Tetraconazole Residue Chemistry Summary Document D382300

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION

MEMORANDUM

Date: 14-April-2011

Subject: Tetraconazole. Residue Chemistry Summary for Application of Tetraconazole to Field 

Corn, Popcorn, Small Fruit Vine Climbing (Except Fuzzy Kiwifruit) Subgroup 13-07F, and 

Low-growing Berry Subgroup 13-07G (except cranberry). 

PC Code: 120603 DP Barcode: D382300

Decision No.: 435873 Registration Nos.: 80289-7 and 80289-8

Petition Nos.: 0E7735 (13-07F and 03-07G) and 0F7737

(field corn and popcorn)

Regulatory Action: Section 3

Risk Assessment Type: not applicable Case No.: 7043

TXR No.: not applicable CAS No.: 112281-77-3

MRID Nos.: 48131301, 48135102, 48135103, 48135104, 

48135105, and 48135106

40 CFR: 180.557

From: Tom Bloem, Chemist

Risk Assessment Branch 1, Health Effects Division (RAB1/HED); 7509P

Through: George F. Kramer, Ph.D., Senior Chemist

RAB1/HED (7509P)

To: Mary Waller/Lisa Jones (RM 21)

Barbara Madden (RM 05)

Registration Division (7505P) 

The subsequent text references the “free triazole metabolites” and the “non-free-triazole metabolites.” 

These terms refer to the following compounds: free triazole metabolites - 1,2,4-triazole (T; PC Code 

600074), triazolyl alanine (TA; PC Code 600011), triazolyl acetic acid (TAA; PC Code 600082), 

triazolyl hydroxypropionic acid (THP), and/or all labile conjugates of these compounds and non-freetriazole metabolites - tetraconazole metabolites of concern for risk assessment other than T, TA, TAA, 

THP and/or all labile conjugates of these compounds. 
Tetraconazole Residue Chemistry Summary Document D382300

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EXECUTIVE SUMMARY

Background: Tetraconazole (1-[2-(2,4-dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy)propyl]-1H-1,2,4-

triazole) is a systemic fungicide and is a member of the conazole/triazole class of pesticides. 

Tetraconazole acts by inhibiting the metabolic pathway leading to fungal sterol production (steroldemethylation inhibitor (DMI)) and is currently registered for application to sugar beets, grapes, peanuts, 

pecans, and soybeans with tolerances ranging from 0.03-1.0 ppm (40 CFR 180.557). Tolerances as a 

result of secondary residues are also established in/on hog, poultry, and ruminant commodities at 0.01-

0.25 ppm. 

The Interregional Research Project No. 4 (IR-4; Princeton, NJ) proposed a Section 3 Registration (PP# 

0E7735) for application of tetraconazole to the small fruit vine climbing (except fuzzy kiwifruit) 

subgroup 13-07F and low-growing berry subgroup 13-07G (except cranberry) and Isagro (Morrisville, 

NC) proposed a Section 3 Registration (PP# 0F7737) for application of tetraconazole to field corn and 

popcorn. In conjunction with these requests, the following tolerances for residues of tetraconazole per 

se were proposed (180.557(a)): small fruit vine climbing, except fuzzy kiwifruit subgroup 13-07F - 0.20 

ppm; low-growing berry subgroup 13-07G, except cranberry - 0.25 ppm; corn field, forage - 1.0 ppm; 

corn field, grain - 0.01 ppm; corn field, stover - 1.5 ppm; corn pop, grain - 0.01 ppm; and corn pop, 

stover - 1.5 ppm. IR-4 also requested the removal of the currently-established 0.20 ppm grape tolerance. 

IR-4 initially requested a Section 3 Registration for application to the low-growing berry subgroup 13-

07G. Since it was evident that residues in water from the cranberry use would alone result in dietary

exposures greater than HED’s level of concern, IR-4 submitted a letter and revised Section F 

withdrawing the request for a tolerance on cranberry as part of the 13-07G subgroup. A revised Section 

B was not submitted.

Directions for Use: IR-4 proposed application of Mettle 125ME Fungicide (microemulsion 

formulation; 1 lb ai/gallon; EPA Reg. No. 80289-8) to the small fruit vine climbing (except fuzzy

kiwifruit) subgroup 13-07F and the low-growing berry subgroup 13-07G for control of powdery mildew, 

black rot, anthracnose, leaf spot, leaf blight, and/or Oidium spp. Isagrow proposed application of 

Domark®230ME Fungicide (1.9 lb ai/gallon; EPA Reg. No. 80289-7) to popcorn and field corn 

(including field corn grown for seed) for control of ray leaf spot, rust (common and southern),

anthracnose leaf blight, eye spot, northern/southern corn leaf blight, northern corn leaf spot, physoderma 

brown spot, and yellow leaf blight. Table 3 is a summary of the proposed application scenarios. 

As indicated above, a revised Section B with the cranberry instructions removed is requested. In

addition, since the grape and strawberry field trial data did not include an adjuvant with the spray

solution, HED requests that the revised Section B also prohibit the additional of adjuvant to the spray

solutions for application to crops in subgroups 13-07F and 13-07G. 

Nature of the Residue - Plants: The HED Metabolism Assessment Review Committee (MARC)

reviewed the sugar beet (triazole ring labeled study), grape (triazole and phenyl ring labeled studies), and 

wheat (triazole and phenyl ring labeled studies) metabolism studies (D264157, W. Donovan, 19-Apr2000). The MARC tentatively concluded that the residue of concern in banana, peanut, and sugar beet 

was tetraconazole per se. This decision was not finalized due to uncertainty concerning the toxicity of 

the free triazole metabolites, incomplete identification of residues in wheat straw, and the lack of a 

phenyl-labeled sugar beet metabolism study. HED has subsequently determined that the free triazole 

metabolites are of toxicological concern (TXR No. 0052011) and received/reviewed the requested 
Tetraconazole Residue Chemistry Summary Document D382300

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metabolism studies. Since the MARC was disbanded prior to the submission/review of the requested 

data and prior to the submission of the triazole-labeled soybean metabolism study, a final conclusion 

pertaining to the residues of concern in plants was not made by the MARC. 

Based on the tentative conclusions made by the MARC, the results of the metabolism studies, and 

toxicological considerations, HED concludes that the residue of concern for tolerance enforcement in all 

crops is tetraconazole per se and the residues of concern for risk assessment are as follows: (1) shelled 

pea and bean (succulent and dried): tetraconazole and T, TA, TAA, and all labile conjugates of these 

compounds and (2) all remaining crops: tetraconazole, M14360-alcohol (free and conjugated), M14360-

acid, M14360-DFA, M14360-hydroxydetriazolyl-O-malonyldiglucoside, and T, TA, TAA and all labile 

conjugates of these compounds. HED notes that Syngenta developed a common moiety method for 

propiconazole which employs base hydrolysis followed by oxidation and that a similar method would be 

appropriate for determination of the tetraconazole non-free-triazole metabolites (non-free-triazole 

metabolites hydrolyzed/oxidized to 2,4-dichlorobenzoic acid). For a full discussion pertaining to the 

residues of concern in plants see the HED risk assessment document D321751 (M. Clock-Rust et al., 26-

Jan-2007).

Nature of the Residue - Livestock: The MARC reviewed the goat metabolism studies and tentatively

determined that the residues of concern in livestock were tetraconazole and T (D264157, W. Donovan, 

19-Apr-2000). This decision was not finalized due to uncertainty concerning the toxicity of T and due to 

the lack of a poultry metabolism study. HED has subsequently determined that the free triazole 

metabolites are of toxicological concern (TXR No. 0052011) and received/reviewed a poultry

metabolism study (D282558, W. Donovan, 17-May-2002). Since the MARC was disbanded prior to the 

submission and/or review of these data, a final conclusion pertaining to the residues of concern in 

livestock was not made by the MARC. 

Based on the tentative conclusions made by the MARC, the results of the metabolism studies, and 

toxicological considerations, HED concludes that the residue of concern in livestock for tolerance 

enforcement is tetraconazole per se and the residues of concern for risk assessment are tetraconazole, 

M14360-alcohol (free and conjugated), M14360-acid, M14360-DFA, M14360(C-1)-alcohol (free and 

conjugated), M14360-hydroxydetriazolyl-O-malonyldiglucoside, and T, TA, THP, and TAA and all 

labile conjugates of these compounds. HED included as residues of concern the free triazole metabolites 

(excluding T) and non-free-triazole metabolites as these were identified as significant residues in plants; 

T was included as it was a significant metabolite in the livestock and plant metabolism studies. For a 

full discussion pertaining to the residues of concern in livestock see the HED risk assessment document 

D321751 (M. Clock-Rust et al., 26-Jan-2007).

Magnitude of the Residue - Proposed Primary Crops: Adequate grape (representative crop for 13-07F 

subgroup), strawberry (representative crop for 13-07G subgroup), and field corn magnitude of the 

residue data were submitted. The field trials were geographically distributed as suggested in Table 5 of 

860.1500, were conducted with the proposed formulation, and employed the proposed application 

scenario. Adequate grape and field corn processing studies were also submitted and these studies 

indicate that separate tolerances in/on the grape and field corn processed commodities are unnecessary. 

Provided a revised Section B is submitted which eliminates the cranberry application instructions and 

prohibits the addition of adjuvants to the spray solutions for 13-07F and 13-07G crops, HED concludes 

that the following tolerances for residues of tetraconazole per se are appropriate (the currently

established grape tolerance should be deleted; revised Section F is requested): small fruit vine climbing 

(except fuzzy kiwifruit) subgroup 13-07F - 0.20 ppm; low-growing berry subgroup 13-07G (except 
Tetraconazole Residue Chemistry Summary Document D382300

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cranberry) - 0.25 ppm; is appropriate; ): corn, field, grain - 0.01 ppm; corn, field, forage - 1.1 ppm; corn, 

field, stover - 1.7 ppm; corn, pop - 0.01 ppm; and corn, pop, stover - 1.7 ppm. The following storage 

stability data are needed to validate the magnitude of the residue data: T, TA, and TAA in strawberry

(516 days); tetraconazole in corn grain, forage, and stover (266 days; grain data will be translated to all 

processed commodities excluding refined oil); T in corn forage and stover (263 days); and tetraconazole, 

T, TA, and TAA in refined corn oil (198 days).

Magnitude of the Residue - Livestock: Tolerances for residues of tetraconazole per se are currently

established in/on ruminant (cattle, goat, horse, and sheep) fat (0.02 ppm), liver (0.20 ppm), meat (0.01 

ppm), and meat byproducts (except liver; 0.01 ppm) and milk (0.01 ppm) and milk fat (0.25 ppm). 

Tolerances are also established in/on hog fat (0.01 ppm), hog liver (0.05 ppm), and hog meat (0.01 ppm) 

and in/on poultry fat (0.05 ppm), meat (0.01 ppm), meat byproducts (0.01 ppm), and egg (0.02 ppm). 

Based on the residues in/on the proposed/registered crops, the livestock maximum reasonably balanced 

dietary burdens (MRBDBs) are as follows: beef cattle - 0.519 ppm, dairy cattle - 1.292 ppm, hog - 0.035 

ppm, and poultry - 0.050 ppm. Based on the MRBDBs and the previously submitted and reviewed dairy

cattle (D254411, W. Donovan, 18-May-2000) and poultry (46614307.der.doc; D329379, T. Bloem, 23-

Jan-2007) feeding studies, HED concludes that the following tolerances are appropriate (the currently

established hog, egg, poultry meat and fat, and ruminant meat tolerances remain appropriate; a revised 

Section F is requested): milk - 0.03 ppm; milk, fat - 0.75 ppm; fat (cattle, goat, horse, and sheep) - 0.15 

ppm; liver (cattle, goat, horse, and sheep) - 1.5 ppm; meat byproducts (except liver; cattle, goat, hog, 

horse, and sheep) - 0.15 ppm; and poultry, meat byproducts - 0.05 ppm (currently established hog, 

ruminant meat, and poultry meat and fat tolerances remain appropriate). 

Nature/Magnitude of the Residue - Rotational Crops: Based on the results of the confined rotational 

crop studies and toxicological considerations, HED concluded that the residue of concern in rotational 

crops for tolerance enforcement is tetraconazole per se and the residues of concern for risk assessment 

are tetraconazole, M14360-acid, M14360-DFA, M14360(C-1)-alcohol (free and conjugated), and TA, 

THP, and TAA and all labile conjugates of these compounds (for a full discussion see D331476, M. 

Clock-Rust et al., 26-Jan-2007). The petitioner previously submitted data concerning the magnitude of 

tetraconazole per se residues in rotational crops and these data, as well as HED’s conclusions concerning 

the magnitude of tetraconazole per se residues in rotational crops following treatment at the proposed 

rates, are summarized below. 

The field rotational crop studies resulted in tetraconazole per se residues of <0.02 ppm in all studied 

rotational crops (wheat grain, pea, potato, canola seed, sugar beet (top and root)), excluding wheat straw, 

planted 7-9 days after a bare soil application at 1.4-17x the proposed seasonal rates (D278236, W. 

Donovan, 22-Oct-2001). Residues of tetraconazole per se were <0.02-0.05 ppm in wheat straw when 

planted in fields treated at 4.2-17x. Based on these data, the proposed plant-back intervals, and proposed 

application rates, HED concludes that residues of tetraconazole per se in rotational crops planted in 

fields treated at the proposed rate will be insignificant. 

Analytical Methods: Adequate analytical methods are available to enforce the currently established 

tetraconazole per se plant and livestock tolerances (D280006, W. Donovan, 10-Jan-2002, D267481, 12-

Oct-2000; D278236, W. Donovan, 22-Oct-2001). As part of the corn petition, Isagro submitted 

adequate method validation and independent laboratory validation (ILV) data which indicates that the 

QuEChERS multi-residue method L 00.00-115 (48135104.der.docx) is capable of quantifying 

tetraconazole residues in/on a variety of fruit, cereal grain, root, oilseed, and livestock commodities (note

that mean recoveries in/on wheat straw were 50-70%;). Based on these data and since the extraction 
Tetraconazole Residue Chemistry Summary Document D382300

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solvent employed in the QuEChERS method (acetonitrile) is similar to the extraction solvent employed 

in the radiovalidated enforcement methods (acetone), HED concludes that the QuEChERS method is 

adequate for enforcement of the tolerances recommended in the current document and forwarded the 

method to the Food and Drug Administration (FDA; D386650, T. Bloem, 14-Apr-2011)

Multiresidue Methods (MRMs) Testing: HED has previously reviewed information concerning the 

MRMs testing of tetraconazole and forwarded these data to the FDA (D278236, W. Donovan, 22-Oct2001; D332231, T. Bloem, 13-Sep-2006). Tetraconazole was not recovered through the MRM 

Protocols. 

Recommendation: IR-4 proposed a Section 3 Registration (PP# 0E7735) for application of 

tetraconazole to the small fruit vine climbing (except fuzzy kiwifruit) subgroup 13-07F and low-growing

berry subgroup 13-07G (except cranberry) and Isagro proposed a Section 3 Registration (PP# 0F7737) 

for application of tetraconazole to field corn and popcorn. The following are HED recommendations for 

each of these petitions. A human-health risk assessment will be prepared as a separate document.

PP# 0E7735 (subgroups 13-07F and 13-07G (except cranberry)): Provided revised Sections B and F are

submitted, HED concludes that the residue chemistry database supports a conditional registration for 

application of the proposed tetraconazole formulation to the small fruit vine climbing (except fuzzy

kiwifruit) subgroup 13-07F and low-growing berry subgroup 13-07G (except cranberry). HED 

recommends that the following permanent tolerances for residues of tetraconazole per se be established 

as a result of this registration (currently established grape tolerance should be removed): small fruit vine 

climbing (except fuzzy kiwifruit) subgroup 13-07F - 0.20 ppm and low-growing berry subgroup 13-07G 

(except cranberry) - 0.25 ppm. The residue chemistry database may support an unconditional 

registration upon submission of storage stability data demonstrating the stability of T, TA, and TAA 

residues in/on strawberry (516 days). 

PP# 0F7737 (field corn and popcorn): Provided a revised Section F is submitted, HED concludes that 

the residue chemistry database supports a conditional registration for application of the proposed 

tetraconazole formulation to field corn and popcorn. HED recommends that the following permanent 

tolerances for residues of tetraconazole per se be established as a result of this registration: corn, field, 

grain - 0.01 ppm; corn, field, forage - 1.1 ppm; corn, field, stover - 1.7 ppm; corn, pop - 0.01 ppm; corn, 

pop, stover - 1.7 ppm; milk - 0.03 ppm; milk, fat - 0.75 ppm; fat (cattle, goat, horse, and sheep) - 0.15 

ppm; liver (cattle, goat, horse, and sheep) - 1.5 ppm; meat byproducts (except liver; cattle, goat, hog, 

horse, and sheep) - 0.15 ppm; poultry, meat byproducts - 0.05 ppm. The residue chemistry database may

support an unconditional registration upon submission of the following storage stability data: 

tetraconazole in corn grain, forage, and stover (266 days); T in corn forage and stover (263 days); and 

tetraconazole, T, TA, and TAA in refined corn oil (198 days). HED notes that MRID 47606601, which 

presents information concerning the stability of T, TA, and TAA in several matrices, has been submitted 

to the Agency but has not yet been reviewed. Provided these data demonstrate the stability of T, TA, and

TAA in the above matrices, no additional information will be required for these analytes. 

HED also recommends that the tetraconazole tolerance expression be changed to the following (40 CFR 

180.557(a)): 

180.557(a): Tolerances are established for residues of tetraconazole, including its metabolites and degradates, 

in or on the commodities listed below. Compliance with the following tolerance levels is to be determined by

measuring only tetraconazole (1-[2-(2,4-dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy)propyl]-1H-1,2,4-

triazole).
Tetraconazole Residue Chemistry Summary Document D382300

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DETAILED CONSIDERATIONS

Background

Tetraconazole is a systemic fungicide and is a member of the conazole/triazole class of pesticides. 

Tetraconazole acts by inhibiting the metabolic pathway leading to fungal sterol production (sterol DMI). 

Table 1: Test Compound Nomenclature.

Chemical Structure

N

N

N

OCF2CF2H

Cl

Cl

Common name Tetraconazole

Company experimental name None Specified in Submission

IUPAC name (±)-2-(2,4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-yl)propyl-1,1,2,2-tetrafluoroethyl ether

CAS name 1-[2-(2,4-dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy) propyl]-1H-1,2,4-triazole

CAS # 112281-77-3

Table 2: Physicochemical Properties of the Technical Grade Tetraconazole.

Melting point/range Not applicable - test is a viscous liquid 

MRID 44268104; D259842, 

B. Kitchens, 11-Apr-2000.

pH 5.48 in DI H2O; 5.47 for saturated 

solution at 20°C

Density 1.4382 g/ml at 20°C

1.4252 g/ml at 30°C 

Water solubility (PAI >94.16%) 159.31 mg/L at 25°C

Solvent solubility not available

Vapor pressure (PAI >99.65%) 0.13 x 102

Pa at 35.5°C; 0.58 x 102Pa 

at 46.5°C; 2.985 x 102Pa at 60°C

MRID 44305301; D259842, 

B. Kitchens, 11-Apr-2000.

Dissociation constant (Ka) 0.158 - 0.316 MRID 46055603; D294198, 

B. Kitchens, 26-Jan-2004.

Octanol/water partition coefficient (PAI >99.65%) log Pow = 3.53 at 25°C MRID 44305301; D259842, 

B. Kitchens, 11-Apr-2000.

UV/visible absorption spectrum not available

OPPTS GLN 860.1200 Directions for Use

IR-4 proposed application of Mettle 125ME Fungicide (ME; 1 lb ai/gallon; EPA Reg. No. 80289-8) 

to the small fruit vine climbing (except fuzzy kiwifruit) subgroup 13-07F and the low-growing berry

subgroup 13-07G for control of powdery mildew, black rot, anthracnose, leaf spot, leaf blight, and/or 

Oidium spp. Isagrow proposed application of Domark®230ME Fungicide (ME; 1.9 lb ai/gallon; EPA 

Reg. No. 80289-7) to popcorn and field corn (including field corn grown for seed) for control of ray

leaf spot, rust (common and southern), anthracnose leaf blight, eye spot, northern/southern corn leaf 

blight, northern corn leaf spot, physoderma brown spot, and yellow leaf blight. Table 3 is a summary

of the proposed application scenarios. 

IR-4 initially requested a Section 3 Registration for application to the low-growing berry subgroup 13-

07G. Since it was evident that residues in water from the cranberry use would alone result in dietary

exposures greater than HED’s level of concern, IR-4 submitted a letter and revised Section F 

withdrawing the request for a tolerance on cranberry as part of the 13-07G subgroup. A revised 

Section B was not submitted. Therefore, HED requests a revised section B with the cranberry

application instructions removed. In addition, since the grape and strawberry field trial data did not 

include an adjuvant with the spray solution, HED requests that the revised Section B also prohibit the 

additional of an adjuvant to the 13-07F and 13-07G spray solutions.
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Table 3: Proposed Application Scenarios.

Formulation Single Rate

(lb ai/acre)

Seasonal Rate

(lb ai/acre)

No. 

Apps

RTI1

(days)

PHI1

(days) Comments

small fruit vine climbing (except fuzzy kiwifruit) subgroup 13-07F (grape, gooseberry, Amur river grape, 

hardy kiwifruit, maypop, schisandra berry, and cultivars, varieties, and/or hybrids of these)

Mettle 125 ME

Fungicide (EPA Reg. 

No. 80289-8; 1 lb 

ai/gallon

0.023-0.039 0.08 2 14 14

-Ground (sufficient volume for through coverage), aerial (≥10 GPA), 

and chemigation applications are permitted.

-Do not apply more than 0.08 lb ai/acre/season.

-The label indicates the following rotational crop restrictions: 

registered/proposed crops may be planted 0 days after the last 

application; all other crops may be planted 15 days after the last 

application. 

low-growing berry subgroup 13-07G (strawberry, lowbush blueberry, bearberry, bilberry, cloudberry, 

cranberry, lingonberry, muntries, partridgeberry, and cultivars, varieties, and/or hybrids of these)

Mettle 125 ME

Fungicide (EPA Reg. 

No. 80289-8; 1 lb 

ai/gallon

0.023-0.039 0.16 4 14 0

-Ground (sufficient volume for through coverage), aerial (≥10 GPA), 

and chemigation applications are permitted.

-Do not apply more than 0.16 lb ai/acre/season.

-The label indicates the following rotational crop restrictions:

registered/proposed crops may be planted 0 days after the last 

application; all other crops may be planted 15 days after the last 

application. 

popcorn and field corn (including field corn grown for seed)

Domark®230ME 

Fungicide (EPA Reg. 

No. 80289-7; 1.9 lb 

ai/gallon)

0.045-0.090 0.09 2 7

not 

specifi

ed

-Do not apply after corn growth stage R3 (brown silk/milk).

- Ground (sufficient volume for through coverage), aerial (≥2 GPA), 

and chemigation applications are permitted.

-The label indicates the following rotational crop restrictions:

registered/proposed crops may be planted 0 days after the last 

application; sugarcane and small grains (barley, buckwheat, millet, 

oats, rice, rye, triticale, and wheat) - 45 days after the last application; 

and all other crops - 120 days after the last application. 

1

 PHI = preharvest interval; RTI = retreatment interval.

OPPTS GLN 860.1300 Nature of the Residue –Plants/Livestock

See Executive Summary. 

OPPTS GLN 860.1340 Residue Analytical Method

48135102.der1.docx (field corn field trial); 48135102.der2.docx (field corn processing); 48131301.der.docx (strawberry); 

48135104.der.docx (QuEChERS method)

Enforcement Method: Adequate analytical methods are available to enforce the currently established 

tetraconazole per se plant and livestock tolerances (D280006, W. Donovan, 10-Jan-2002, D267481, 

12-Oct-2000; D278236, W. Donovan, 22-Oct-2001). As part of the corn petition, Isagro submitted 

adequate method validation and ILV data which indicates that the QuEChERS multi-residue method L

00.00-115 (48135104.der.docx) is capable of quantifying tetraconazole residues in/on a variety of fruit, 

cereal grain, root, oilseed, and livestock commodities (note that mean recoveries in/on wheat straw 

were 50-70%;). Since the extraction solvent employed in the QuEChERS method (acetonitrile) is 

similar to the extraction solvent employed in the radiovalidated enforcement methods (acetone), HED 

concludes that the radiovalidation of the QuEChERS method is unnecessary. HED concludes that the 

QuEChERS method is adequate for enforcement of the tolerances recommended in the current 

document. Since the ILV study indicated that slight modifications to the QuEChERS method was 

necessary for quantification of tetraconazole, the ILV study was forwarded to the FDA (D386650, T. 

Bloem, 14-Apr-2011). 
Tetraconazole Residue Chemistry Summary Document D382300

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Analytical Methods Employed in the Field Trial and Processing Studies: The grape, strawberry, and 

field corn samples from the magnitude of the residues studies were analyzed for residues of 

tetraconazole, T, TA, and TAA using adequately validated methods (see below for summaries of these 

methods). Based on the LLMV, the LOQ was 0.05 ppm for tetraconazole in/on strawberry, 0.01 ppm 

for T, TA, and TAA in/on strawberry, and 0.01 ppm for tetraconazole, T, TA, and TAA in/on all field 

corn and grape matrices. The method employed for determination of tetraconazole per se in 

strawberry, grape, and field corn commodities used the same or a sufficiently similar solvent as the 

current radiovalidated enforcement method (D280006, W. Donovan, 10-Jan-2002). The method used 

for determination of T, TA, and TAA is identical to method previously determined to be acceptable 

(D329379, T. Bloem, 23-Jan-2007). HED concludes that these methods are appropriate for datacollection purposes. 

Tetraconazole - Strawberry: The homogenized samples were extracted with acetone and filtered. 

After rinsing the flask and filter cake with acetone, the acetone in the filtrate was rotary evaporated to 

obtain an aqueous extract. The aqueous extract was partitioned with dichloromethane/saturated 

sodium chloride. The organic phase was filtered through a drying agent and cleaned up using an

activated carbon/silica gel column. The column eluant was rotary evaporated to dryness and the 

residues were dissolved in ethyl acetate. Analysis of the extracts was performed using a gas 

chromatograph/nitrogen-phosphors detector (GC/NPD). 

Tetraconazole – Grape RAC and Processed Commodities: The grape and grape juice samples were 

extracted by homogenizing with acetone and the raisin samples were extracted by homogenizing with 

acetone:water (7:3). The samples were centrifuged, concentrated to dryness, reconstituted in 

methanol:water:formic acid (65:35:0.1), and analyzed via liquid chromatography/mass 

spectrometer/mass spectrometer (LC/MS/MS). 

Tetraconazole - QuEChERS Method used for Field Corn RAC and Processed Commodities Excluding 

Corn Oil: The homogenized samples were shaken and centrifuged with acetonitrile containing 

anhydrous magnesium sulfate, sodium chloride, sodium citrate tribasic dehydrate, and sodium citrate 

dibasic sesquihydrate. The extracts were purified through a column containing anhydrous magnesium 

sulfate, primary secondary amines (PSA), and carbon and analyzed for tetraconazole using LC/MS.

Tetraconazole - Modified QuEChERS Method used for Field Corn Oil - Tetraconazole: Corn oil 

samples were extracted with acetonitrile saturated with n-hexane and then purified through a column 

containing anhydrous magnesium sulfate, PSA, carbon, and C18 and analyzed for tetraconazole using 

LC/MS.

T, TA, and TAA - Field Corn (all RACs) and Strawberry (Pyxant Method 1572.02): The homogenized

samples were extracted with methanol/water (80:20, v/v) followed by derivatization with 3N HCl in nbutanol solution and subsequent derivatization with heptafluorobutyric anhydride for TA and TAA and

dansyl chloride for T. The derivatized extracts were analyzed for metabolites T, TA, and TAA using 

LC/MS/MS.

OPPTS 860.1360 – MRM

HED has previously reviewed information concerning the MRMs testing of tetraconazole and 

forwarded these data to FDA (D278236, W. Donovan, 22-Oct-2001; D332231, T. Bloem, 13-Sep2006). Tetraconazole was not recovered through the MRM Protocols. 
Tetraconazole Residue Chemistry Summary Document D382300

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OPPTS GLN 860.1380 - Storage Stability Data

48135102.der1.docx (field corn field trial); 48135102.der2.docx (field corn processing); 48131301.der.docx (strawberry); 

47270101.der.doc (grape)

Samples from the field trial and processing studies submitted in support of the current petition were 

frozen upon collection and remained frozen until analysis. Table 4 is a summary of the storage 

intervals from collection to analysis and the available data validating these intervals. The following 

storage stability data are needed to validate the relevant residue data: T, TA, and TAA in strawberry

(516 days); tetraconazole in corn grain, forage, and stover (266 days; grain data will be translated to all 

processed commodities excluding refined oil); T in corn forage and stover (263 days); and 

tetraconazole, T, TA, and TAA in refined corn oil (198 days). HED notes that MRID 47606601, 

which presents information concerning the stability of T, TA, and TAA in several matrices, has been 

submitted to the Agency but has not yet been reviewed. Provided these data demonstrate the stability

of T, TA, and TAA in the above matrices, no additional information will be required for these 

analytes. 

Table 4: Summary of Storage Conditions/Intervals and Available Data validating these Conditions Intervals. 

Matrix Analyte Storage 

Temp.

Actual Storage 

Duration Interval of Demonstrated Storage Stability

strawberry

tetraconazole

frozen

≤203 days 245 days in/on strawberry; 48131301.der.docx.

T, TA, TAA ≤516 days Not provided.

grape

tetraconazole

frozen

≤236 days 245 days in/on strawberry; 48131301.der.docx.

T, TA, TAA ≤236 days 12 months in apple (46568301.der).

grape juice and raisin

tetraconazole

frozen 64 days (juice)

91 days (raisin)

69 days in grape juice and 91 days in raisin; 47435201.der.doc.

T, TA, TAA 12 months in apple (46568301.der) and 130 days in apple juice 

(47090446.der). 

corn forage

tetraconazole -20°C

≤266 days

Not provided; note that grain storage stability data will be translated 

to all processed commodities excluding refined oil. 

corn grain and grain 

processed commodities

(excluding corn oil)

≤235 days

corn stover ≤229 days

corn grain and grain 

processed commodities

(excluding corn oil)

T, TA, TAA -20°C ≤263 days

T - 12 months in/on wheat grain (D361110, D. Soderberg, 26-Feb2010).

TA and TAA - 26 months on wheat grain (D361110, D. Soderberg, 

26-Feb-2010); 13 months in/on wheat forage and hay; and 13 months 

in/on corn cob, forage, and straw (D338246, M. Doherty, 28-May2008; declined ~3% per month in/on wheat straw).

The wheat grain storage stability data was translated to all corn grain 

commodities excluding refined corn oil.

corn forage and stover

T -20°C ≤263 days Not provided.

TA and TAA -20°C ≤263 days

TA and TAA - 26 months on wheat grain (D361110, D. Soderberg, 

26-Feb-2010); 13 months in/on wheat forage and hay; and 13 months 

in/on corn cob, forage, and straw (D338246, M. Doherty, 28-May2008; declined ~3% per month in/on wheat straw).

refined corn oil

tetraconazole, 

T, TA, and 

TAA

-20°C ≤198 days Not provided.
Tetraconazole Residue Chemistry Summary Document D382300

page 10 of 24

OPPTS 860.1480 - Meat/Milk/Poultry/Eggs

Tolerances for residues of tetraconazole per se are currently established in/on ruminant (cattle, goat, 

horse, and sheep) fat (0.02 ppm), liver (0.20 ppm), meat (0.01 ppm), and meat byproducts (except 

liver; 0.01 ppm) and milk (0.01 ppm) and milk fat (0.25 ppm). Tolerances are also established in/on 

hog fat (0.01 ppm), hog liver (0.05 ppm), and hog meat (0.01 ppm) and in/on poultry fat (0.05 ppm), 

meat (0.01 ppm), meat byproducts (0.01 ppm), and egg (0.02 ppm). 

Table 5 is a summary of the tetraconazole per se MRBDBs calculations for beef cattle (0.519 ppm), 

dairy cattle (1.292 ppm), hog (0.035 ppm), and poultry (0.050 ppm). The dietary burdens were 

calculated using the guidance developed as part of the OPPTS 860.1000 Table 1 Feedstuff Revisions 

(J. Stokes, HED; June-2008). Note that the labels prohibit feeding peanut hay and soybean forage/hay

to livestock. The following text is a summary of the magnitude of tetraconazole per se residues in 

livestock; information concerning the magnitude of the remaining residues of concern can be found in 

the dietary exposure (D381912, T. Bloem, 14-Apr-2011) and/or risk assessment (D380618, A. 

Nowotarski et al., in draft) documents.

Ruminants: A cattle feeding/depuration study depicting residues of tetraconazole per se incurred in 

dairy cattle milk and tissues following dosing with tetraconazole was previously submitted and 

reviewed (D254411, W. Donovan, 18-May-2000). Dairy cows were orally dosed for 28-30 days with 

tetraconazole at 0.34 ppm, 1.02 ppm, and 3.4 ppm. These doses are 0.3x, 0.8x, and 2.6x the dairy

cattle MRBDB. Cows were milked twice daily (a.m. and p.m.) and the morning and evening milk 

collections were composited daily for each cow. Subsamples of milk collected on Days 14 and 28 

were separated into cream and skim milk. Cattle were sacrificed within 24 hours of the final dose and 

samples of liver, kidney, fat (pooled perirenal and omental), subcutaneous fat, and skeletal muscle

(pooled pectoralis and adductor muscle of the thigh) were collected after sacrifice. The samples were 

analyzed for residues of tetraconazole per se using an adequately validated method (storage interval 

has also been validated). Residues in milk reached a plateau by the third day of dosing. Table 6 is a 

summary of the maximum tetraconazole per se residues in each of the ruminant matrices from the 

feeding study and the estimated residue based on the dairy cattle MRBDB. The dairy cattle MRBDB 

was used for estimation of residues in all ruminant commodities (milk and tissues) as it is higher than 

that for beef cattle.

Based on the submitted ruminant feeding study and the MRBDB for dairy cattle, HED concludes that 

the following tolerances for residues of tetraconazole per se in ruminants and milk are appropriate (the 

currently established ruminant meat tolerances remain appropriate; a revised Section F is requested): 

milk - 0.03 ppm; milk, fat - 0.75 ppm; fat (cattle, goat, horse, and sheep) - 0.15 ppm; liver (cattle, goat, 

horse, and sheep) - 1.5 ppm; meat byproducts (except liver; cattle, goat, hog, horse, and sheep) - 0.15

ppm. Due to the high residue in liver as compared to the other tissue residues, HED concluded that a 

separate tolerance on liver and meat byproducts was appropriate. 

Hog: Based on the hog MRBDB and the cattle feeding study, HED concludes that the currently

established hog tolerances remain appropriate. 

Poultry: A poultry feeding/depuration study depicting residues of tetraconazole per se incurred in 

eggs and poultry tissues following dosing with tetraconazole was previously submitted and reviewed 

(46614307.der.doc; D329379, T. Bloem, 23-Jan-2007). Hens were orally dosed for 40 days with 

tetraconazole at 0.069 ppm, 0.241 ppm, and 0.714 ppm. These doses are equivalent to 1.4x, 4.8x, and 
Tetraconazole Residue Chemistry Summary Document D382300

page 11 of 24

14x the poultry MRBDB. Eggs were collected twice daily throughout the feeding study. Hens were 

sacrificed within 16-24 hours of the final dose and samples of liver, kidney, skeletal muscle, 

abdominal fat, and skin/subcutaneous fat were collected. The samples were analyzed for residues of 

tetraconazole per se using an adequately validated method (storage interval has also been validated). 

Tetraconazole residues in egg reached a plateau by the tenth day of dosing. Table 6 is a summary of 

the maximum tetraconazole residues in each of the poultry matrices from the feeding study and the 

estimated residue based on the poultry MRBDB. 

HED concludes that the currently established egg, poultry fat, and poultry meat tolerances remain 

appropriate. Since the meat byproduct tolerances is based on the highest residue in tissue (muscle, fat, 

liver, and kidney), HED concludes that the poultry meat byproduct tolerance should be increased to 

0.05 ppm. A revised Section F is requested.

Table 5: Livestock MRBDB Calculations.

Commodity1 % diet2 % dry matter HED-recommended 

tolerance (ppm) dietary burden3

beef cattle

field corn forage (R) 15 40 1.1 0.412

aspirated grain fractions (CC) 5 85 1.0 0.059

sugar beet molasses (CC) 10 75 0.25 0.033

field corn grain (CC) 65 88 0.01 0.007

soybean seed (PC) 5 89 0.15 0.008

total 100 -- -- 0.519

dairy cattle

field corn forage (R) 45 40 1.1 1.238

sugar beet molasses (CC) 10 75 0.25 0.033

field corn grain (CC) 35 88 0.01 0.004

soybean seed (PC) 10 89 0.15 0.017

total 100 -- -- 1.292

Poultry

field corn grain (CC) 75 -- 0.01 0.009

soybean meal (PC) 25 -- 0.15 0.041

total 100 -- -- 0.050

Hog

field corn grain (CC) 85 -- 0.01 0.010

soybean seed (PC) 15 -- 0.15 0.025

total 100 -- -- 0.035

1

 R = roughage, CC = carbohydrate concentrate, PC = protein concentrate; label prohibits feeding peanut hay and soybean forage to

livestock. 

2

 From revised Table 1 (J. Stokes, HED; June-2008).

3

 Beef/dairy cattle dietary burden = residue x % diet ÷ % dry matter; poultry/swine dietary burden = residue x (% diet ÷ 100).

.
Tetraconazole Residue Chemistry Summary Document D382300

page 12 of 24

Table 6: Livestock Residues.

matrix max tetraconazole residue from feeding study1

(ppm) tetraconazole transfer coeffcients2

estimated residue at 1x 

MRBDB3

lowest dietary burden middle dietary burden highest dietary burden lowest dietary burden middle dietary burden highest dietary burden

dairy cattle MRBDB = 1.292 ppm (0.3x, 0.8x, 2.6x); hog MRBDB = 0.035 ppm (10x, 29x, 97x)

milk4<0.003 0.016 0.048 -- 0.016 0.014 0.021

skimmed milk <0.003 <0.003 0.003 -- -- 0.0009 0.001

cream 0.023 0.125 0.391 0.068 0.122 0.115 0.158

subcutaneous fat 0.003 0.033 0.205 -- 0.032 0.060 beef = 0.041

swine = 0.001

peritoneal fat 0.029 0.069 0.199 0.085 0.068 0.059 beef = 0.110

swine = 0.003

kidney 0.007 0.039 0.067 0.021 0.038 0.020 beef = 0.049

swine = 0.001

liver 0.371 0.662 1.636 1.091 0.649 0.481 beef = 1.410

swine = 0.038

muscle <0.003 0.006 0.015 -- 0.006 0.004 beef = 0.008

swine = 0.0002

poultry (MRBDB = 0.050 ppm; 1.4x, 4.8x, 14x)

liver 0.011 0.029 0.081 0.159 0.120 0.113 0.008

kidney <0.01 <0.01 0.049 -- -- 0.069 0.003

skeletal muscle <0.01 <0.01 0.021 -- -- 0.029 0.001

abdominal fat 0.045 0.140 0.456 0.652 0.581 0.639 0.033

skin and 

subcutaneous fat 0.019 0.044 0.181 0.275 0.183 0.253 0.014

egg50.011 0.034 0.135 0.159 0.141 0.189 0.009

1

 Ruminant feeding study - D254411, W. Donovan, 18 May-2000 (dietary burdens of 0.34 ppm, 1.02 ppm, and 3.4 ppm); poultry feeding study - 46614307.der.wpd (dietary burdens of 0.069 ppm, 

0.241 ppm, and 0.714 ppm).

2

 Transfer coefficient = tetraconazole residue ÷ dietary burden.

3

 Residue estimate = dietary burden x transfer coefficient; the highest transfer coefficient derived from a dosing level which resulted in quantifiable residues was used; since the dairy cattle MRBDB is 

higher than that for beef, it was used to estimate residues in ruminant tissue.

4

 Residues in milk peaked on the third day of dosing.

5

 Residues in egg peaked on the tenth day of dosing.
Tetraconazole Residue Chemistry Summary Document D382300

page 13 of 24

OPPTS 860.1500 - Crop Field Trials: 

48135102.der1.docx (field corn); 48131301.der.docx (strawberry); 47270101.der.doc (grape)

The petitioners requested registration for application of Mettle 125ME Fungicide (ME; 1 lb 

ai/gallon; EPA Reg. No. 80289-8) to the small fruit vine climbing (except fuzzy kiwifruit) subgroup 

13-07F and the low-growing berry subgroup 13-07G (except cranberry) and Domark®230ME 

Fungicide (ME; 1.9 lb ai/gallon; EPA Reg. No. 80289-7) to popcorn and field corn (including field 

corn grown for seed). Below are HED’s conclusions concerning the adequacy of the field trial data 

submitted in support of these proposals. HED notes that the submitted field trial studies monitored 

for residues of tetraconazole, T, TA, and TAA; information concerning the magnitude of the 

remaining residues of concern can be found in the dietary exposure (D381912, T. Bloem, 14-Apr2011) and/or risk assessment (D380618, A. Nowotarski et al., in draft) documents.

Small Fruit Vine Climbing (except fuzzy kiwifruit) Subgroup 13-07F: HED previously approved a 

petition for application of tetraconazole to grape, the representative crop for the 13-07F subgroup, 

and recommended for a 0.20 ppm tolerance for residues of tetraconazole per se (D384213, T. Bloem, 

13-Jan-2011). The grape field trials were geographically distributed as suggested in Table 5 of 

860.1500, were conducted with the proposed formulation, and employed the proposed application 

scenario (see below for a summary of these data). HED notes that the field trials did not include an 

adjuvant in the spray solution. Provided a revised Section B is submitted prohibiting the addition of 

adjuvants to the spray solutions for 13-07F crops, HED concludes that a tolerance of 0.20 ppm for 

residues of tetraconazole per se in/on the small fruit vine climbing (except fuzzy kiwifruit) subgroup 

13-07F is appropriate. The currently established grape tolerance should be deleted. A revised 

Section F is requested,

Low-growing Berry Subgroup 13-07G (except cranberry): As part of the current submission, IR-4

submitted adequate strawberry field trial data (strawberry is the representative crop for the 13-07G 

subgroup; see below for summary). The field trials were geographically distributed as suggested in 

Table 5 of 860.1500, were conducted with the proposed formulation, and employed the proposed 

application scenario. HED notes that the field trials did not include an adjuvant in the spray solution. 

The tetraconazole residue data were entered in the tolerance spreadsheet as specified by the 

Guidance for Setting Pesticide Tolerances Based on Field Trial Data (see attachment 2) with a 

resulting recommended tolerance of 0.25 ppm. Provided a revised Section B is submitted 

prohibiting the addition of adjuvants to the spray solutions for 13-07F crops and with elimination of 

the application instructions for cranberry (see next paragraph), HED concludes that a tolerance of 

0.25 ppm for residues of tetraconazole per se in/on the low-growing berry subgroup 13-07G (except 

cranberry) is appropriate (T, TA, and TAA storage stability data are required to validate the field trial 

data; see Section 860.1380). A revised Section F is requested.

IR-4 initially requested a Section 3 Registration for application to the entire low-growing berry

subgroup 13-07G. Since it was evident that residues in water from the cranberry use would alone 

result in dietary exposures greater than HED’s level of concern, IR-4 submitted a letter and revised 

Section F withdrawing the request for a tolerance on cranberry as part of the 13-07G subgroup. A 

revised Section B was not submitted. 
Tetraconazole Residue Chemistry Summary Document D382300

page 14 of 24

Field Corn and Popcorn: As part of the current submission, Isagro submitted field corn field trial 

data (see below for summary; field corn is an acceptable surrogate for popcorn). The field trials 

were geographically distributed as suggested in Table 5 of 860.1500, were conducted with the 

proposed formulation, and employed the proposed application scenario. HED notes that the field 

trials included a nonionic surfactant (NIS) or crop oil concentrate (COC) in the spray solution. The 

tetraconazole residue data were entered in the tolerance spreadsheet as specified by the Guidance for 

Setting Pesticide Tolerances Based on Field Trial Data (see attachment 2); the resulting 

recommended tolerances are as follows (field corn grain data were not entered as all residues were 

<LOQ; grain (tetraconazole), stover/forage (tetraconazole and T) storage stability data are required to 

validate the field trial data; see Section 860.1380): corn, field, grain - 0.01 ppm; corn, field, forage -

1.1 ppm; corn, field, stover - 1.7 ppm; corn, pop - 0.01 ppm; and corn, pop, stover - 1.7 ppm. A 

revised Section F is requested.

The field corn and popcorn label prohibits application after the R3 crop growth stage with no 

specified PHIs. Since the R3 crop growth stage represents a mid-season application and the field trial 

data employed application at the R3 crop growth stage (forage, grain, and stover samples were 

collected at the normal harvest time), HED concludes that proposed label is adequate and PHIs are 

unnecessary. 

Grape (47270101.der.doc): Twelve field trials were conducted in North American Free Trade 

Agreement (NAFTA) Growing Zones 1 (n=2), 10 (n=8), and 11 (n=2). Each field trial consisted of a 

single control plot and two treated plot (plots A and B). Treatment plots A and B received two foliar 

applications (RTI = 14-16 days) of a ME tetraconazole formulation (1.04 lb ai/gal) at ~0.040 lb 

ai/acre (1x proposed single/seasonal rate; adjuvants were not added). Treatment plot A received the 

first application 43-47 days prior to harvest and samples were harvested 28-32 days after the last 

application (DALA). Treatment plot B received the first application 28-32 days prior to harvest and 

samples were harvested 14-16 DALA (proposed PHI). At one of the field trial sites, additional 

samples were harvested from treatment plots A (0, 7, 15, 22, and 37 DALA) and B (0, 5, 10, and 22 

DALA). 

The samples were analyzed for residues of tetraconazole, T, TA, and TAA using adequately

validated methods (only samples from treatment B plot were analyzed for T, TA, and TAA). Table 7

is a summary of the residues in/on the treated samples. The residue decline data indicated that 

tetraconazole per se residues decreased with increasing PHI (T, TA, and TAA residues were <LOQ 

at all intervals). 

Strawberry (48131301.der.docx): Eight field trials were conducted in NAFTA Growing Zones 1 

(n=1), 2 (n=1), 3 (n=1), 5 (n=1), 10 (n=3), and 11 (n=1). In addition, two greenhouse trials were 

conducted in the United States encompassing NAFTA Growing Zones 6 and 9. Except for the 

greenhouse trial conducted in Growing Zone 9, the trials employed four foliar applications of a ME 

tetraconazole formulation (1.0 lb ai/gal) at 0.0430-0.0463 lb ai/acre (1x proposed single/seasonal 

rate; adjuvants were not added). The CO greenhouse trial employed four foliar applications of a ME 

tetraconazole formulation (1.0 lb ai/gal) at 0.0206-0.0212 lb ai/acre (0.5x proposed single/seasonal 

rate). The RTIs were 12-16 days for all except between the third and fourth application at the NY 

trial which was conducted with a RTI of 8 days due to rapidly maturing strawberries. Strawberry

samples were harvested at 0 and 1 day after the last application. A decline trial was carried out and 

samples were also harvested at 4-, 7-, and 14-day PHIs.
Tetraconazole Residue Chemistry Summary Document D382300

page 15 of 24

The samples were analyzed for residues of tetraconazole, T, TA, and TAA using adequately

validated methods. Table 7 is a summary of the residue data (CO greenhouse trial is not included in 

the summary). In the decline trial, maximum residue of tetraconazole was 0.09 ppm at 0 and 1 day, 

and <0.05 ppm at 4, 7, and 14 days (residues of T, TA, and TAA were <LOQ at all intervals in the 

residue decline trial). Tetraconazole, T, TA, and TAA residues were <LOQ in the CO greenhouse 

trial which employed four applications at 0.0206-0.0212 lb ai/A (PHI = 0 and/or 1 day). Data 

demonstrating the stability of T, TA, and TAA residues in/on strawberry (516 days) should be 

submitted. 

Field Corn (48135102.der1.docx): Twenty-one field trials were conducted in NAFTA Growing 

Zones 1 (n=1), 2 (n=1), 4 (n=1), 5 (n=17), and 6 (n=1). The trials employed a single broadcast 

application of a ME tetraconazole formulation (1.9 lb ai/gal) at 0.091 lb ai/acre (1x the proposed 

single/seasonal rate). All applications included either a COC or a NIS in the spray solution. Field 

corn forage, grain, and stover were harvested from each plot at commercial harvest maturity. At three 

trial sites (MS, IL, and IA), additional samples of forage, grain, and stover were harvested at 7 and 3 

days prior to normal harvest, at normal harvest, and at 3 and 7 days after normal harvest to assess 

residue decline. 

The samples were analyzed for residues of tetraconazole, T, TA, and TAA using adequately

validated methods. Samples from the individual trials were analyzed for T, TA, and TAA excluding 

the 12 trials conducted in Growing Zone 5 where a composite blended sample was analyzed. Table 7

is a summary of the residue data. The tetraconazole residue decline data for field corn forage and 

stover did not result in a discernable pattern (residues were variable over the sampling interval) while 

resides in field corn grain were <LOQ at all sampling intervals. The following storage stability data 

should be submitted: tetraconazole in corn grain, forage, and stover (266 days) and T in corn forage 

and stover (263 days). HED notes that MRID 47606601, which presents information concerning the 

stability of T, TA, and TAA in several matrices, has been submitted to the Agency but has not yet 

been reviewed. Provided these data demonstrate the stability of T, TA, and TAA in the above 

matrices, no additional information will be required for these analytes. 
Tetraconazole Residue Chemistry Summary Document D382300

page 16 of 24

Table 7: Summary of Residue Data from Crop Field Trials.

Commodity Total Rate

(lb ai/acre)

PHI

(days)

Residue Levels (ppm)2

n Min. Max. HAFT3 Median Mean Std. Dev.

Tetraconazole

Grape1 plot A - ~0.080 28-31 24 <0.01 0.091 0.056 0.013 0.022 0.019

plot B - ~0.080 14-16 24 <0.01 0.096 0.095 0.019 0.031 0.027

Strawberry 0.174–0.182

0 18 <0.05 0.21 0.20 0.08 0.091 0.047

1 18 <0.05 0.18 0.16 0.07 0.086 0.044

Corn forage

0.088-0.094

7-30 42 0.041 0.962 0.907 0.401 0.2

Corn grain 48-95 42 <0.01 <0.01 <0.01 <0.01 <0.01 --

Corn stover 56-107 42 <0.01 1.722 1.548 0.453 0.3

T

Grape plot B - ~0.080 15 24 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01

Strawberry 0.174–0.182

0 2 <0.01 <0.01 <0.01 <0.01 <0.01 --

1 18 <0.01 <0.01 <0.01 <0.01 <0.01 --

Corn forage

0.088-0.094

7-30 42 <0.01 0.019 0.015 0.010 0.0

Corn grain 48-95 15 <0.01 <0.01 <0.01 <0.01 <0.01 --

Corn stover 56-107 42 <0.01 0.060 0.035 0.011 0.0

TA

Grape plot B - ~0.080 15 24 <0.01 0.053 0.051 0.01 0.016 0.012

Strawberry 0.174–0.182

0 2 <0.01 <0.01 <0.01 <0.01 <0.01 --

1 18 <0.01 0.041 0.039 <0.01 0.015 0.010

Corn forage

0.088-0.094

7-30 42 0.018 0.286 0.272 0.083 0.1

Corn grain 48-95 15 0.075 1.151 1.106 0.456 0.4

Corn stover 56-107 42 <0.01 0.663 0.510 0.075 0.1

TAA

Grape plot B - ~0.080 15 24 <0.01 0.017 0.016 0.01 0.011 0.002

Strawberry 0.174–0.182

0 2 <0.01 <0.01 <0.01 <0.01 <0.01 --

1 18 <0.01 <0.01 <0.01 <0.01 <0.01 --

Corn forage

0.088-0.094

7-30 42 <0.01 0.025 0.021 0.013 0.0

Corn grain 48-95 15 <0.01 0.022 0.022 0.013 0.0

Corn stover 56-107 42 <0.01 0.060 0.039 0.014 0.0

1

 Plots A and B both received two (RTI = 14-16 days) airblast applications of the 125 g/L tetraconazole formulation (1.04 lb ai/gal; 

EC) at ~0.04 lb ai/acre (1x). Plot A received the first application 43-47 days prior to normal harvest while plot B received the first 

application 28-32 days prior to normal harvest. Only samples from plot B were analyzed for T, TA, and TAA.

2

 The median, mean, and standard deviation were calculated assuming LOQ residues for residues <LOQ. 

3

 HAFT = highest-average field trial.

OPPTS 860.1520 - Processed Food/Feed: 

47270101.der.doc (grape); 48135102.der2.docx (field corn)

The petitioner previously submitted a grape processing study (47270101.der.doc; D353020, T. Bloem, 

26-June-2008) and submitted a field corn processing study as part of the current petition 

(48135102.der2.docx). The grape study indicated that residues of tetraconazole per se do not 

concentrate in grape juice or raisin (conducted at 5x seasonal rate). The corn processing study resulted 

in tetraconazole per se residues <LOQ in both the RAC and processed commodities (conducted at 5x 

seasonal rate); therefore, processing factors could not be calculated. Based on these data, HED 

concludes that tolerances for the grape and field corn processed commodities are unnecessary. The 

grape and field corn processing studies also monitored for residues of T, TA, and TAA and these data, 

as well as the tetraconazole data, are summarized below. Information concerning the magnitude of the 

remaining residues of concern can be found in the dietary exposure (D381912, T. Bloem, 14-Apr-2011) 

and/or risk assessment (D380618, A. Nowotarski et al., in draft) documents. Storage stability data are 
Tetraconazole Residue Chemistry Summary Document D382300

page 17 of 24

required to validate field corn (tetraconazole, T, TA, and TAA) processing studies (see Section 

860.1380). 

HED notes the field corn aspirated grain fraction residue data were not provided. Residues of 

tetraconazole and T were <LOQ in/on all the field corn grain samples thereby eliminating the need for 

aspirated grain fraction residue data for these analytes (see guidance for OPPTS 860.1000 Table 1 

Feedstuff Revisions, J. Stokes, June-2008). However, residues of TA (0.456 ppm) and TAA (0.013 

ppm) were found in/on corn grain; HED does have soybean aspirated grain fraction data (2 x 0.09+ lb 

ai/acre R3-R5 crop stage) which did not demonstrate significant concentration of T, TA, or TAA 

residues in the aspirated grain fractions. Since aspirated grain fractions are a minor feed commodity, 

HED concludes that the soybean aspirated grain fraction T, TA, and TAA residue are an adequate 

surrogate for field corn. 

Grape (47270101.der.doc): Two field trials were established during 2006 in NAFTA growing zones 

10 and 11. The treated plots received two applications (RTI = 14-15 days) of a 125 g/L liquid 

tetraconazole formulation at ~0.200 lb ai/acre (5x). The first application was made 28-32 days prior to 

harvest and bulk grape samples were harvested 14-16 days after the last application. The bulk grape 

samples (n=2) were processed into grape juice (cold press) and raisin (<14% moisture) using simulated 

commercial processing procedures. The resulting samples were analyzed for tetraconazole, T, TA, and 

TAA residues using adequately validated methods. Table 8 is a summary of the tetraconazole, T, TA, 

and TAA processing factors. 

Field Corn (48135102.der2.docx): Two field trials were established during 2009 in NAFTA growing 

zones 5 and 6. The treated plots received a single application of a ME tetraconazole formulation (1.9 

lb ai/gal) at 0.452-0.457 lb ai/A (R3 crop stage; 5x). Field corn grain was harvested at commercial 

harvest maturity and processed into starch, refined oil (wet and dry milling), grits, flour, and meal 

using simulated commercial procedures. The resulting samples were analyzed for residues of 

tetraconazole, T, TA, and TAA using adequately validated methods. Table 8 is a summary of the 

tetraconazole, T, TA, and TAA processing factors. Data demonstrating the stability of tetraconazole 

in/on field corn grain (266 days) and refined oil (198 days) and T, TA, and TAA in/on refined field 

corn oil (198 days) should be submitted. HED notes that MRID 47606601, which presents 

information concerning the stability of T, TA, and TAA in several matrices, has been submitted to the 

Agency but has not yet been reviewed. Provided these data demonstrate the stability of T, TA, and 

TAA in the above matrices, no additional information will be required for these analytes. 
Tetraconazole Residue Chemistry Summary Document D382300

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Table 8: Residue Data from Grape and Field Corn Processing Studies.

Crop Commodity Total Rate

(lb ai/A)

PHI

(days)

Residues (ppm) Processing Factor1,2

Tetracona

zole TA TAA T

Tetracona

zole TA TAA T

Traver, CA; 2006; CA4; 10

Grape

Grape (RAC)

~0.40 15

0.077 <0.01 <0.01 <0.01 -- -- -- --

Juice 0.008 <0.01 <0.01 <0.01 0.01 NC NC NC

Raisin 0.070 <0.01 <0.01 <0.01 0.91 NC NC NC

Ephrata, WA; 2006; WA1; 11

Grape 

Grape (RAC)

~0.40 14

0.579 <0.01 <0.01 <0.01 -- -- -- --

Juice 0.035 <0.01 <0.01 <0.01 0.06 NC NC NC

Raisin 0.411 0.020 <0.01 <0.01 0.71 >2.0 NC NC

Richland, IA; 2009 (22P; V-32894-V)

Field 

Corn

Grain (RAC)

~0.45 89

<0.01 0.906 <0.01 <0.01 -- -- -- --

Starch <0.01 0.030 <0.01 <0.01 NC 0.03x NC NC

Refined oil (wet milling) <0.01 <LOQ <0.01 <0.01 NC <0.01x NC NC

Grits <0.01 0.491 <0.01 <0.01 NC 0.5x NC NC

Flour <0.01 0.387 <0.01 <0.01 NC 0.4x NC NC

Meal <0.01 0.527 <0.01 <0.01 NC 0.6x NC NC

Refined oil (dry milling) <0.01 0.016 <0.01 <0.01 NC 0.02x NC NC

Hinton, OK; 2009 (23P; V-32894-X)

Field 

Corn

Grain (RAC)

~0.45 50

<0.01 0.436 <0.01 <0.01 -- -- -- --

Starch <0.01 0.023 <0.01 <0.01 NC 0.05x NC NC

Refined oil (wet milling) <0.01 <0.01 <0.01 <0.01 NC <0.02x NC NC

Grits <0.01 0.172 <0.01 <0.01 NC 0.4x NC NC

Flour <0.01 0.160 <0.01 <0.01 NC 0.4x NC NC

Meal <0.01 0.220 <0.01 <0.01 NC 0.5x NC NC

Refined oil (dry milling) <0.01 0.013 <0.01 <0.01 NC 0.03x NC NC

1

 NC = Not calculated; residues were below the LOQ (<0.01 ppm for all in analytes) in both RAC and processed fraction.

2

 Processing Factor = (residue in the processed fraction) ÷ (residue in the RAC). 

860.1850 and 860.1900 Confined/Field Accumulation in Rotational Crops

Based on the results of the confined rotational crop studies and toxicological considerations, HED 

concluded that the residue of concern in rotational crops for tolerance enforcement is tetraconazole per se

and the residues of concern for risk assessment are tetraconazole, M14360-acid, M14360-DFA, M14360(C1)-alcohol (free and conjugated), and TA, THP, and TAA and all labile conjugates of these compounds (for 

a full discussion see D331476, M. Clock-Rust et al., 26-Jan-2007). The petitioner has submitted data 

concerning the magnitude of tetraconazole per se residues in rotational crops and these data are summarized 

below.

A field rotational crop study has been previously submitted which monitored for residues of tetraconazole 

per se in spring wheat (straw and grain), peas (seed), potato (tuber), canola (seed), and sugar beet (root and 

top) planted 7-9 days following application of tetraconazole to bare soil at 0.112 lb ai/acre, 0.223 lb ai/acre, 

0.669 lb ai/acre, and 1.34 lb ai/acre (D278236, W. Donovan, 22-Oct-2001). These application rates 

represent 1.2x, 2.5x, 7.4x, and 15x the seasonal rate for field corn and popcorn; 1.4x, 2.8x, 8.4x, and 17x the 

seasonal rate for 13-07F crops; and 0.7x, 1.4x, 4.2x, 8.4x the seasonal rate for 13-07G crops. Residues of 

tetraconazole per se were <0.02 ppm (<LOQ) in all samples except spring wheat straw harvested from the 

7.4x/8.4x/4.2x and 15x/17x/8.4x treated plots (<0.02-0.05 ppm). 

A supplemental field rotational crop study was also submitted which provided tetraconazole per se residues 

in rotational crops planted in fields in which the primary crop was treated with 2-4 applications of 

tetraconazole at 0.11 lb ai/acre for three consecutive years (2.8-5.5x, 1.4-2.8x, and 2.4-4.9x the 13-07F, 13-
Tetraconazole Residue Chemistry Summary Document D382300

page 19 of 24

07G, and field/pop corn seasonal application rates, respectively; MRID 45320902). In this study, the 

plantback intervals (PBIs) ranged from 76-328 days and the rotational crops were barley, onion, canola, 

bean, pea, potato, and sugar beet. In all rotational crop samples analyzed, tetraconazole per se residue levels 

were below the LOD of 0.01 ppm (D278236, W. Donovan, 22-Oct-2001). 

Based on these data, the proposed PBIs, and proposed application rates, HED concludes that residues of 

tetraconazole per se in rotational crops planted in fields treated at the proposed rate will be insignificant. 

Information concerning the magnitude of the remaining residues of concern can be found in the dietary

exposure (D381912, T. Bloem, 14-Apr-2011) and/or risk assessment (D380618, A. Nowotarski et al., in 

draft) documents.

OPPTS 860.1550 Proposed and HED Recommended Tolerances

Table 9 is a summary the proposed and HED-recommended tolerances for residues of tetraconazole per se

(40 CFR 180.557). A revised Section F is requested specifying the correct tolerance expression (see below), 

commodity definition, and/or tolerance levels. HED notes that there are no Canadian or Codex maximum 

residue limits for tetraconazole; therefore, harmonization is not an issue. HED recommends that the 

tetraconazole tolerance expression be changed to the following (40 CFR 180.557(a)): 

180.557(a): Tolerances are established for residues of tetraconazole, including its metabolites and degradates, in or 

on the commodities listed below. Compliance with the following tolerance levels is to be determined by measuring 

only tetraconazole (1-[2-(2,4-dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy)propyl]-1H-1,2,4-triazole).

Table 9. Tolerance Summary.

Commodity Proposed 

Tolerance (ppm)

HED-Recommended 

Tolerance (ppm) Comments

Small fruit vine climbing, except fuzzy kiwifruit, subgroup 13-07F 0.20 0.20

A revised Section 

F is requested. 

Low-growing berry subgroup 13-07G (except cranberry) 0.25 0.25

Corn, field, forage 1.0 1.1

Corn, field, grain 0.01 0.01

Corn, field, stover 1.5 1.7

Corn, pop, grain 0.01 0.01

Corn, pop, stover 1.5 1.7

Milk Not proposed 0.03

Milk, fat Not proposed 0.75

Fat (cattle, goat, horse, sheep) Not proposed 0.15

Liver (cattle, goat, horse, sheep) Not proposed 1.5

Meat byproducts, except liver (cattle, goat, horse, sheep) Not proposed 0.15

Poultry, meat byproducts Not proposed 0.05

RDI: RAB1 chemists (9-Feb-2011)

T. Bloem:S10945:PY1:(703)-605-0217

Attachment 1: Chemical Structures

Attachment 2: Tolerance Calculations

Attachment 3: International Residue Limit Status
Tetraconazole Residue Chemistry Summary Document D382300

page 20 of 24

Attachment 1: Chemical Structures

Common Name; Chemical Name Structure

Tetraconazole

CAS: 1-[2-(2,4-dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy)

propyl]-1H-1,2,4-triazole

IUPAC: (±)-2-(2,4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-

yl)propyl 1,1,2,2-tetrafluoroethyl ether

N

N

N

OCF2CF2H

Cl

Cl

Triazole (T)

1,2,4-triazole N

N

HN

Triazolyl alanine (TA)

3-(1H-1,2,4-triazol-1-yl)alanine N

N

N NH2

O OH

Triazolyl acetic acid (TAA)

(1H-1,2,4-triazol-1-yl)acetic acid 

N

N

N

HOOC

Triazolyl hydroxypropionic acid (THP)

2-hydroxy-3-(1H-1,2,4-triazol-1-y)propionic acid

N

N

N

OH

HOOC

M14360-acid

2-(2,4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-yl)-propionic acid

N

N

N

Cl

Cl

COOH

M14360-difluoroacetic acid (M14360-DFA)

5-(2,4-dichlorophenyl)-2,2-difluoro-6-(1H-1,2,4-triazol-1-yl)-

oxahexanoic acid

N

N

N

OCF2COOH

Cl

Cl

M14360-alcohol

2-(2,4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-yl)-1-propanol

N

N

N

OH

Cl

Cl
Tetraconazole Residue Chemistry Summary Document D382300

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Attachment 2: Tolerance Calculations (MLE spreadsheet and Tolerance Calculations)

Strawberry

Regulator: EPA

Chemical: tetraconaozle

Crop: strawberry

PHI:

App. Rate:

Submitter:

n: 18

min: 0.05

max: 0.21

median: 0.08

average: 0.09

95th Percentile 99th Percentile 99.9th Percentile

0.20 0.20 0.25

(0.25) (0.25) (--)

0.20 0.25 0.35

(0.25) (0.40) (--)

0.25

0.25

0.45

0.9167

p-value > 0.05 : Do not reject lognormality assumption

Approximate 

Shapiro-Francia 

Normality Test 

EU Method I

Normal

UCLMedian95th

95/99 Rule

EU Method II

Distribution-Free

Mean+3SD
Tetraconazole Residue Chemistry Summary Document D382300

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Corn Forage

Regulator: EPA

Chemical: tetraconaozle

Crop: field corn forage

PHI:

App. Rate:

Submitter:

n: 42

min: 0.04

max: 0.96

median: 0.38

average: 0.41

95th Percentile 99th Percentile 99.9th Percentile

0.80 1.0 1.2

(0.90) (1.1) (--)

1.1 1.7 3.0

(1.5) (3.0) (--)

1.1

1.1

1.9

0.9082

p-value <= 0.01: Reject lognormality assumption

Approximate 

Shapiro-Francia 

Normality Test 

EU Method I

Normal

UCLMedian95th

95/99 Rule

EU Method II

Distribution-Free

Mean+3SD
Tetraconazole Residue Chemistry Summary Document D382300

page 23 of 24

Corn Stover

Regulator: EPA

Chemical: tetraconaozle

Crop: field corn stover

PHI:

App. Rate:

Submitter:

n: 42

min: 0.01

max: 1.72

median: 0.42

average: 0.50

95th Percentile 99th Percentile 99.9th Percentile

1.2 1.5 1.8

(1.4) (1.7) (--)

2.5 5.0 12

(4.0) (10) (--)

1.3

1.7

2.5

0.8086

p-value <= 0.01: Reject lognormality assumption

Approximate 

Shapiro-Francia 

Normality Test 

EU Method I

Normal

UCLMedian95th

95/99 Rule

EU Method II

Distribution-Free

Mean+3SD
Tetraconazole Residue Chemistry Summary Document D382300

page 24 of 24

Attachment 3: International Residue Limit Status

Tetraconazole (120603; 19-January-2011)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

40 CFR 180.557(a): tetraconazole (1-[2-(2,4-dichlorophenyl)-3-

(1,1,2,2-tetrafluoroethoxy)propyl]-1H-1,2,4-triazole) None None

Tolerance (ppm) /Maximum Residue Limit (mg/kg)

Commodity1 US Canada Mexico2 Codex

Corn, field, forage 1.1

Corn, field, grain 0.01

Corn, field, stover 1.7

Corn, pop, grain 0.01

Corn, pop, stover 1.7

Small fruit vine climbing, except fuzzy kiwifruit subgroup 

13-07F 0.20

Low-growing berry subgroup 13-07G 0.25

Milk 0.03

Milk, fat 0.75

Fat (cattle, goat, horse, sheep) 0.15

Liver (cattle, goat, horse, sheep) 1.5

Meat byproducts, except liver (cattle, goat, horse, sheep) 0.15

Poultry, meat byproducts 0.05

Completed: M. Negussie; 01/19/2011

1

Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and not those 

proposed by the applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest 

treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs 

indicated as proposed have not been finalized by the CCPR and the CAC.