal thiabendazole was applied to spinach seeds before planting.  The seeds were treated at the Syngenta Seeds facility (Stanton, MN) using commercial seed treatment procedures.  The test substance was applied to the seeds using a Roto Stat R-12.  Application rates for thiabendazole were 0.001-0.014 lb ai/A (0.8-15.7 g ai/ha).  Application rates in lb ai/A were calculated by the petitioner from the approximate seeding rate (52,272-1,045,440 seed/A) and actual seed treatment rates (0.006-0.007 mg ai/seed).  The nominal seed treatment rate was 0.006 mg ai/seed.  Composite seed samples were shipped to SGS NAM GLP Laboratory (Brookings, SD) to confirm treatment rates.  Actual treatment rates were 100-117% of the target rate.  For each trial site, samples of treated seeds were planted within 48-237 days of treatment.  Samples of spinach leaves were harvested from all trials at 47- to 89-days after planting (DAP).  Additionally, samples of immature (baby) spinach leaves were harvested from two sites at 43-54 DAP.

Samples were analyzed for residues of thiabendazole and benzimidazole using a liquid chromatography method with tandem mass spectrometry detection (LC/MS/MS), Method GRM040.01A.  This method was previously reviewed by the Agency and was found to be acceptable for data collection (refer to 47705110.DER1, DP# 363974, 11/30/09, S. Hummel).  The limit of quantitation (LOQ; determined as the lowest level of method validation, LLMV) was 0.01 ppm for each analyte, for a combined LOQ of 0.02 ppm.  The method was adequate for data collection based on acceptable concurrent recovery data.  The fortification levels used in concurrent method recovery were adequate to bracket expected residue levels.  Concurrent recoveries were corrected for apparent residues in controls; residues in the treated samples were not corrected for apparent residues in controls.  The method does not provide for conversion of residues of benzimidazole to parent equivalents.

Samples were stored frozen (frozen at the field sites, <-10 °C at the preparation facility, ~ -20 °C at the analytical laboratory) from collection to analysis for 43-248 days (1.4-8.2 months).  All samples were analyzed within 2-3 days of extraction.  Acceptable storage stability data have been submitted demonstrating that residues of thiabendazole and benzimidazole in/on representative raw agricultural commodities are stable during frozen storage for up ~10 months (refer to 48996712.der, interim report).  These data are considered adequate to support the sample storage durations for the submitted study.  We note that the study indicated that residues of benzimidazole may decline slightly in/on spinach during frozen storage (corrected recovery of ~66% at 9 months).  HED does not believe this potential loss on storage would have any appreciable effect on the residue results.

In crops grown from seed treated with the 4.1 lb ai/gal FS formulation of thiabendazole at 0.001-0.014 lb ai/A (1.3-15.7 g ai/ha), residues of thiabendazole and benzimidazole were each below the LOQ (<0.01 ppm) in/on all samples of mature and immature spinach leaves harvested 43-89 DAP; combined residues were <0.02 ppm in/on all samples.

Residue decline data were not submitted; however none are required because the pesticide is applied before the edible portion of the crop has formed.

Soybeans.  Additional data were required for thiabendazole in the RED.  Additionally,  Syngenta Crop Protection, LLC has requested an amendment to the registration for Mertect(R) 340-F, containing 4.1 lb ai/gal thiabendazole to increase the application rate for soybean seed treatment.   Syngenta Crop Protection, LLC has submitted field trial data for thiabendazole on soybean.  Nineteen field trials were conducted in the United States during the 2010 growing season in the North American Free Trade Agreement (NAFTA) Growing Zones 2 (SC and NC; 2 trials), 4 (LA; 3 trials), and 5 (ND, SD, IA, OH, MO, WI, NE, and MN; 14 trials).  HED has determined that two trials (C01-0599 and C01-0607) should be considered replicates; the above field trial distribution incorporates this conclusion.

A flowable concentrate (water-dispersible suspension) for seed treatment (FS) formulation (Mertect(R) 340-F) containing 4.1 lb ai/gal thiabendazole was applied to wheat seeds before planting.  The seeds were treated at the SGS North America, Inc. facility (Brookings, SD) using commercial seed treatment procedures.  The test substance was applied to the seeds using a Hege treater.  Application rates for thiabendazole were 0.012-0.024 lb ai/A (13.5-26.9 g ai/ha).  Application rates in lb ai/A were calculated by the petitioner from approximate seeding rates (78,400-169,061 seed/A) and actual seed treatment rates (0.052-0.069 mg ai/seed), equivalent to 2x the requested amended applicatioin rate.  The nominal seed treatment rate, calculated by the study reviewer, was 0.06 mg ai/seed, based on a treatment rate of 40 g ai/100 kg seed and 3,000 seeds/lb.  Composite seed samples were shipped to SGS NAM GLP Laboratory (Brookings, SD) to confirm treatment rates.  Actual treatment rates were 91-106% of the target rate.  For each trial site, samples of treated seeds were planted within 3-30 days of treatment.  Samples of soybean forage and hay were harvested from all trials 46-94 days after planting (DAP); seed was harvested 109-153 DAP.  Hay samples were dried to approximately 10-20% moisture content; drying intervals were not reported.

Samples were analyzed for residues of thiabendazole and benzimidazole using a liquid chromatography method with tandem mass spectrometry detection (LC/MS/MS), Method GRM040.01A.  This method was previously reviewed by the Agency and was found to be acceptable for data collection (refer to 47705110.DER1, DP# 363974, 11/30/09, S. Hummel).  The limit of quantitation (LOQ; determined as the lowest level of method validation, LLMV) was 0.01 ppm for each analyte in each soybean matrix, for a combined LOQ of 0.02 ppm.  The method was adequate for data collection based on acceptable concurrent recovery data.  The fortification levels used in concurrent method recovery were adequate to bracket expected residue levels.  Concurrent recoveries were corrected for apparent residues in controls; residues in the treated samples were not corrected for apparent residues in controls.  The method does not provide for conversion of residues of benzimidazole to parent equivalents.

Samples of soybean were stored frozen (frozen at the field sites, <-10 °C at the preparation facility, ~ -20 °C at the analytical laboratory) from collection to analysis for 221-273 days (7.3-9.0 months) for forage, 222-274 days (7.3-9.0 months) for hay, and 181-224 days (6.0-7.4 months) for seed.  Samples were analyzed within 1-7 days of extraction.  Acceptable storage stability data are available indicating that residues of both analytes are stable during frozen storage for up to 22 months in/on soybean forage, hay, and seed (DP# 280701, 12/9/10, T. Morton).  These data are adequate to support the sample storage conditions and durations for the submitted study.

In crops grown from seed treated with the 4.1 lb ai/gal FS formulation of thiabendazole at 0.012-0.024 lb ai/A (13.5-26.9 g ai/ha), residues of thiabendazole and benzimidazole were each below the LOQ (<0.01 ppm) in/on all samples of soybean forage and hay harvested 46-94 DAP and soybean seed harvested 109-153 DAP; combined residues were <0.02 ppm in/on all samples.

Residue decline data were not submitted; however none are required because the pesticide is applied before the edible portion of the crop has formed.

Dry Bulb Onions.  Eight field trials were conducted in the United States during the 2010-2011 growing seasons in the North American Free Trade Agreement (NAFTA) Growing Zones 1 (NY; 1 trial), 5 (IA; 1 trial), 6 (TX; 1 trial), 8 (TX; 1 trial), 10 (CA; 2 trials), 11 (ID; 1 trial), and 12 (OR; 1 trial).

A flowable concentrate (water-dispersible suspension) for seed treatment (FS) formulation (Mertect(R) 340-F) containing 4.1 lb ai/gal thiabendazole was applied to dry bulb onion seeds before planting.  The seeds were treated at the Syngenta Seeds facility (Stanton, MN) using commercial seed treatment procedures.  The test substance was applied to the seeds using a Roto Stat R-12.  Application rates for thiabendazole were 0.001-0.003 lb ai/A (1.1-3.4 g ai/ha).  Application rates in lb ai/A were calculated by the petitioner from the approximate seeding rate (52,800-620,000 seed/A) and actual seed treatment rates (0.002-0.005 mg ai/seed).  The nominal seed treatment rate was 0.002 mg ai/seed.  Composite seed samples were shipped to SGS NAM GLP Laboratory (Brookings, SD) to confirm treatment rates.  Actual treatment rates were 105-250% of the target rate.  For each trial site, samples of treated seeds were planted within 8-323 days of treatment.  Samples of dry bulb onions were harvested from all trials 113-252 days after planting (DAP).

Samples were analyzed for residues of thiabendazole and benzimidazole using a liquid chromatography method with tandem mass spectrometry detection (LC/MS/MS), Method GRM040.01A.  This method was previously reviewed by the Agency and was found to be acceptable for data collection (refer to 47705110.DER1, DP# 363974, 11/30/09, S. Hummel).  The limit of quantitation (LOQ; determined as the lowest level of method validation, LLMV) was 0.01 ppm for each analyte, for a combined LOQ of 0.02 ppm.  The method was adequate for data collection based on acceptable concurrent recovery data.  The fortification levels used in concurrent method recovery were adequate to bracket expected residue levels.  Concurrent recoveries were corrected for apparent residues in controls; residues in the treated samples were not corrected for apparent residues in controls.  The method does not provide for conversion of residues of benzimidazole to parent equivalents.

Samples were stored frozen (frozen at the field sites, <-10 °C at the preparation facility, ~ -20 °C at the analytical laboratory) from collection to analysis for 73-140 days (2.4-4.6 months).  All samples were analyzed within 1-2 days of extraction.  Acceptable storage stability data have been submitted demonstrating that residues of thiabendazole and benzimidazole in/on representative raw agricultural commodities are stable during frozen storage for up to ~10 months (refer to 48996712.der, interim report).  These data are considered adequate to support the sample storage durations for the submitted study.

In crops grown from seed treated with the 4.1 lb ai/gal FS formulation of thiabendazole at 0.001-0.003 lb ai/A (1.1-3.4 g ai/ha), residues of thiabendazole and benzimidazole were each below the LOQ (<0.01 ppm) in/on all samples of dry bulb onion harvested 113-252 DAP; combined residues were <0.02 ppm in/on all samples.

Residue decline data were not submitted; however none are required because the pesticide is applied before the edible portion of the crop has formed.

TABLE 5.	Summary of Residue Data with Thiabendazole.
Commodity
                                    Analyte
                                  Total Rate
                                    lb ai/A
                                  (g ai/ha)
                                      DAP
                                    (days)
                            Residue Levels (ppm)[1]

                                       n
                                  Sample Min.
                                  Sample Max.
                                    LAFT[2]
                                    HAFT[2]
                                    Median
                                     Mean
                                   Std. Dev.
Alfalfa Forage -1[st] Cutting
                                 Thiabendazole
                                   0.02-0.05
                                    (22-56)
                                    45-253
                                      12
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                      12
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                      12
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Alfalfa Forage  -  2[nd] Cutting
                                 Thiabendazole
                                   0.02-0.05
                                    (22-56)
                                    70-292
                                      12
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                      12
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                      12
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Alfalfa Forage  -  3[rd] Cutting
                                 Thiabendazole
                                   0.02-0.05
                                    (22-56)
                                    110-323
                                      10
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                      10
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                      10
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Alfalfa Hay  -  1[st] Cutting
                                 Thiabendazole
                                   0.02-0.05
                                    (22-56)
                                    42-253
                                      12
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                      12
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                      12
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Alfalfa Hay  -  2[nd] Cutting
                                 Thiabendazole
                                   0.02-0.05
                                    (22-56)
                                    70-292
                                      12
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                      12
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                      12
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Alfalfa Hay  -  3[rd] Cutting
                                 Thiabendazole
                                   0.02-0.05
                                    (22-56)
                                    110-323
                                      10
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                      10
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                      10
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Alfalfa Seed
                                 Thiabendazole
                                  0.003-0.04
                                   (3.4-45)
                                    185-374
                                       2
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                       2
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                       2
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Barley Hay
                                 Thiabendazole
                                   0.03-0.20
                                    52-242
                                      12
                                   <0.01
                                     0.12
                                   <0.01
                                     0.12
                                     0.010
                                     0.023
                                     0.032

                                 Benzimidazole

                                      12
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                      12
                                   <0.02
                                   <0.13
                                   <0.02
                                   <0.13
                                     0.020
                                     0.033
                                     0.032
Barley Grain
                                 Thiabendazole
                                   0.03-0.20
                                    83-256
                                      12
                                   <0.01
                                     0.031
                                   <0.01
                                     0.029
                                     0.010
                                     0.012
                                     0.005

                                 Benzimidazole

                                      12
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                      12
                                   <0.02
                                   <0.041
                                   <0.02
                                   <0.039
                                     0.020
                                     0.022
                                     0.005
Barley Straw
                                 Thiabendazole
                                   0.03-0.20
                                    83-256
                                      12
                                   <0.01
                                     0.085
                                   <0.01
                                     0.082
                                     0.010
                                     0.024
                                     0.024

                                 Benzimidazole

                                      12
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                      12
                                   <0.02
                                   <0.095
                                   <0.02
                                   <0.092
                                     0.020
                                     0.034
                                     0.024
Wheat Forage
                                 Thiabendazole
                                   0.08-0.14
                                   (90-157)
                                    39-236
                                      19
                                   <0.01
                                     0.21
                                   <0.01
                                     0.20
                                     0.010
                                     0.025
                                     0.044

                                 Benzimidazole

                                      19
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                      19
                                   <0.02
                                   <0.22
                                   <0.02
                                   <0.21
                                     0.020
                                     0.035
                                     0.044
Wheat Hay
                                 Thiabendazole
                                   0.08-0.14
                                   (90-157)
                                    51-265
                                      19
                                   <0.01
                                     0.066
                                   <0.01
                                     0.062
                                     0.010
                                     0.015
                                     0.015

                                 Benzimidazole

                                      19
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                      19
                                   <0.02
                                   <0.076
                                   <0.02
                                   <0.072
                                     0.020
                                     0.025
                                     0.015
Wheat Grain
                                 Thiabendazole
                                   0.08-0.14
                                   (90-157)
                                    84-304
                                      19
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                      19
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                      19
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Wheat Straw
                                 Thiabendazole
                                   0.08-0.14
                                   (90-157)
                                    84-304
                                      19
                                   <0.01
                                     0.078
                                   <0.01
                                     0.073
                                     0.010
                                     0.014
                                     0.015

                                 Benzimidazole

                                      19
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                      19
                                   <0.02
                                   <0.088
                                   <0.02
                                   <0.083
                                     0.020
                                     0.024
                                     0.015
Carrot roots
                                 Thiabendazole
                                 0.0003-0.007
                                  (0.34-7.8)
                                    79-134
                                       8
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                       8
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                       8
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Radish roots
                                 Thiabendazole
                                  0.002-0.004
                                   (2.2-4.5)
                                     26-60
                                       5
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                       5
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                       5
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Radish tops
                                 Thiabendazole
                                  0.002-0.004
                                   (2.2-4.5)
                                     26-60
                                       5
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                       5
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                       5
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Cantaloupe
                                 Thiabendazole
                                  0.002-0.008
                                   (2.2-9.0)
                                    62-119
                                       6
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                       6
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                       6
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Cucumber
                                 Thiabendazole
                                  0.005-0.012
                                  (5.6-13.4)
                                     49-81
                                       6
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                       6
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                       6
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Summer
Squash
                                 Thiabendazole
                                  0.001-0.007
                                   (1.1-7.8)
                                     33-62
                                       5
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                       5
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                       5
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Cabbage heads w/wrapper leaves
                                 Thiabendazole
                                0.00025-0.00077
                                (0.28-0.86)[4]
                                    84-190
                                       6
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                       6
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                       6
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Broccoli head and stem
                                 Thiabendazole
                                0.00019-0.0008
                                  (0.21-0.90)
                                    73-137
                                       6
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                       6
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                       6
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Spinach Leaves
                                 Thiabendazole
                                  0.001-0.014
                                  (0.8-15.7)
                                     47-89
                                       8
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                       8
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                       8
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Immature (Baby) Spinach Leaves
                                 Thiabendazole
                                  0.001-0.014
                                  (0.8-15.7)
                                     43-54
                                       2
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                       2
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                       2
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Soybean Forage
                                 Thiabendazole
                                  0.012-0.024
                                  (13.5-26.9)
                                     46-94
                                      19
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                      19
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                      19
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Soybean Hay
                                 Thiabendazole
                                  0.012-0.024
                                  (13.5-26.9)
                                     46-94
                                      19
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                      19
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                      19
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Soybean Seed
                                 Thiabendazole
                                  0.012-0.024
                                  (13.5-26.9)
                                    109-153
                                      19
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                      19
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                      19
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
Dry Bulb Onion
                                 Thiabendazole
                                  0.001-0.003
                                   (1.1-3.4)
                                    113-252
                                       8
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                                 Benzimidazole

                                       8
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01
                                     0.01
                                     0.01
                                      N/A

                             Combined Residues[3]

                                       8
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                     0.02
                                     0.02
                                      N/A
[1]  Except for sample min/max, values reflect per trial averages; n = no. of field trials.  N/A = Not Applicable
[2]  LAFT = lowest average field trial; HAFT = highest average field trial.
3  Combined residues of thiabendazole and benzimidazole.  Residues of benzimidazole were not converted to parent equivalents.

Conclusions. The submitted field trial data are adequate to support the tolerance request and amended registration request.  Acceptable methods were used for residue quantitation, and the study is supported by adequate storage stability data.

860.1520 Processed Food and Feed
48996703	Wheat Processing
48996709	 Soybean processing

Wheat Processing.  Syngenta Crop Potection, LLC has submitted a processing study for thiabendazole and benzimidazole in/on wheat grain.  In one trial conducted in Campbell, MN, and one trial conducted in Hinton, OK, a flowable concentrate (water-dispersible suspension) for seed treatment (FS) formulation (Mertect(R) 340-F) containing 4.1 lb /gal thiabendazole was applied to wheat seeds before planting. The seeds were treated at SGS North America, Inc. (Brookings, SD) using commercial seed treatment procedures.  A Hege seed treater was used to apply an exaggerated rate (5x field rate) of 0.47-0.71 lb ai/A (529-791 g ai/ha).  Application rates in lb ai/A were calculated by the petitioner from approximate seeding rate (1,530,350  -  2,065,631 seed/A) and actual seed treatment rate (0.14-0.16 mg ai/seed); 5x the nominal seed treatment rate of 0.03 mg ai/seed..  The nominal application rate was 0.15 mg ai/seed.  Composite seed samples were shipped to SGS NAM GLP Laboratory (Brookings, SD) to confirm treatment rates.  Actual treatment rates for wheat seeds associated with the processing study (exaggerated application rate) were 95.5-103% of the target rate.  Treated wheat seeds were planted with 8-43 days of treatment.  At the end of the growing season, wheat grain was harvested at crop maturity 98-216 days after planting (DAP) and processed into bran, flour, middlings, shorts and germ using simulated commercial procedures.  Processing was conducted by GLP Technologies (Navasota, TX).  Adequate descriptions of the processing procedures were provided, including material balance summaries.

Samples were analyzed for residues of thiabendazole and metabolite benzimidazole using a liquid chromatography method with tandem mass spectrometric detection (LC/MS/MS), Method GRM040.01A. This method was previously reviewed by the Agency and was found to be acceptable for data collection (refer to 47705110.DER1, DP# 363974, 11/30/09, S. Hummel). The limit of quantitation (LOQ; determined as the lowest level of method validation, LLMV) was 0.01 ppm for each analyte, for an LOQ of 0.02 ppm for combined residues.  The method was adequate for data collection based on acceptable concurrent recovery data.  The fortification levels used in concurrent method recovery were adequate to bracket expected residue levels.  Concurrent recoveries were corrected for apparent residues in controls; residues in the treated samples were not corrected for apparent residues in controls.  The method does not provide for conversion of residues of benzimidazole to parent equivalents.

Samples were stored under ambient conditions (field sites) and frozen (generally <-10 °C at the processing facility, preparation facility, and analytical laboratory) from harvest/processing to analysis.  Processing took place within 71-378 days of harvest.  Sample analyses were completed within 129-414 days (4.2-13.6 months) of harvest for grain (RAC) and within 39-96 days (1.3-3.2 months) of processing for the processed commodities.  All samples were analyzed within 2-5 days of extraction.  Acceptable storage stability data have been submitted demonstrating that residues of thiabendazole and benzimidazole in/on representative raw agricultural commodities are stable during frozen storage for up to ~10 months (refer to 48996712.der, interim results).  In addition, storage stability data are available indicating that residues of both analytes are stable during frozen storage for up to 23 months in/on wheat grain and for up to 18 months in wheat bran, and flour (refer to DP# 267871, 9/7/00, T. Morton). These data are adequate to support the sample storage conditions and durations for the submitted study.
In crops grown from seed treated with the 4.1 lb ai/gal FS formulation of thiabendazole at 0.47-0.71 lb ai/A (529-791 g ai/ha), residues of thiabendazole and benzimidazole were below the LOQ (<0.01 ppm for each analyte, <0.02 ppm for combined residues) in/on all samples of wheat grain (RAC) and processed commodities (bran, flour, middlings, shorts, and germ); therefore, processing factors were not calculated.

The maximum theoretical concentration factor for wheat is 8x for wheat (OCSPP 860.1520, Table 1). Theoretical concentration factors are 7.7x for bran, 1.4x for flour, and 8.3x for shorts (based on separation into components; OCSPP 860.1520, Table 3).

Soybean Processing.  Syngenta Crop Potection, LLC has submitted a processing study for thiabendazole and benzimidazole in/on soybean seeds.  In one trial conducted in Richland, IA, and one trial conducted in Marysville, OH, a flowable concentrate (water-dispersible suspension) for seed treatment (FS) formulation (Mertect(R) 340-F) containing 4.1 lb thiabendazole/gal was applied to soybean seeds before planting. The seeds were treated at SGS North America, Inc. (Brookings, SD) using commercial seed treatment procedures.  A Hege seed treater was used to apply the test substance at an exaggerated rate (5x field rate of the concurrent field trial study) of 0.09 lb ai/A (100.9 g ai/ha).  Application rates in lb ai/A were calculated by the petitioner from the approximate seeding rates (138,000 - 148,459 seed/A) and the actual seed treatment rate (0.29 mg ai/seed).  The nominal seed treatment rate was 0.31 mg ai/seed, based on a treatment rate of 200 g ai/100 kg seed and 3,000 seeds/lb.  Composite seed samples were shipped to SGS NAM GLP Laboratory (Brookings, SD) to confirm treatment rates.  The actual seed treatment rate was 104% of the target rate.  Treated soybean seeds were planted with 8-20 days of treatment.  At the end of the growing season, soybean seeds were harvested at crop maturity 126-130 days after planting (DAP) and processed into meal, hulls, refined oil, flour, milk, tofu, soy sauce, miso, pollard and crude oil using simulated commercial procedures.  Processing was conducted by GLP Technologies (Navasota, TX).  Adequate descriptions of the processing procedures were provided, including material balance summaries.

Samples were analyzed for residues of thiabendazole and metabolite benzimidazole using a liquid chromatography method with tandem mass spectrometric detection (LC/MS/MS), Method GRM040.01A. This method was previously reviewed by the Agency and was found to be acceptable for data collection (refer to 47705110.DER1, DP# 363974, 11/30/09, S. Hummel). The limit of quantitation (LOQ; determined as the lowest level of method validation, LLMV) was 0.01 ppm for each analyte, for an LOQ of 0.02 ppm for combined residues.  The method was adequate for data collection based on acceptable concurrent recovery data.  The fortification levels used in concurrent method recovery were adequate to bracket expected residue levels.  Concurrent recoveries were corrected for apparent residues in controls; residues in the treated samples were not corrected for apparent residues in controls.  The method does not provide for conversion of residues of benzimidazole to parent equivalents.

Samples of soybean seeds were shipped directly from each field site to the processing facility under ambient or frozen conditions within 0-5 days of harvest.  Samples were stored frozen at the processing and preparation facilities (<-10 °C) and at the analytical laboratory (~-20 °C). Processing was completed within 14-41 days of harvest for all commodities, except for soy sauce and miso which was completed within 248-264 days of harvest due to a ~6 month processing time.  Sample analyses were completed within 109-125 days (3.6-4.1 months) of harvest for seed (RAC) and within 33-94 days (1.1-3.1 months) of processing for the processed commodities.  All samples were analyzed within 1-7 days of extraction.  Adequate storage stability data are available indicating that residues of both analytes are stable during frozen storage for up to 22 months in/on soybean forage, hay, and seed (DP# 280701, 12/9/10, T. Morton).  In addition, storage stability data are available indicating that residues of both analytes are stable during frozen storage for up to 12 months in soybean oil (refer to 48996712.der, interim results) and for up to 18 months in wheat bran and flour (refer to the Residue Chemistry Chapter of the Thiabendazole RED; DP# 267871, 9/7/00, T. Morton).  These data are adequate to support the sample storage conditions and durations for the submitted study.

In crops grown from seed treated with the 4.1 lb ai/gal FS formulation of thiabendazole at 0.09 lb ai/A (100.9 g ai/ha), residues of thiabendazole and benzimidazole were below the LOQ (<0.01 ppm for each analyte, <0.02 ppm for combined residues) in/on all samples of soybean seed (RAC) and processed commodities (meal, hulls, refined oil, flour, milk, tofu, soy sauce, miso, pollard and crude oil); therefore, processing factors were not calculated.

The maximum theoretical concentration factor for soybean is 12x (OCSPP 860.1520, Table 1). Theoretical concentration factors are 11.3x for hulls, 2.2x for meal and 12.0x for oil (based on separation into components; OCSPP 860.1520, Table 3).

TABLE 6.	Residue Data from Wheat Processing Studies with Thiabendazole and Benzimidazole.
RAC
                              Processed Commodity
                                 Total Rate[1]
                                    lb ai/A
                                   (g ai/ha)
                                    DAP[2]
                         Residues (ppm), [Average][3]
                             Processing Factor[4]

                                 Thiabendazole
                                 Benzimidazole
                                  Combined[5]
                                   Thiaben-
                                    dazole
                                Benzimi-dazole
                                  Combined[5]
                       Campbell, MN; 2011 (TK0050924-19)
Wheat
                              Pre-processed Grain
                                     (RAC)