![](media/image1.png){width="0.8in" height="0.8in"} **UNITED STATES
ENVIRONMENTAL PROTECTION AGENCY**

WASHINGTON, D.C. 20460

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| OFFICE OF                                                             |
|                                                                       |
| PREVENTION, PESTICIDES,                                               |
|                                                                       |
| AND TOXIC SUBSTANCES                                                  |
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**[MEMORANDUM]{.underline}**

Date: October 14, 2005

Subject: Triadimenol. Registrants Response to Residue Chemistry Data
Requirements.

Field Corn, Cotton, and Wheat Processing Studies.

DP Barcode: D322336 PC Code: 127201

40 CFR §: 180.410 Chemical Class: Azole

MRID Numbers: 44519801, 44519802, and 44519803

From: Samuel Ary, Chemist

Reregistration Branch II

Health Effects Division (7509C)

Through: Yvonne Barnes, Chemist

Reregistration Branch II

Health Effects Division (7509C)

William Hazel, Branch Chief

Reregistration Branch II

Health Effects Division (7509C)

To: Richard Griffin, Risk Assessor

Reregistration Branch II

Health Effects Division (7509C)

John Pates, Chemical Review Manager

Reregistration Branch I

Special Review and Reregistration Division (7508C)

This document was originally prepared under contract by Dynamac
Corporation (2275 Research Boulevard, Rockville, MD 20850; submitted
August 16, 2000). The document has been reviewed by the Health Effects
Division (HED) and revised to reflect current Office of Pesticide
Program (OPP) policies.

[INTRODUCTION]{.underline}

In response to the Triadimenol Data Call-In (3/8/1996), Gustafson, Inc,
has submitted data pertaining to the magnitude of triadimenol residues
of concern in the processed commodities of field corn (1998; MRID
44519801), cotton (1998; MRID 44519802) and wheat (1998; MRID 44519803).
These data are evaluated in this document for adequacy in fulfilling
residue chemistry data requirements.

Triadimenol,
-(4-chlorophenoxy)\--(1,1-dimethylethyl)-1H-1,2,4-triazole-1-ethanol, is
a systemic fungicide registered for use in the United States as a seed
treatment for barley, corn, cotton, oats, rye, sorghum, and wheat.
Additionally, an import tolerance on bananas has been established.
Triadimenol end-use products are marketed in the U.S. under the trade
name Baytan^®^. The reregistration of triadimenol is being supported by
Bayer CropScience (Bayer), the basic producer. The triadimenol
formulations registered for food/feed uses include wettable powder (WP),
flowable concentrate (FlC), emulsifiable concentrate (EC), and soluble
concentrate (SC) formulations.

Tolerances are established for residues of triadimenol and
1-(4-chlorophenoxy)-3,3-dimethyl-3-
hydroxymethyl-1-(1H-1,2,4-triazol-1-yl)-2-butanol (KWG 1342; calculated
as triadimenol) in/on various plant commodities \[40 CFR §180.450(a)\].
The established tolerances for plant commodities range from 0.01 ppm
(sorghum grain and fodder) to 2.5 ppm (green forage of oats, rye, and
wheat). Tolerances are established for residues of triadimenol and its
metabolites containing the chlorophenoxy moiety (calculated as
triadimenol) in/on livestock commodities at 0.01 ppm (milk, and poultry
commodities) and 0.1 ppm (fat, meat, and meat byproducts of cattle,
goats, hogs, horses, and sheep).

Triadimenol and its butanediol metabolite (KWG 1342) are also regulated
as metabolites of the fungicide triadimefon (40 CFR §180.410).

The reregistration requirements for plant metabolism have not been
fulfilled. No metabolism studies with triadimenol have been submitted;
however, metabolism studies with triadimefon have been received and
reviewed. The Health Effects Division (HED) has examined the results of
these studies and determined that the triadimefon residues of concern
in/on apples, grapes, pears, pineapples, and raspberries for tolerance
expression are triadimefon and triadimenol and for risk assessment are
triadimefon, triadimenol, KWG 1323 \[1-(4-chlorophenoxy)-3,3-dimethyl-
3-hydroxymethyl-1-(1H-1,2,4-triazol-1-yl)-2-butanone\], and KWG 1342 (S.
Ary, D314742, 11/23/2005). Of these compounds, triadimenol and KWG 1342
are currently regulated for plant commodities.

HED has determined that translation of metabolism data from triadimefon
to triadimenol is not appropriate for the existing uses on cereal grains
and cotton. The metabolism studies with triadimefon were conducted using
a foliar application and triadimenol is used only as a seed treatment.
Additionally, in the submitted triadimenol seed treatment wheat study,
residues in grain were not identifiable due to the low activity found in
wheat grain. Therefore, HED concludes that the nature of the residue in
cereal grains and cotton is not adequately understood; however, based on
chemical structure and the probable metabolic pathway of triadimenol,
the residues of concern for tolerance expression and risk assessment are
likely to be triadimenol, KWG 1342, and KWG 1732 in/on cereal grains
(barley, corn, oats, rye, and wheat) and cotton. Separate metabolism
studies with triazole-^14^C and phenyl-^14^C labeled triadimenol applied
as a seed treatment to corn or wheat and cotton should be conducted to
confirm the residues of concern. The residues of concern for tolerance
expression and risk assessment for bananas are triadimenol and KWG 1342.

The Pesticide Analytical Manual (PAM) Vol. II does not contain a listing
for triadimenol (February 1997 Index). However, the methods listed for
triadimefon can be used for the determination of triadimenol, KWG 1323,
KWG 1342, and KWG 1732. PAM lists two gas chromatography with mass
spectrometry detection (GC/MS) methods (Methods I and II) for the
determination of triadimenol and its free and conjugated metabolites in
plant and livestock commodities. Both methods are common moiety methods.
The reported limit of quantitation (LOQ) is 0.05 and limit of detection
(LOD) is 0.01 ppm for both methods.

In conjunction with triadimefon reregistration, Bayer has proposed a
GC/MS method (Report No. 106549) for enforcement of tolerances for
residues of triadimefon, triadimenol, KWG 1342, KWG 1323, and KWG 1732
in/on barley, corn, cotton, oat, rye, and wheat commodities. The method
has been successfully radiovalidated and has undergone independent
laboratory validation. The reported method LOQ is 0.05 ppm for each
analyte in cereal grains and 0.02 ppm in each analyte in cotton.
Additionally, a GC method using a nitrogen phosphorus detector (NPD;
Report No. 80488) is available for determination of residues of
triadimenol, KWG 1342, and KWG 1323 and is adequate for the enforcement
of the banana tolerance. The method has undergone a successful Agency
method validation on tomatoes and was submitted to the FDA for
publication in PAM Vol. II. The reported method LOQ is 0.01 ppm for each
analyte.

[CONCLUSIONS AND RECOMMENDATIONS]{.underline}

[Processed Food/Feed]{.underline}

1\. [Field corn]{.underline}: The submitted data are adequate to fulfill
the requirement for a field corn grain processing study. As triadimenol
residues of concern were each below the LOQ (0.05 ppm) in/on corn grain
grown from seed treated at 5x the maximum application rate, a corn grain
processing study and tolerances for field corn processed commodities are
not required.

2\. [Cotton]{.underline}: The submitted data are adequate to fulfill the
requirement for a cottonseed processing study. As triadimenol residues
of concern were each below the LOQ (0.02 ppm) in/on cottonseed grown
from seed treated at 5x the maximum application rate, a cottonseed
processing study and tolerances for cotton processed commodities are not
required.

3\. [Wheat]{.underline}: The available wheat grain data do not fulfill
the requirement for a wheat grain processing study. Residues of
triadimenol and KWG 1342 were each \<LOQ (\<0.05 ppm) and residues of
KWG 1732 were 0.11 ppm and 0.23 ppm in/on two samples of wheat grain
grown from seed treated with triadimenol (FlC) at 5x the maximum rate.
However, the treated grain was not processed. Instead, the registrant
proposed translating data from a triadimefon wheat grain processing
study; however, these data cannot be translated to triadimenol due to
differences in the use patterns (seed treatment vs. late season foliar
sprays) that are likely to impact the potential for concentration of
residues in grain. The registrant should conduct a processing study
using the available wheat grain grown from the seeds treated with
triadimenol at 5x.

[DETAILED CONSIDERATIONS]{.underline}

[Residue Analytical Methods]{.underline}

Samples of field corn grain, cottonseed, and wheat grain were analyzed
for residues of triadimenol, KWG 1342, and KWG 1732 at ABC Laboratories
(Columbia, MO) using a GC/MS method (Bayer Corporation Report No.
106549). This method has been proposed for enforcement of tolerances for
triadimefon residues of concern and has undergone successful independent
laboratory validation (J. Punzi; D222403, D227497, and D227543;
7/13/2000).

Briefly, residues are extracted under reflux in methanol:water (7:3,
v:v) for 2 hours and then concentrated to an aqueous solution. The
extract is then hydrolyzed with cellulase at 37 C overnight (at pH 5.5)
and partitioned with dichloromethane:acetonitrile (3:2, v:v). The
aqueous phase, containing KWG 1732, is reserved. The organic phase is
dried using sodium sulfate and evaporated to dryness, and residues are
redissolved in ethyl acetate, cleaned up by gel permeation
chromatography, and separated by semi-preparative HPLC into two
fractions: one containing triadimenol and the other containing KWG 1342.
Triadimenol was determined directly by GC/MS; KWG 1342 was derivatized
prior to GC/MS analysis. The reported LOQ was 0.05 ppm for each analyte
in field corn and wheat grain and 0.02 ppm for each analyte in
cottonseed.

The reserved aqueous phase, containing KWG 1732, is acidified to pH 1
(using concentrated HCl) and the residues are partitioned into ethyl
acetate. The residues are then partitioned into 0.5 M sodium carbonate,
acidified to pH 1, and repartitioned back into ethyl acetate. The
residues are then evaporated to dryness, redissolved in
methanol:dichloromethane (20:80; v:v), methylated with trimethylsilyl
diazomethane, and cleaned up by silica gel solid phase extraction for
analysis by GC/MS. Triadimefon was used as an internal standard for KWG
1732 analysis. The reported LOQ was 0.05 ppm for field corn and wheat
grain and 0.02 ppm for cottonseed.

The registrant provided method validation and concurrent method recovery
data for the GC/MS method from fortifications at the LOQ. These recovery
data are presented in Table 1. These data indicate that the GC/MS method
is adequate for data collection purposes.

Table 1. Recoveries of triadimenol and its metabolites KWG 1342, and KWG
1732 from fortified samples of untreated field corn grain, cottonseed,
and wheat grain.

+--------+--------+---------+--------+---------+---------+---------+
| Com    | Triad  |         | KWG    |         | KWG     |         |
| modity | imenol |         | 1342   |         | 1732    |         |
+--------+--------+---------+--------+---------+---------+---------+
|        | F      | \%      | F      | \%      | Fortif  | \%      |
|        | ortifi | R       | ortifi | R       | ication | R       |
|        | cation | ecovery | cation | ecovery |         | ecovery |
|        |        | ^a^     |        | ^a^     | Level   | ^a^     |
|        | Level  |         | Level  |         | (ppm)   |         |
|        | (ppm)  |         | (ppm)  |         |         |         |
+--------+--------+---------+--------+---------+---------+---------+
| Field  | 0.05   | 76-84   | 0.05   | 86,88;  | 0.05    | 88-102  |
| corn   |        | (4)     |        | 134,    |         | (3)     |
|        |        |         |        |         |         |         |
| Grain  |        |         |        | 142     |         |         |
+--------+--------+---------+--------+---------+---------+---------+
| Cott   | 0.02   | 95-100  | 0.02   | 75-80   | 0.02    | 75-120  |
| onseed |        | (3)     |        | (3)     |         | (3)     |
+--------+--------+---------+--------+---------+---------+---------+
| Wheat  | 0.05   | 72-82   | 0.05   | 100-108 | 0.05    | 60, 62; |
| Grain  |        | (3)     |        | (3)     |         | 76      |
+--------+--------+---------+--------+---------+---------+---------+

^a^ Each value represents one sample unless otherwise indicated in
parentheses; recovery values outside the acceptable 70-120% range are
listed separately.

[Storage Stability Data]{.underline}

Samples of field corn grain, cottonseed, and wheat grain were placed in
frozen storage (temperature unspecified) within 4 hours of sample
collection, and then shipped frozen to the analytical laboratory, where
they were stored frozen (\~-20 C) until analysis. Subsamples of the
unginned cottonseed were removed from the freezer at the field trial
site after approximately 3 months of storage; these subsamples were
ginned, frozen, and then shipped to the analytical laboratory. Analyses
were completed 82-96 days following collection for field corn grain
samples, 201-236 days following collection for cottonseed samples, and
44-51 days following collection for wheat grain samples.

Storage stability data for triadimenol, KWG 1342, and KWG 1732 have been
submitted by Bayer Corporation to satisfy reregistration data
requirements for triadimefon. These data indicate that residues of
triadimenol and KWG 1342 are stable in wheat grain for up to 2 years of
at -20 C (S. Hummel; D168542 and D178884; 12/22/92) and residues of KWG
1732 are stable in wheat grain for up to 2.5 years at -20°C (J. Punzi;
D222403, D227497, and D227543; 7/13/2000). These data are adequate to
support the storage intervals and conditions of the samples from the
submitted field corn grain, cottonseed, and wheat grain studies.

[Magnitude of the Residue in Processed Food/Feed]{.underline}

[Field Corn]{.underline}

*Established tolerances*: No tolerance has been established for
triadimenol residues of concern in any field corn processed commodity. A
tolerance of 0.05 ppm has been established for triadimenol residues of
concern in/on field corn grain \[§180.450(a)\].

*Use directions:* The 2.65 lb/gal FlC formulation (EPA Reg. No. 7501-91)
is registered for use on field corn as a seed treatment at 0.062 lb ai
(1.0 oz ai) per 100 lb of seed. Application is to be made by mixing the
dosage in 16 fluid oz of water per 100 lb of seed. The use of treated
seed for feed, food or oil purposes is prohibited. A 45-day PHI has been
established for forage.

*Discussion of data:* Gustafson has submitted data (1998; MRID 44519801)
depicting the potential for concentration of triadimenol residues of
concern in field corn processed commodities. Field corn seed was treated
with the 2.65 lb/gal FlC formulation at 0.313 lb ai (5.0 oz ai) per 100
lb of seed (5x the maximum application rate) prior to planting. The
treated seed was planted in IA six days after treatment. One sample of
field corn grain grown from untreated seed and two samples of field corn
grain grown from treated seed were collected at maturity, 177 days after
planting. The field corn grain samples were placed in frozen storage
within 2 hours of collection, and then shipped frozen to the analytical
laboratory (ABC Laboratories), where they were stored frozen until
analysis.

Field corn grain samples were analyzed for residues of triadimenol, KWG
1342, and KWG 1732. Residues were below the LOQ (\<0.05 ppm) for each
analyte in/on one sample of untreated field corn grain and two samples
of treated field corn grain. Because no quantifiable residues were
observed in/on corn grain following treatment at 5x the maximum
application rate, a processing study was not conducted.

*Study summary:* The submitted data are adequate to fulfill the
requirements for a field corn grain processing study. As triadimenol
residues of concern were \<LOQ in/on corn grain grown from seed treated
at 5x the maximum application rate, a corn grain processing study and
tolerances for field corn processed commodities are not required.

[Cottonseed]{.underline}

*Established tolerances*: No tolerance has been established for
triadimenol residues of concern in any cottonseed processed commodity. A
tolerance of 0.02 ppm has been established for triadimenol residues of
concern in/on cottonseed \[§180.450(a)\].

*Use directions:* The 0.43 lb/gal EC formulation (EPA Reg. No. 7501-80)
is registered for use on cotton as a seed treatment at 0.040 lb ai (0.6
oz ai) per 100 lb of seed. The use of treated seed for feed, food or oil
purposes is prohibited.

The 2.65 lb/gal FlC formulation (EPA Reg. No. 7501-91) is registered for
use on cotton as a seed treatment at 0.062 lb ai (1.0 oz ai) per 100 lb
of seed. Application is to be made by mixing the dosage in 16 fluid oz
of water per 100 lb of seed. The use of treated seed for feed, food or
oil purposes is prohibited.

*Discussion of data:* Gustafson has submitted data (1998; MRID 44519802)
depicting the potential for concentration of triadimenol residues of
concern in cottonseed processed commodities. Cotton seed was treated
with the 2.65 lb/gal FlC formulation at 0.313 lb ai (5.0 oz ai) per 100
lb of seed (5x the maximum application rate) prior to planting. The
treated seed was planted in MS 13 days after treatment. One sample of
cottonseed grown from untreated seed and two samples of cottonseed grown
from treated seed were collected at maturity, 148 days after planting.
The samples were placed in frozen storage within 1 hour of collection.
Subsamples of the unginned cottonseed were removed from the freezer
after approximately 3 months of storage; these subsamples were ginned,
frozen, and then shipped to the analytical laboratory (ABC
Laboratories), where they were stored frozen until analysis.

Ginned cottonseed samples were analyzed for residues of triadimenol, KWG
1342, and KWG 1732. Residues were below the LOQ (\<0.02 ppm) for each
analyte in/on one sample of untreated cottonseed and two samples of
treated cottonseed. Because no quantifiable residues were observed
following treatment at 5x the maximum application rate, a processing
study was not conducted.

*Study summary:* The submitted data are adequate to fulfill the
requirement for a cottonseed processing study. As triadimenol residues
of concern were each below the LOQ (0.02 ppm) in cottonseed grown from
seed treated at 5x the maximum application rate, a cottonseed processing
study and tolerances for cotton processed commodities are not required.

[Wheat]{.underline}

*Established tolerances*: No tolerance has been established for
triadimenol residues of concern in any wheat processed commodity. A
tolerance of 0.05 ppm has been established for triadimenol residues of
concern in/on wheat grain \[§180.450(a)\].

*Use directions:* The 0.43 bl/gal EC formulation (EPA Reg. No. 7501-80),
2.65 lb/gal FlC formulation (EPA Reg. No. 7501-91), 2.6 lb/gal FlC
formulation (EPA Reg. No. 3125-424), and 6.25% D formulation (EPA Reg.
No. 7501-150) are registered for use on wheat as a seed treatment at
0.03 lb ai (0.5 oz ai) per 100 lb of seed. Application is to be made by
mixing the dosage in 16 fluid oz of water per 100 lb of seed (FlC
formulations only). The use of treated seed for feed, food or oil
purposes is prohibited. A 40-day PHI has been established for forage. We
note that the registrant has requested cancellation of the 6.25% D
formulation (65 FR 24477, 4/26/00).

*Discussion of data:* Gustafson has submitted data (1998; MRID 44519803)
depicting the potential for concentration of triadimenol residues of
concern in wheat processed commodities. Wheat seed was treated with the
2.65 lb/gal FlC formulation at 0.16 lb ai (2.5 oz ai) per 100 lb of seed
(5x the maximum application rate) prior to planting. The treated seed
was planted in TX 18 days after treatment. The registrant noted that the
treated seed did not grow as well as the untreated seed, and that the
treated plot suffered \~40-50% loss due to winter freezing conditions.
One sample of wheat grain grown from untreated seed and two samples of
wheat grain grown from treated seed were collected at maturity, 308 days
after planting. The wheat grain samples were placed in frozen storage
within 4 hours of collection, and then shipped frozen to the analytical
laboratory (ABC Laboratories), where they were stored frozen until
analysis.

Wheat grain samples were analyzed for residues of triadimenol, KWG 1342,
and KWG 1732. Residues were below the LOQ (\<0.05 ppm) for each analyte
in/on one sample of untreated wheat grain. Residues of triadimenol and
KWG 1342 were below the LOQ in/on two samples of treated wheat grain.
Detectable residues of KWG 1732 were observed in the wheat grain samples
at 0.11 ppm and 0.23 ppm.

The registrant did not process seed from the above 5x field trial;
instead, Gustafson cited a wheat processing study submitted by Bayer
Corporation to fulfill reregistration requirements for triadimefon
(1996; MRID 44029301). In that study, mature wheat grain was harvested
35 days following the last of two foliar broadcast applications of a 50%
WP triadimefon formulation (EPA Reg. No. 3125-340) at 0.9 lb
ai/A/application (ca. 4x the maximum seasonal use rate for triadimefon).
At the processing facility (Texas A&M University Food Protein and
Development Center, Bryan, TX), aspirated grain fractions were collected
(data for aspirated grain fractions are not presented here) and wheat
grain samples were processed into bran, wheat germ, flour, middlings,
and shorts, using a small-scale processing procedure which simulated
normal commercial processing conditions. The residues of triadimenol,
KWG 1342, and KWG 1732 found in wheat grain and its processed
commodities are presented in the Table 2. These data indicate that the
combined residues of triadimenol, KWG 1342, and KWG 1732 concentrate by
2.1x in wheat bran but do not concentrate in wheat flour, middlings,
shorts, or germ.

Table 2. Residues of triadimenol, KWG KWG 1342, and KWG 1732 in the
processed commodities of wheat grain harvested at maturity (35 days)
following the last of two foliar applications of triadimefon at 4x the
maximum seasonal triadimefon rate (MRID 44029301).

  ----------- ----------- ----------- ----------- ----------- -----------------
  Substrate                                                   

                                                              

  Grain                                                       

  Bran                                                        

  Flour                                                       

  Middlings                                                   

  Shorts                                                      

  Germ                                                        
  ----------- ----------- ----------- ----------- ----------- -----------------

^a^ Each residue value represents a single sample.

However, these data cannot be translated to triadimenol because of
differences in the use patterns of the two compounds. The use of
triadimefon on wheat, which Bayer is no longer supporting, involves late
season foliar applications that are more likely to result in surface
residues in/on wheat grain, as suggested by the concentration of
residues in bran in the above study. However, the use of triadimenol as
a seed treatment is unlikely to result in the concentration of residues
in the outer seed coat. To assess the potential for the concentration of
triadimenol residues in wheat grain, the registrant should conduct a
processing study using the available wheat grain grown from the 5x
treated seeds.

*Study summary:* The available wheat grain data do not fulfill the
requirement for a wheat grain processing study. Residues of triadimenol
and KWG 1342 were each \<LOQ (\<0.05 ppm) and residues of KWG 1732 were
0.11 ppm and 0.23 ppm in/on two samples of wheat grain grown from seed
treated with triadimenol (FlC) at 5x the maximum rate. However, the
treated grain was not processed. Instead, the registrant proposed
translating data from a triadimefon wheat grain processing study;
however, these data cannot be translated to triadimenol due to
differences in the use patterns (seed treatment vs. late season foliar
sprays) that are likely to impact the potential concentration of
residues. The registrant should conduct a processing study using the
available wheat grain grown from the seeds treated with triadimenol at
5x.

[AGENCY MEMORANDA CITED IN THIS REVIEW]{.underline}

DP Barcodes: D168542 and D178884

Subject: Triadimefon (109901): Storage Stability Data, PAM Multiresidue
Methods, Product Chemistry Data. CBRS Nos. 8566 and 9929.

From: S. Hummel

To M. Wilhite/B. Sidwell

Dated: 12/22/92

MRIDs: 41976601, 41976602, and 42307801-42307803

DP Barcodes: D222403, D227497, and D227543

Subject: Triadimefon. Independent Laboratory Validation, Radiovalidation
Data, and Storage Stability Data.

From: J. Punzi

To: B. Chambliss

Dated: 7/13/2000

MRIDs: 43870101, 44038901, 44041001, and 44041002

[MASTER RECORD IDENTIFICATION NUMBERS]{.underline}

The citations for the MRID documents referred to in this review are
presented below.

44029301 Grace, T. (1996) BAYLETON 50WP - Magnitude of the Residue in
Wheat Processed Products: Lab Project Number: BL19WH02: 107130: PR95322.
Unpublished study prepared by Bayer Corp.; Texas A&M University; and
Maxim Technologies, Inc. 2508 p.

44519801 Shen, S. (1998) Determination of Residues of Baytan 30 in
Processed Field Corn Fractions: Lab Project Number: 96-003: 963HI:
43514. Unpublished study prepared by ABC Labs., Inc. and Gustafson
Research and Development Center. 458 p.

44519802 Shen, S. (1998) Determination of Residues of Baytan 30 in
Processed Cotton Fractions: Lab Project Number: 96-001: 963HG: 43516.
Unpublished study prepared by ABC Labs., Inc. and Gustafson Research and
Development Center. 452 p.

44519803 Shen, S. (1998) Determination of Residues of Baytan 30 in
Processed Wheat Fractions: Lab Project Number: 96-002: 963HH: 43513.
Unpublished study prepared by ABC Labs., Inc. and Gustafson Research and
Development Center. 462 p.