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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

 OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

Date: May 24, 2011

MEMORANDUM

SUBJECT: Metconazole: Human Health Risk Assessment for Proposed Uses on Tuberous 

and Corm Vegetables Subgroup 1C and Bushberry Subgroup 13-07B.

PC Code: 125619 DP Barcode: D380512

Decision No.: 436782 Registration No.: 59639-147

Petition No.: 0E7743 Regulatory Action: Section 3 Registration 

Risk Assessment Type: Single Chemical/ 

Aggregate

Case No.: NA

TXR No.: NA CAS No.: 125116-23-6

MRID No.: NA 40 CFR: §180.617

FROM: Barry O’Keefe, Senior Biologist

Amelia Acierto, Chemist

Myron Ottley, Senior Toxicologist

Nancy Tsaur, Chemist

Risk Assessment Branch III

Health Effects Division (7509P)

THROUGH: Paula Deschamp, Branch Chief

Risk Assessment Branch III

Health Effects Division (7509P)

TO: Barbara Madden, RM Team 5

Risk Integration, Minor Use, & Emergency Response Branch

Registration Division (7505P)

Introduction

On behalf of Valent U.S.A. Corporation (Valent), the Interregional Research Project No. 4 (IR-4) 

of Rutgers, The State University of New Jersey, is proposing new foliar uses of metconazole on 

bushberries (crop subgroup 13-07B) and tuberous and corm vegetables (crop subgroup 1C). 

The Registration Division (RD) requested that the Health Effects Division (HED) evaluate 

toxicology and residue chemistry data and conduct dietary, aggregate, and occupational exposure 
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and risk assessments, as needed, to estimate the risk to human health that will result from these 

new uses and tolerances.

A summary of the findings and an assessment of human risk resulting from the registered and 

proposed new uses of metconazole are provided in this document. The risk assessment was 

provided by Barry O’Keefe, the hazard characterization by Myron Ottley, the residue chemistry 

data review and the dietary assessment by Amelia Acierto, and the occupational assessment by 

Nancy Tsaur. The drinking water assessment was provided by Faruque Khan of the 

Environmental Fate and Effects Division (EFED).
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Table of Contents

1.0 Executive Summary .......................................................................................................... 5

2.0 Regulatory Conclusions and Recommendations............................................................ 9

2.1 Data Deficiencies/ Conditions of Registration ....................................................... 9

2.2 Tolerance Considerations...................................................................................... 10

2.2.1 Enforcement Analytical Method............................................................... 10

2.2.2 International Harmonization ..................................................................... 10

2.2.3 Recommended Tolerances........................................................................ 11

2.2.4 Revisions to Petitioned-For Tolerances.................................................... 11

2.3 Label Modifications.............................................................................................. 12

3.0 Ingredient Profile ............................................................................................................ 12

3.1 Summary of Proposed Uses.................................................................................. 12

3.2 Structure and Nomenclature ................................................................................. 14

3.3 Physical and Chemical Properties......................................................................... 14

4.0 Hazard Characterization/Assessment........................................................................... 14

4.1 Hazard and Dose-Response Characterization....................................................... 14

4.1.1 Database Summary ................................................................................... 14

4.1.2 Studies Available and Considered ............................................................ 14

4.1.3 Sufficiency of Studies/Data ...................................................................... 15

4.1.4 Toxicological Effects................................................................................ 15

4.1.5 Cancer Classification ................................................................................ 16

4.2 Absorption, Distribution, Metabolism, Excretion (ADME)................................. 16

4.3 FQPA Considerations ........................................................................................... 17

4.4 FQPA Safety Factor for Infants and Children ...................................................... 17

4.5 Hazard Identification and Toxicity Endpoint Selection........................................ 18

4.5.1 Recommendation for combining routes of exposure for risk assessment. 21

4.6 Endocrine Disruption............................................................................................ 21

5.0 Dietary Exposure/Risk Characterization ..................................................................... 22

5.1 Pesticide Metabolism and Environmental Degradation........................................ 22

5.1.1 Metabolism in Primary Crops................................................................... 22

5.1.2 Metabolism in Livestock........................................................................... 22

5.1.3 Drinking Water Residue Profile................................................................ 23

5.1.4 Food Residue Profile................................................................................. 24

5.2 Dietary Exposure and Risk ................................................................................... 29

5.2.1 Acute Dietary Exposure/Risk ................................................................... 30

5.2.2 Chronic Dietary Exposure/Risk ................................................................ 30

5.3 Anticipated Residue and Percent Crop Treated (%CT) Information.................... 30

5.4 Dietary Assessment of Free Triazole and its Conjugates ..................................... 31

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................ 32

6.1 Residential Handler Exposure and Risk Characterization.................................... 33

6.2 Residential Postapplication Exposure and Risk Characterization ........................ 33

7.0 Aggregate Risk Assessments and Risk Characterization............................................ 36

7.1 Acute & Chronic Aggregate Risk......................................................................... 36

7.2 Short- and Intermediate-Term Aggregate Risk..................................................... 36

8.0 Cumulative Risk Characterization/Assessment........................................................... 39

9.0 Occupational Exposure/Risk Pathway.......................................................................... 39
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9.1 Short- and Intermediate-Term Handler Risk ........................................................ 40

9.2 Short-and Intermediate-Term Postapplication Risk.............................................. 42

Appendix A: Toxicology Assessment ....................................................................................... 43

A.1 Toxicology Data Requirements ................................................................................ 43

A.2 Toxicity Profiles........................................................................................................ 44

Appendix B: EPA Review of Human Research ...................................................................... 51

Appendix C: Structure, Nomenclature, and Physical and Chemical Properties................. 51

Appendix D: International Residue Limit Status................................................................... 53
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1.0 Executive Summary

Metconazole (5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)

cyclopentanol) is a broad-spectrum triazole fungicide that works systemically by preventing 

spore formation and inhibiting mycelial growth. Metconazole acts primarily as an inhibitor of 

ergosterol biosynthesis, thereby interfering with synthesis of fungal cell membranes and 

providing systemic seed and seedling protection. 

On behalf of Valent U.S.A. Corporation (Valent), the IR-4 of Rutgers, The State University of 

New Jersey, is proposing two new foliar uses of metconazole on bushberries (crop subgroup 13-

07B) and tuberous and corm vegetables (crop subgroup 1C). The proposed formulated end-use 

product is Metconazole 50 WDG Fungicide (EPA Reg. No. 59639-147). Metconazole 50 WDG 

Fungicide is a water dispersible granule (WDG), containing 50% active ingredient (ai).

Use Profile

Under the proposed use, four foliar applications can be made to tuberous and corm vegetables at 

0.078-0.125 lb ai/A/application for a total maximum seasonal rate of 0.500 lb ai/A and three 

applications will be made to bushberries at 0.078 lb ai/A/application for a total maximum 

seasonal rate of 0.234 lb ai/A. However, a maximum of only two sequential applications are 

allowed for both tuberous and corm vegetables and bushberries. For tuberous and corm 

vegetables the preharvest interval (PHI) is 1 day. For bushberries the PHI is 7 days.

Toxicity/Hazard

The toxicological database for metconazole is sufficient for the purpose of this risk assessment. 

The liver is the primary target organ in the mouse, rat and dog following oral exposure to 

metconazole via subchronic or chronic exposure durations. Other adverse effects observed in 

oral studies were decreased body weight, decreased body weight gains, and blood effects 

(reductions in erythrocyte and/or platelet parameters) in the mouse, rat, dog and/or rabbit. 

Splenic effects including increased spleen weight and hyperplasia were observed in the mouse, 

rat and dog at dose levels where liver effects were also observed. In dogs, lenticular 

degeneration (cataracts) and gastrointestinal irritation were observed at the high dose level(s). 

Developmental studies in rats and rabbits show evidence of developmental effects, but only at 

dose levels that are maternally toxic. There is qualitative evidence of susceptibility in the rat 

developmental study, however the concern is low since the developmental effects are wellcharacterized, occur in the presence of maternal toxicity, the NOAELs are well defined, and the 

dose/endpoint is used for acute dietary risk assessment for the sensitive population. Metconazole 

did not demonstrate the potential for neurotoxicity in the four species (mouse, rat, dog and 

rabbit) tested. Metconazole is considered nongenotoxic and is classified as "not likely to be 

carcinogenic to humans" at levels that do not cause mitogenesis. In accordance with the revised 

40 CFR Part 158 data requirements, an immunotoxicity study and a neurotoxicity battery are 

required. The existing database includes a recently submitted and reviewed immunotoxicity 

study, and a subchronic neurotoxicity study, but not an acute neurotoxicity study, and this 

remains a data deficiency. 
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Drinking Water

A drinking water assessment for the proposed uses on the tuberous/corm vegetables and 

bushberry were performed using PRZM/EXAMS modeling. Estimated drinking water 

concentrations (EDWCs) of metconazole in drinking water from use on the existing and new 

crops were provided by EFED and incorporated directly into the acute and chronic dietary 

assessments. The EDWCs are based on the maximum proposed rates specified on the label. For 

surface water, the highest acute EDWC is 45.48 μg/L from the existing use on turf, and the 

highest chronic EDWC is 38.16 μg/L from the cranberry use scenario. For ground water, the 

acute and chronic EDWC is 0.38 μg/L from the existing use on turf.

Dietary Exposure (food and drinking water)

Unrefined dietary (food and drinking water) exposure analyses were performed using DEEMFCIDTM that indicate that acute and chronic dietary exposure to metconazole from food and 

drinking water are well below HED’s level of concern (LOC) for metconazole. The estimated 

acute exposure of females 13-49 years old, the only population subgroup of concern for acute 

exposure, represents 3.8% of the aPAD at the 95th percentile of exposure. The chronic dietary 

(food + drinking water) exposure to metconazole is below HED’s level of concern for the 

general U.S. population and all population subgroups. The chronic dietary exposure utilized 6% 

cPAD for the general U.S. population and <13% of the cPAD for children 1-2 years old, the most 

highly exposed population subgroup.

Dietary Assessment of Free Triazole and its Conjugates

Metconazole is among the group of pesticides which generate the common triazole metabolites 

1,2,4-triazole (T), triazolylalanine (triazole alanine; TA), triazolylacetic acid (triazole acetic acid; 

TAA), and triazolylpyruvic acid (TP). These triazole residues have been evaluated for the entire 

class of triazole compounds. HED has previously completed a comprehensive risk assessment 

considering these common triazole metabolites based on established and proposed uses of 

triazole fungicides as of 1-September-2005 (DP322215, M. Doherty et al., 2/7/06). In 

connection with pending new uses, HED has revised the triazole dietary assessment to include 

the new uses of metconazole and has determined that aggregate risk (food, water and residential) 

remains below HED’s level of concern (DP388469, T. Morton, 4/27/11). There are no dietary 

exposure considerations for the common triazole metabolites that would preclude granting the 

registration requests.

Residential Exposure

This document presents the assessment of the proposed new agricultural uses of metconazole. No new 

residential uses are being requested at this time. However, adults, adolescents and children may be 

exposed to metconazole from its currently registered use on turf and ornamentals.
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Aggregate Risk

Dietary, incidental oral and inhalation routes of exposure have the same toxicity endpoints, and 

therefore, can be aggregated. Acute and chronic aggregate risk assessments include only food 

and drinking water, and the results are covered in the dietary section of this executive summary.

The short- and intermediate-term aggregate risk assessments for metconazole take into account 

average (chronic) exposure estimates from dietary consumption of metconazole (food and 

drinking water) and non-occupational/residential use on turf (inhalation for adults, and incidental 

oral for children). Postapplication exposures from the use on turf are considered predominantly 

short-term (1-30 days). Although exposures are expected via the dermal route, quantification of 

dermal risk was not conducted, since a dermal endpoint was not identified for short-, or 

intermediate-term exposures. Therefore, short- and intermediate-term postapplication aggregate 

risk assessments were conducted only for average dietary and incidental oral exposures to 

children, and average dietary and inhalation exposures to adults.

The short-and intermediate-term aggregate MOEs from dietary exposure (food + drinking water) 

and non-occupational/residential handler exposure (inhalation) for adults are 1700 and 1700, 

respectively, which are not of concern to HED, since these MOEs are greater than the level of 

concern MOE of 100.

The short-and intermediate-term aggregate MOEs from dietary exposure (food + drinking water) 

and non-occupational/residential exposure (incidental oral) for children 1-2 years old are 420 and 

460, respectively; which are not of concern to HED, since these MOEs are greater than the level 

of concern MOE of 100.

These aggregate exposure assessments are considered conservative estimates that should not 

underestimate risks for the following reasons: 1) the dietary inputs used tolerance-level residues, 

100% crop treated, and screening level drinking water modeling data (i.e., Tier II surface water 

modeling); and 2) screening-level residential SOPs and upper level estimates of exposure were 

employed.

Updated Aggregate Assessment of Free Triazole & its Conjugates

As with the dietary assessment, HED has completed an updated aggregate human health risk 

assessment (DP389080, T. Morton, 4/27/11) for 1,2,4-triazole and the conjugated triazole 

metabolites (TA, TAA and TP). The only revisions to the components of the previous aggregate 

exposure and risk estimates are to the dietary exposure estimates. For the common triazole 

metabolites, acute and chronic aggregate risks consist only of dietary components and, therefore, 

are equivalent to the dietary risk estimates. For short- and intermediate-term aggregate 

scenarios, the revised aggregate estimates are below HED’s level of concern.
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Occupational Exposure and Risk

Handlers: Based on the proposed uses, there is a potential for short- and intermediate-term 

occupational exposure to metconazole during handling activities (e.g. mixing, loading, 

application). The results of the occupational handler exposure and risk assessment indicate that 

short- and intermediate-term inhalation risks do not exceed HED’s LOC (i.e. an MOE < 100). 

For short-term exposure, the handler inhalation MOEs ranged from 19,000 to 340,000 at baseline

(i.e., no respirator). For intermediate-term exposure, the handler inhalation MOEs ranged from 

13,000 to 240,000 at baseline.

Postapplication Workers: There is a potential for short- and intermediate-term occupational 

exposure during post-application activities. However, since no dermal endpoint has been 

identified, a dermal post-application assessment is not needed. Under Worker Protection 

Standards (WPS), the 12-hour restricted entry interval (REI) on the label is acceptable.

Environmental Justice Considerations

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, ―Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations,‖ 

http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf.

As a part of every pesticide risk assessment, OPP considers a large variety of consumer 

subgroups according to well-established procedures. In line with OPP policy, HED estimates 

risks to population subgroups from pesticide exposures that are based on patterns of that 

subgroup’s food and water consumption, and activities in and around the home that involve 

pesticide use in a residential setting. Extensive data on food consumption patterns are compiled 

by the USDA under the Continuing Survey of Food Intake by Individuals (CSFII) and are used 

in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed 

and categorized by subgroups based on age, season of the year, ethnic group, and region of the 

country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups 

and exposure assessments are performed when conditions or circumstances warrant. Whenever 

appropriate, nondietary exposures based on home use of pesticide products and associated risks 

for adult applicators and for toddlers, youths, and adults entering or playing on treated areas 

postapplication are evaluated. Further considerations are currently in development as OPP has 

committed resources and expertise to the development of specialized software and models that 

consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary 

patterns among specific subgroups.

Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These studies (listed in Appendix B) have 

been determined to require a review of their ethical conduct, and have received that review.
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2.0 Regulatory Conclusions and Recommendations

Provided revised Sections B (OPPTS 860.1200) and F (OPPTS 860.1550) are submitted, HED

can recommend for a conditional registration and permanent tolerances for the proposed uses of 

metconazole on tuberous and corm vegetable subgroup 1C and the bushberry subgroup 13-07B. 

Additional data are needed as conditions of registration as outlined in Section 2.1 below. The 

specific tolerance recommendations are discussed in Section 2.2, and label modifications are 

discussed in Section 2.3.

2.1 Data Deficiencies/Conditions of Registration

The following must be provided prior to a tolerance being established or registration 

allowed:

860.1200 Directions for Use

Since no spray adjuvants were used in the residue field trials on potatoes and blueberries, 

the label must be amended to include a statement that no adjuvant should be used for the 

tuberous and corm vegetable subgroup 1C and the bushberry subgroup 13-07B.

860.1550 Proposed Tolerances

Section F should be revised to reflect the correct identification of the chemical being 

proposed. Propiconazole appears in Section F as the pesticide proposed. 

The commodity definition for tuberous and corm vegetables must be changed to 

Vegetable, tuberous and corm, subgroup 1C as shown in Table 1.

A revised Section F should be submitted to propose a tolerance of 0.04 ppm for 

Vegetable, tuberous and corm, subgroup 1C and 0.40 ppm for Bushberry subgroup 13-07 

B as shown inTable 1.

The following data are required as conditions of registration:

RESIDUE CHEMISTRY

860.1360 Multiresidue Methods

HED has previously identified the need for metconazole to be tested through OV-17 and 

OV-225 GC columns. This deficiency remains outstanding.

860.1380 Storage Stability

Storage stability data for residues of 1,2,4-triazole, triazolylacetic acid, and 

triazolylalanine have not been submitted in conjunction with the subject petition . 

Although storage stability data for the triazoles are under review by the Agency, more 

data may be required to support this petition.
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TOXICOLOGY

870.6200a Acute Neurotoxicity Study

An acute neurotoxicity study is required in accordance with the revised 40 CFR Part 158 

data requirements, as part of a neurotoxicity battery. The existing database includes a 

subchronic neurotoxicity study, but not an acute neurotoxicity study, and this remains a 

data deficiency. 

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

An adequate gas chromatography method with nitrogen-phosphorus-detection (GC/NPD) is 

available for data collection and enforcement of tolerances for residues of metconazole parent 

isomers (cis- and trans- metconazole) in plant commodities based on Valent Method RM-41C-1, 

―Determination of cis and trans–Metconazole in Crops.‖ An adequate high performance liquid 

chromatography (HPLC) method is available for data collection and enforcement of tolerances 

for residues of 1,2,4-triazole (T), triazole alanine (TA), and triazole acetic acid (TAA). The 

method is based on Morse Laboratories, Inc. analytical method, Meth-160, Rev. 2, 

―Determination of 1,2,4-Triazole, Triazole Alanine and Triazole Acetic Acid Residues in Plants 

and Animal Matrices.‖ The GC/NPD and HPLC methods were adequately validated prior to and 

concurrently with the analyses of the crop field samples. The lowest level of method validation 

(LLMV) in potato was 0.02 ppm for both metconazole and the triazole metabolites, and in 

blueberry, the LLMV is 0.05 ppm for metconazole and 0.02 ppm for the triazole metabolites.

For metconazole residues in potatoes, the calculated limits of detection (LOD) are 0.0037 and

0.0056 ppm for cis and trans-metconazole, respectively. For the triazole metabolites in potatoes, 

the calculated LODs are 0.0052, 0.0066 and 0.0078 ppm for T, TA, and TAA, respectively. For 

metconazole residues in blueberries, the calculated LODs are 0.0012 and 0.0092 ppm for cis and 

trans-metconazole, respectively. For T, TA, and TAA in blueberries the calculated LODs are

0.010, 0.0042 and 0.011 ppm, respectively.

The limit of quantitation (LOQ) is defined as the lowest fortification level of an analyte at which 

acceptable recovery data can be achieved. The LOQ is equivalent to the LLMV. 

Additional multiresidue method testing data required from a previous petition remain 

outstanding for metconazole. It was concluded (DP# 361110) that further work is required to 

test the separation of metconazole on OV-17 and OV-225 columns under Protocol C.

2.2.2 International Harmonization

There are currently no established Codex, Canadian, or Mexican maximum residue limits 

(MRLs) for metconazole on potato or blueberry. An International Residue Limit (IRL) status 

sheet is appended to this document as Appendix D.
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2.2.3 Recommended Tolerances

In accordance with HED’s Interim Guidance on Tolerance Expressions (5/27/09, S. Knizner), the 

tolerance expression for metconazole should be stated as follows:

Tolerances are established for residues of metconazole, including its metabolites and 

degradates, in or on the commodities in the table below. Compliance with the tolerance 

levels specified below is to be determined by measuring only metconazole [5-[(4-

chlorophenyl)methyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)cyclopentanol] as the 

sum of its cis- and trans-isomers.

The proposed uses and the submitted data support the following tolerances for residues of 

metconazole on/on the following raw agricultural commodities.

Bushberry subgroup 13-07B....................................0.40 ppm

Vegetable, tuberous and corm, subgroup 1C...........0.04 ppm

2.2.4 Revisions to Petitioned-For Tolerances

Permanent tolerances have been proposed by IR-4 for the combined residues of the fungicide 

metconazole in/or on the tuberous and corm vegetables subgroup 1C at 0.02 and the bushberry 

subgroup 13-07B at 0.35 ppm. 

For purposes of the tolerance expression, HED has determined that the residue of concern is 

metconazole (the sum of cis- and trans- isomers) for both primary and rotational crops and for 

livestock commodities. The tolerance expression for metconazole in 40 CFR §180.617(a)(1) 

should be stated according to HED’s Interim Guidance on Tolerance Expression (5/27/09, S. 

Knizer) as follows:

Tolerances are established for residues of metconazole, including its metabolites and 

degradates, in or on the commodities in the table below. Compliance with the tolerance 

levels specified below is to be determined by measuring only metconazole [5-[(4-

chlorophenyl)methyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)cyclopentanol] as the 

sum of its cis- and trans-isomers.

Adequate crop field trial data reflecting the proposed use patterns were submitted for purposes of 

establishing tolerances on the tuberous and corm vegetables subgroup 1C and the bushberry 

subgroup 13-07B. The tolerance spreadsheet in the Agency’s Guidance for Setting Pesticide 

Tolerances Based on Field Trial Data was utilized in determining the appropriate tolerance level 

for bushberries. The tolerance spreadsheet was not used to calculate the tolerance for tuberous 

and corm vegetables because residues in potatoes were below the LOQ (<0.04 ppm). The 

proposed tolerance of 0.02 ppm for tuberous and corm vegetables is too low. The tolerance 

should be established at 0.04 ppm, reflecting the combined LOQs of the metconazole 

enforcement method of 0.02 ppm for each of the cis- and trans- isomers of metconazole. The 

proposed tolerance of 0.35 ppm for bushberries is also too low; a tolerance must be proposed at 

0.40 ppm. 
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Based on the results of the potato processing study, in which residues of metconazole were 

<LOQ in potatoes following application at ≥5X the maximum proposed seasonal rate, tolerances 

for the processed commodities of potato are not needed.

The proposed and recommended tolerances for metconazole as a result of the subject action are 

presented in Table 1. The proposed tolerances should be revised to reflect the approved 

tolerance definition specified above, and the correct commodity definition and recommended 

tolerance levels as specified in Table 1.

Table 1. Tolerance Summary for Metconazole.

Commodity Proposed Tolerance

(ppm)

Recommended Tolerance

(ppm)

Comments

(correct commodity definition)

40 CFR §180.617(a)(2)

Tuberous and Corm 

Vegetable subgroup 1C

0.02 0.04 Vegetable, tuberous and corm, 

subgroup 1C

Bushberry subgroup 13-07B 0.35 0.40

2.3 Label Modifications

A revised Section B/label is requested. Since no spray adjuvants were used in the residue field 

trials on potatoes and blueberries, the Section B/label must be amended to include a statement 

that no adjuvant should be used for the tuberous and corm vegetable subgroup 1C and the 

bushberry subgroup 13-07B.

3.0 Ingredient Profile

3.1 Summary of Proposed Uses

IR-4 has submitted use directions under Section B of the petition which include the draft labeling 

for the 50 % WDG formulation of metconazole (V-10116 50 WDG, EPA Reg. No. 59639-147). 

IR-4 is proposing new foliar uses of metconazole on bushberries (crop subgroup 13-07B) and 

tuberous and corm vegetables (crop subgroup 1C). A summary of the proposed use directions 

for the intended crops is presented in Table 2. 
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Table 2. Summary of Directions for Use of Metconazole.

Applic. Timing, 

Type, and 

Equip.1

Formulation

[EPA Reg. 

No.]

Applic.Rate

oz/A

(lb ai/A)

Max. No. 

Applic. per 

Season

Max. 

Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

Tuberous and Corm Vegetables (Subgroup 1C): arracacha; arrowroot; artichoke, Chinese; artichoke, 

Jerusalem; canna (edible); cassava (bitter and sweet); chayote (root); chufa; dasheen (taro); ginger; leren; 

potato; sweet potato; tanier; turmeric; yam bean; yam true

Foliar,

Broadcast,

Ground (min. 10 

GPA2) or aerial 

(min. 5 GPA)

50% WG

[59639-147]

2.5 - 4.04

(0.078-

0.125)

4 

(Maximum 

of 2 

sequential 

applications)

16

(0.500) 1

Use as part of an 

Integrated Pest 

Management (IPM) 

program3. 

Apply when conditions 

favor disease 

development, prior to 

infection. Continue 

applications on a 7- to 14-

day retreatment interval. 

Do not apply more than 4 

applications per season. 

Do not make more than 2 

sequential applications.

Do not apply more than 

16 oz/A (0.500 lb ai/A) 

/season.

Bushberries (Subgroup 13-07B): aronia berry; blueberry, highbush; blueberry, lowbush; buffalo currant; 

Chilean guava; cranberry, highbush; currant, black; currant, red; elderberry; European barberry; 

gooseberry; honeysuckle (edible); huckleberry; jostaberry; juneberry (Saskatoon berry); lingonberry; 

native currant; salal; sea buckthorn; cultivars, varieties and/or hybrids of these.

Foliar,

Broadcast,

Ground (min. 20 

GPA) or aerial 

(min. 10 GPA)

50% WG

[59639-147]

2.5

(0.078)

3

(Maximum

of 2 

sequential 

applications)

0.234 7

Apply when conditions 

favor disease 

development, prior to 

infection, in sufficient 

water to obtain thorough 

coverage of blossoms, 

foliage, and/or fruit. 

Continue applications on 

a 7 to 14-day retreatment 

interval. Do not apply 

more than 3 applications 

per season.

1

 Do not apply through any type of irrigation system.

2

 Gallons per acre.

3 Apply in a regularly scheduled spray program in combination and/or rotation with other effective fungicides that 

have different modes of action (i.e., non Group 3 fungicides). Avoid rotating with other sterol biosynthesis 

inhibitors, such as Folicur®, Nova®, Procure® or Tilt®.

4

 For the control of white mold (Sclerotinia sclerotiorum), use 4 oz /A (0.125 lb ai/A) per application. Make first 

application prior to infection, generally at row closure and/or first bloom and the second application 14 days later 

if conditions favor white mold development.

Since no spray adjuvants were used in the residue field trials on potatoes and bushberries, the 

―Crop Specific Directions/Restrictions and Limitations‖ on the 50% WDG label for Bushberry,
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Subgroup 13-07 B and for Vegetable, Tuberous and Corm, Subgroup 1C must state that no spray 

adjuvant should be used for these crops.

3.2 Structure and Nomenclature

Structure and nomenclature are reported in Appendix C.

3.3 Physical and Chemical Properties

The physicochemical properties of metconazole are reported in Appendix C. 

4.0 Hazard Characterization/Assessment

4.1 Hazard and Dose-Response Characterization

4.1.1 Database Summary

The toxicological database for metconazole is adequate for the purpose of this risk assessment.

Two recent risk assessment documents (B. O’Keefe, 09/06/07, DP328676 and Y. Donovan, 

03/12/08, DP331937) contain detailed and up-to-date discussions of the toxicology and hazard 

evaluation of metconazole. Please refer to these documents for further extensive details. Also, 

please refer to Appendix 2 of this current risk assessment document for the toxicity profile 

tables.

Acute oral and dermal toxicities are category III, while acute inhalation is category IV. 

Metconazole is a moderate eye irritant (Category III) and a mild skin irritant (Category IV). It is 

not a skin sensitizer. The liver is the primary target organ in the mouse, rat and dog following 

oral exposure to metconazole via subchronic or chronic exposure durations. Developmental 

studies in rats and rabbits show some evidence of developmental effects, but only at dose levels 

that are maternally toxic. In the rat study, there is only low concern for the qualitative 

susceptibility (skeletal variation). Therefore, there is no residual uncertainty for pre- and/or postnatal toxicity. Metconazole did not demonstrate the potential for neurotoxicity in the four 

species (mouse, rat, dog and rabbit) tested. Metconazole is ―Not likely to be Carcinogenic to 

Humans‖ based on convincing evidence that carcinogenic effects are not likely below a defined 

dose that doesn’t cause mitogenesis.

4.1.2 Studies Available and Considered

The following data are available:

Acute- Oral rat, dermal rat, inhalation rat, eye irritation rabbit, dermal irritation rabbit, and skin 

sensitization guinea pig.

Subchronic- Oral 28-day rat; oral 90-day rat, oral 90-day mouse, oral 90-day dog;

Chronic- Oral rat and dog;

Reproductive/developmental- Oral developmental rabbit and rat; 2-generation reproductive rat

Other- Oral rat and mouse cancer studies, 21-day dermal toxicity and dermal penetration studies, 

subchronic neurotoxicity, mutagenicity screens and mechanistic studies.
Page 15 of 53

4.1.3 Sufficiency of Studies/Data

The toxicity database for metconazole is adequate for the purpose of this risk assessment (see 

Appendix A for Toxicity Profile tables). However, in accordance with the revised 40 CFR Part 

158 data requirements, an immunotoxicity study and a neurotoxicity battery are required. The 

existing database includes a recently submitted and reviewed immunotoxicity study, and a 

subchronic neurotoxicity study, but not an acute neurotoxicity study, and this remains a data 

deficiency. 

4.1.4 Toxicological Effects

Metconazole is a member of the triazole class of systemic fungicides and acts primarily as an 

inhibitor of ergosterol biosynthesis. The proposed mode of action for metconazole is via 

inhibition of sterol (ergosterol) biosynthesis in fungi which is consistent with altered cholesterol 

levels observed in mice and rats. 

Overall, metconazole appears to affect the liver, kidney, spleen, and certain blood parameters in 

all the species tested. Dose levels at which these effects occur are similar across species with the 

rat and dog being slightly more sensitive than the mouse. Like other triazoles, a primary target 

organ in mammalian toxicity studies is the liver. Liver toxicity was seen in the mouse, rat and 

dog following oral exposure to metconazole via subchronic or chronic exposure durations. 

While liver effects have been reported consistently across multiple durations and species, these 

effects were considered slight and minimal in some studies and appearing to be "adaptive" 

responses, but based on the weight of evidence from the consistency of these reported effects and 

evidence that these effects increase in severity with duration, and leading to liver tumors in the 

chronic mouse study, they were considered "adverse" and formed the basis of the study 

LOAELs. Metconazole is considered nongenotoxic and the liver tumors appear to have been 

formed via a mitogenic mode of action and therefore, metconazole is classified as "not likely to 

be carcinogenic to humans" at levels that do not cause mitogenesis. The established chronic RfD 

would be protective of mitogenesis/carcinogenesis.

Other major critical effects observed in oral studies were decreased body weight, decreased body 

weight gains, and blood effects (reductions in erythrocyte and/or platelet parameters) in the 

mouse, rat, dog and/or rabbit. Splenic effects including increased spleen weight and hyperplasia 

were observed in the mouse, rat and dog at dose levels where liver effects were also observed. 

However, a recently submitted and reviewed immunotoxicity study produced no evidence of 

immunotoxic potential at dose levels that produced systemic toxicity in rats. In dogs, lenticular 

degeneration (cataracts) was observed at the highest dose tested. Furthermore, at high dietary 

levels, there is evidence that metconazole is a gastrointestinal irritant in the dog. 

Developmental studies in rats and rabbits show some evidence of developmental effects, but only 

at dose levels that are maternally toxic. There was no quantitative susceptibility to the fetuses of 

rats or rabbits following in utero exposure to metconazole. In the developmental toxicity study 

in rats, skeletal variations (predominantly lumbar ribs) occurred in the presence of maternal 

toxicity (decreased body weight gains). In the prenatal developmental toxicity study in rabbits, 
Page 16 of 53

developmental effects (increased post-implantation loss and reduced fetal body weights) were 

observed at the same dose that caused maternal toxicity (decreased body weight gains, reduced 

food consumption and alterations in hematology parameters). In the two-generation 

reproduction study in rats, offspring toxicity (reduced fetal body weights F2 offspring and 

decreased viability in F1 and F2 offspring) was observed only at the highest tested dose, a dose 

which also resulted in parental toxicity as evidenced by reduced parental body weight and body 

weight gains, increased incidence of fatty hepatocyte changes in male parental animals and 

increased incidence of spleen congestion in F1 parental females. In the rat study, there is low 

concern for qualitative susceptibility (skeletal variation in the presence of minimal maternal 

toxicity) due to the presence of more severe effects at higher dose levels such as postimplantation loss, hydrocephaly and visceral anomalies. However, there is a clear NOAEL for 

these effects and the point of departure for this endpoint is based on skeletal variations. 

Therefore, it is concluded that there is no residual uncertainty for pre- and/or post-natal toxicity. 

Metconazole did not demonstrate neurotoxicity in the subchronic neurotoxicity study or the other 

submitted studies including acute, subchronic and chronic studies in several species, 

developmental toxicity studies in the rat and rabbit and a two generation reproduction study in 

the rat. No effects were noted on brain weights and no clinical signs possibly related to 

neurotoxicity were noted up to and including the high doses in all studies. However, In 

accordance with the revised 40 CFR Part 158 data requirements, an acute neurotoxicity study is 

required. The existing database does not include an acute neurotoxicity study, and this remains a 

data deficiency. 

Acute oral and dermal toxicities are category III, while acute inhalation is category IV. 

Metconazole is a moderate eye irritant (Category III) and a mild skin irritant (Category IV). It is 

not a skin sensitizer. 

4.1.5 Cancer Classification

Cancer Assessment Review Committee (CARC) Classification: ―Not Likely to be Carcinogenic 

to Humans‖ based on convincing evidence that a non-genotoxic mode of action for liver tumors 

was established in the mouse and that the carcinogenic effects were not likely below a defined 

dose that doesn’t cause mitogenesis based on bioassays in the rat and the mouse, combined with 

a lack of in vitro or in vivo mutagenicity (memo, J. Kidwell, TXR# 0054211, 4/14/06). No 

quantification required.

4.2 Absorption, Distribution, Metabolism, Excretion (ADME)

The absorption, distribution, metabolism and excretion (ADME) of metconazole was 

investigated in rats following single oral doses of cis and or cis/trans metconazole radiolabeled at 

the cyclopentyl or triazole ring (cis only). Initial studies showed less than 2% of the cyclopentyllabeled dose was expired in the air. Following a single oral administration of low dose (2 mg/kg) 

14C-cyclopentyl (cis/trans metconazole), greater than 80% of the administered dose was excreted 

in 24 hours with total excretion exceeding 90% in three days. Excretion was primarily via feces 

(80% male, 67% female) with biliary excretion being the prominent route of elimination. At 72 

hours, 15% and 26% of the radioactivity was excreted via urine in males and females, 
Page 17 of 53

respectively. A delay in excretion was observed following the administration of high dose (164 

mg/kg) 14C-cyclopentyl (cis/trans metconazole); however by 72 hours, 80% or more of the 

radioactivity was excreted. Males excreted lower amounts of radioactivity in the urine and 

greater amounts of radioactivity in the feces than females at low and high dose. Plasma 

pharmacokinetic studies showed a low potential for bioaccumulation following single or multiple 

dosing regimen. The time to maximum plasma concentration for male and female rats treated 

with either 2 mg/kg or 200 mg/kg was at the earliest sampling intervals of 0.25 hours and 4 

hours, respectively. The plasma half-life of low- and high-dose rats was slightly shorter in males 

than females, ~20-25 hours and ~34 hours, respectively.

Radioactivity measurements of tissues showed higher concentrations in the gastrointestinal tract, 

adrenals and liver. The pattern of metabolites was similar at the low and high dose. Analysis of 

fecal and urine samples showed little or no parent compound with ten key metabolites 

representing over 50% of the administered dose. Metconazole metabolites consist primarily of 

mono- and poly-hydroxylated derivatives of the parent molecule. Hydroxylation occurs mainly 

on the alkyl constituents of the phenyl and cyclopentyl rings. Sulfate conjugation to the 

cyclopentyl ring hydroxyl groups was also identified. Monohydroxy metabolites were found in 

the feces and di- and tri- hydroxy compounds were found more often in the urine. 

Administration of 200 mg/kg radiolabeled cis metconazole (14C-triazole ring) showed 

approximately 5% of the administered dose excreted as free triazole. 

4.3 FQPA Considerations

The toxicology database used to assess pre- and post-natal exposure to metconazole is 

considered adequate. 

4.4 FQPA Safety Factor for Infants and Children

The metconazole risk assessment team evaluated the quality of the toxicity and exposure data 

and, based on these data, recommended that the FQPA Safety Factor be reduced to 1X. The 

recommendation is based on the following:

The toxicology database for metconazole is complete for purposes of this risk assessment 

and the characterization of potential pre-natal and/or post-natal risks to infants and 

children.

There is no evidence of susceptibility following in utero exposure in the rabbit. In the rat 

there is qualitative evidence of susceptibility, however the concern is low since the 

developmental effects are characterized as variations (not malformations), occur in the 

presence of maternal toxicity, the NOAELs are well defined, and the dose/endpoint is 

used for acute dietary risk assessment for the sensitive population. There is no evidence 

of increased susceptibility in the offspring based on the result of the two-generation 

reproduction study.

In accordance with the revised 40 CFR Part 158 data requirements, a neurotoxicity 

battery is required for this risk assessment. The existing database does not include an 

acute neurotoxicity study, and this remains a data deficiency. However, an acceptable 
Page 18 of 53

subchronic neurotoxicity study showed no neurotoxic effects at levels that produced 

systemic toxicity in the study, as well as in other subchronic and chronic studies. 

Therefore, concern for potential neurotoxicity is low and the 10X FQPA factor is not 

retained. 

There is no evidence of increased susceptibility in the offspring based on the result of the 

two-generation reproduction study.

Dietary exposure assessments were conducted using tolerance level residues and assumed 

100% crop treated. Therefore, the acute and chronic dietary, food only, exposure is 

considered an upper bound conservative estimate. The contribution from drinking water 

is minimal. HED concludes that the acute and chronic exposure estimates in this analysis 

are unlikely to underestimate actual exposure. The drinking water component of the 

dietary assessment utilizes water concentration values generated by model and associated 

modeling parameters which are designed to provide conservative, health protective, highend estimates of water concentrations which will not likely be exceeded. While there is 

potential for post-application residential exposure, the best data and approaches currently 

available were used in the metconazole residential assessment. The Agency used the 

current conservative approaches for residential assessment, many of which include recent 

upgrades to the SOPs. The Agency believes that the calculated risks represent 

conservative estimates of exposure because maximum application rates are used to define 

residue levels upon which the calculations are based. Exposures are unlikely to be under 

estimated.

4.5 Hazard Identification and Toxicity Endpoint Selection

Hazard identification and toxicity endpoint selection were made for two different population 

subgroups: (1) Females 13-49 years of age, and (2) General Population including infants and 

children. Doses and endpoints were also selected for exposure routes (i.e., oral, dermal and 

inhalation) depending upon the appropriateness of the endpoint and the relevancy of the 

endpoints to the population of concern. Developmental (in utero exposure) endpoints were 

selected to assess dietary risks for Females 13-49 years of age, whereas non-developmental 

(systemic toxicity) endpoints were selected to assess dietary and non-occupational (residential) 

risks to the general population, including children and infants.

A summary of toxicological endpoints for use in human health risk assessment is presented 

below:
Page 19 of 53

Table 4. Summary of Toxicological Doses and Endpoints for Metconazole for Use in Dietary and NonOccupational Human Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty/FQPA 

Safety Factors

RfD, PAD, Level 

of Concern for 

Risk Assessment

Study and Toxicological Effects

Acute Dietary 

(General 

Population, 

including 

Infants and 

Children)

An appropriate dose/endpoint attributable to a single dose was not observed in the available oral 

toxicity studies reviewed.

Acute Dietary

(Females 13-49 

years of age)

NOAEL= 12 

mg/kg/day

UFA= 10X

UFH= 10X

FQPA SF= 1X

Acute RfD = 0.12 

mg/kg/day

aPAD= 0.12 

mg/kg/day

Developmental toxicity in rats:

LOAEL= 30 mg/kg/day based on 

increases in skeletal variations.

Chronic 

Dietary (All 

Populations)

NOAEL= 4.3 

mg/kg/day

UFA=10X

UFH= 10X

FQPA SF= 1X

Chronic RfD = 

0.04 mg/kg/day

cPAD = 0.04 

mg/kg/day

Chronic oral toxicity study in rats: 

LOAEL = 13.1 mg/kg/day based on 

increased liver (M) weights and 

associated hepatocellular lipid 

vacuolation (M) and centrilobular 

hypertrophy(M). Similar effects were 

observed in females at 54 mg/kg/day, 

plus increased spleen weight.

Incidental Oral 

Short-Term (1-

30 days)

NOAEL= 9.1 

mg/kg/day

UFA= 10X

UFH=10X

FQPA SF= 1X

Residential LOC 

for MOE = 100

28-Day oral toxicity study in rats:

LOAEL = 90.5 mg/kg/day based on 

decreased body weight (M), increased 

liver and kidney weight and 

hepatocellular hypertrophy and 

vacuolation (M/F).

Incidental Oral 

IntermediateTerm (1-6 

months)

NOAEL= 6.4 

mg/kg/day

UFA= 10X

UFH=10X

FQPA SF= 1X

Residential LOC 

for MOE = 100

90-Day oral toxicity study in rats:

LOAEL = 19.2 based on increased 

spleen wt (F) and hepatic vacuolation 

(M).

Dermal ShortTerm (1-30 

days)

Quantification of dermal risk is not required due to lack of systemic or dermal toxicity at the Limit 

Dose in a 21-day dermal toxicity study in the rat and the lack of target organ toxicity, neurotoxicity, 

developmental or reproductive toxicity.

Dermal 

IntermediateTerm (1-6 

months)

Inhalation 

Short- Term 

(1-30 days)

NOAEL= 9.1 

mg/kg/day

UFA= 10X

UFH=10X

FQPA SF= 1X

Residential LOC 

for MOE = 100

28-Day oral toxicity study in rats:

LOAEL = 90.5 mg/kg/day based on 

decreased body weight (M), increased 

liver and kidney weight and 

hepatocellular hypertrophy and 

vacuolation (M/F).

Inhalation 

IntermediateTerm (1-6 

months)

NOAEL= 6.4 

mg/kg/day

UFA= 10X

UFH=10X

FQPA SF= 1X

Residential LOC 

for MOE = 100

90-Day oral toxicity study in rats:

LOAEL = 19.2 mg/kg/day based on 

increased spleen wt (F) and hepatic 

vacuolation (M).

Cancer (oral, 

dermal, 

inhalation)

Classification: ―Not likely to be Carcinogenic to Humans‖
Page 20 of 53

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and used to mark the beginning 

of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. 

LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = 

potential variation in sensitivity among members of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = 

use of a short-term study for long-term risk assessment. UFDB = to account for the absence of key date (i.e., lack of a critical study). FQPA SF = 

FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level 

of concern. N/A = not applicable.

A summary of toxicological doses and endpoints for metconazole for use in occupational human 

health risk assessments is presented below:

Table 5. Summary of Toxicological Doses and Endpoints for Metconazole for Use in Occupational Human 

Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty 

Factors

Level of Concern for 

Risk Assessment

Study and Toxicological Effects

Dermal 

Short- (1-30 

days) & 

IntermediateTerm (1-6 

months)

Quantification of dermal risk is not required due to lack of systemic or dermal toxicity at the Limit 

Dose in a 21-day dermal toxicity study in the rat and the lack of target organ toxicity, neurotoxicity, 

developmental or reproductive toxicity.

Inhalation 

Short-Term 

(1-30 days)

NOAEL=9.1 

mg/kg/day

UFA=10X

UFH=10X

Occupational LOC for 

MOE = 100

28-Day oral toxicity study in rats:

LOAEL = 90.5 mg/kg/day based on 

decreased body weight (M), increased 

liver and kidney weight and 

hepatocellular hypertrophy and 

vacuolation (M/F).

Inhalation 

Intermediateterm (1-6 

months)

NOAEL=6.4 

mg/kg/day

UFA=10X

UFH=10X

Occupational LOC for 

MOE = 100

90-Day oral toxicity study in rats:

LOAEL = 19.2 mg/kg/day based on 

increased spleen wt (F) and hepatic 

vacuolation (M).

Cancer (oral, 

dermal, 

inhalation)

Classification: ―Not Likely to be Carcinogenic to Humans‖

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and used to mark the beginning 

of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. 

LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = 

potential variation in sensitivity among members of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = 

use of a short-term study for long-term risk assessment. UFDB = to account for the absence of key date (i.e., lack of a critical study). MOE = 

margin of exposure. LOC = level of concern. N/A = not applicable.

Based on the available toxicity database and the Agency's current practices, the inhalation risk 

for metconazole was assessed using an oral toxicity study. The Agency sought expert advice and 

input on issues related to this route to route extrapolation approach (i.e. the use of oral toxicity 

studies for inhalation risk assessment) from its Federal Insecticide, Fungicide, and Rodenticide 

Act Scientific Advisory Panel (SAP) in December 2009. The Agency received the SAP’s final 

report on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). 

The Agency is in the process of evaluating the SAP report and may, as appropriate, reexamine 

and develop new policies and procedures for conducting inhalation risk assessments, including 

route to route extrapolation of toxicity data. If any new policies or procedures are developed, the 

Agency may revisit the need for an inhalation toxicity study for metconazole and/or a 

reexamination of the inhalation toxicity risk assessment.
Page 21 of 53

4.5.1 Recommendation for combining routes of exposure for risk assessment

For short- and intermediate-term risk assessments, the oral and inhalation routes can be 

combined due to the common endpoint (liver toxicity) via the oral and inhalation (oral 

equivalent) routes. Quantification of dermal risk is not required. There are no potential longterm dermal or inhalation exposures to metconazole.

4.6 Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its most recent registration decision, EPA reviewed these data and 

selected the most sensitive endpoints for relevant risk assessment scenarios from the existing 

hazard database. However, as required by FFDCA section 408(p), Metconazole is subject to the 

endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a ―naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.‖ The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Metconazole is 

not among the group of 58 pesticide active ingredients on the initial list to be screened under the 

EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data callins, requiring the submission of EDSP screening assays for metconazole. For further 

information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, 

future lists, the test guidelines and the Tier 1 screening battery, please visit our website: 

http://www.epa.gov/endo/.
Page 22 of 53

5.0 Dietary Exposure/Risk Characterization

Reference: Metconazole. Petition for Registration of Use on Tuberous and Corm Vegetables Subgroup 1C and 

Bushberry Subgroup 13-07B (PP#0E7743). Summary of Analytical Chemistry and Residue Data. A. Acierto, 

DP380990, 3/24/11.

5.1 Pesticide Metabolism and Environmental Degradation

5.1.1 Metabolism in Primary Crops

No new metabolism data were submitted with the subject petition. Metabolism studies with 

banana, canola, mandarin, pea, and wheat were previously submitted. The metabolism of 

metconazole was found to be similar in all crops investigated. The main metabolic route of 

metconazole in crops is via oxidative hydroxylation of the methylene groups, the methyl groups 

on the cyclopentyl ring, and possibly the cyclopentyl ring. In addition, monohydroxylation may 

occur at the various pro-chiral carbons of metconazole, giving rise to chromatographically 

distinguishable stereoisomeric structures. The detection of TA and triazole conjugates in the 

canola, pea, and wheat studies indicates that the methylene group between the triazole and 

cyclopentyl rings is susceptible to oxidative hydroxylation. HED has determined that

metconazole (parent) is the residue of concern for both the tolerance expression and risk 

assessment purposes in plants except for cereal grains; the residues of concern for risk 

assessment in cereal grains are metconazole and the metabolite M11. For the purpose of the 

subject petition, the nature of the residue in plants is adequately understood.

5.1.2 Metabolism in Livestock

No new metabolism data were submitted with the subject petition. Adequate ruminant and 

poultry metabolism studies are available, and the data indicate that the metabolism of 

metconazole in ruminants and poultry is generally similar. The major routes of metabolism 

involve oxidation and/or oxidative hydroxylation of the methyl group at position 2 of the 

cyclopentyl ring and oxidative hydroxylation of the phenyl ring. Glucuronic acid conjugates 

were observed in the goat metabolism studies, and sulfate ester conjugates were observed in the 

hen metabolism study. In addition, in the hen metabolism study with triazole-labeled 

metconazole, C-N bond cleavage releasing 1,2,4-T was observed. Based on the available data, 

HED has determined that the residue of concern for the tolerance expression in livestock 

commodities is metconazole (parent). The residues of concern in livestock for purposes of the 

risk assessment are metconazole and metabolites M1 (free and conjugated), M12, and M31 (free 

and conjugated). For the purpose of the subject petition, the nature of the residue in livestock is 

adequately understood.
Page 23 of 53

5.1.3 Drinking Water Residue Profile

Reference: Drinking Water Exposure Assessment to Establish Tolerances of Parent Metconazole for 

Tuberous/Corm Vegetables (Subgroup 1C) and Bushberries (Subgroup 13-07B). DP375778 and DP380513, F.

Khan, 12/16/10.

A drinking water assessment for the proposed uses on the tuberous/corm vegetables and 

bushberries was performed using PRZM/EXAMS modeling. Estimated drinking water 

concentrations (EDWCs) of metconazole in drinking water from use on the existing and new 

crops were provided by EFED and incorporated directly into the acute and chronic dietary 

assessments. The EDWCs are based on the maximum proposed rates specified on the label. 

For surface water, the EDWCs for the proposed crops modeled in the assessment (highest of 

43.77 μg/L for cranberry scenario) did not exceed the acute EDWC of 45.48 μg/L for turf 

reported in a previous drinking water assessment (DP340378, 2007). Since the highest EDWC 

for the crops modeled in the current assessment is lower than the acute EDWC for turf reported 

in the previous drinking water assessment, EFED recommended the use of the previous EDWC. 

However, the annual mean (chronic) concentration of 38.16 μg/L for the cranberry scenario is 

higher than the previously reported highest EDWC (31.25 μg/L). Therefore, the 38.16 μg/L

value is recommended for the chronic non-cancer EDWC.

EFED calculated screening level ground water estimates for metconazole using the SCI-GROW

model. An acute and chronic ground water EDWC of 0.064 μg/L was estimated for the currently 

proposed uses. This EDWC is less than the 0.38 μg/L EDWC from non-agricultural uses 

generated from the maximum application rate for turf in a previous assessment (DP340378, 

2007).

Drinking Water Data for Free Triazoles

Residues of 1,2,4-triazole in drinking water were provided to HED by the Environmental Fate 

and Effects Division (I. Maher, DP320682, 28 Feb 2006). Due to the inter-conversion between 

1,2,4-triazole, triazole alanine, and triazole acetic acid that may occur in the environment, the 

residue estimates used in these assessments are a summation of all three residues and, therefore, 

represent an overestimate of actual concentrations of the common triazole metabolites in 

drinking water. The Tier II PRZM/EXAMS (surface water) and SCIGROW (ground water) 

residue estimates are summarized in Table 2. HED notes that there were no detects of 1,2,4-

triazole in any of the 271 water samples analyzed by PDP, with a limit of quantification of 730 

parts-per-trillion (0.73 ppb). The surface water estimates are significantly greater than those for 

ground water, and were used in the assessments for free triazole as well as the conjugated 

metabolites. The Environmental Fate and Effects Division stated in electronic communication 

(F. Khan, 4/7/2011) that the new metconazole uses are covered by the previous drinking water 

assessment for 1,2,4-triazole (DP320682, I. Maher, 2/28/06).

Table 6. Summary of Estimated Drinking Water Concentrations of 1,2,4-Triazole.

Exposure Duration Surface Water Concentration, ppm Groundwater Concentration, ppm

Acute 0.041 0.001

Chronic 0.011 0.001
Page 24 of 53

5.1.4 Food Residue Profile

Residues of Concern

Reference: Metconazole: FQPA Human Health Risk Assessment for Proposed New Uses on Small Grains, Stone 

Fruits, Tree Nuts, Peanuts, Soybeans, and Sugar Beets. PP#6F7094 and PP#6F7095. PC Code: 125619, DP331937 

and DP331926. Y. Donovan, 3/12/08.

A summary of the metabolites and degradates to be included in the risk assessment and tolerance 

expression are presented in Table 7 below. Detailed rationale for these conclusions were 

presented in a previous risk assessment document (DP Barcode 331926, Y Donovan, 03/12/08).

Table 7. Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance 

Expression.

Matrix Residues Included In Risk 

Assessment

Residues Included In 

Tolerance Expression

Plants Primary and Rotational 

Crops, except Cereal Grains

Metconazole Metconazole

Primary and Rotational 

Crops, Cereal Grains only

Metconazole and M11 Metconazole

Livestock

Metconazole; M1 and its 

glucuronic acid conjugate; M12; 

M31 and its glucuronic acid 

conjugate

Metconazole

Drinking Water Metconazole Not Applicable

Note: For all triazole-containing pesticides, the triazole-containing metabolites 1,2,4-T, TA, and TAA should also 

be included as residues of concern for risk assessment purposes only for plant and livestock commodities. Since 

these metabolites are common to the entire class of triazole-derivative fungicides and because of differential toxicity 

between the metabolites and the various parent compounds, risks associated with exposure to 1,2,4-T and to 

TA/TAA are addressed in separate risk assessment documents.

M1 = 5-[(4-chlorophenyl)methyl]-2-methoxyl-2-methyl-1-(1H-1,2,4-triazol-1-ylmethyl)-1-cyclopentanol; M11 = 5-

[(4-chlorophenyl)methoxyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)-1-cyclopentanol; M12 = 5-[(4-

chlorophenyl)methyl]-2-carboxyl-2-methyl-1-(1H-1,2,4-triazol-1-ylmethyl)-1-cyclopentanol; M31 = 

(1S*,3R*,5S*)-3-hydroxy-cis-metconazole; 1,2,4-T = 1H-1,2,4-triazole; TAA = 1H-1,2,4-triazol-1-yl acetic acid; 

TA = 2-amino-3-(1H-1,2,4-triazol-1-yl)propanoic acid.

Crop Field Trials

Potato

The IR-4, on behalf of the Agricultural Stations of Idaho, Michigan, North Dakota, North 

Carolina, and Oregon has submitted field trial data for metconazole on potatoes (MRID 

48143301). Pending review of the submitted triazole storage stability data, the submitted potato 

field trial data for metconazole are adequate to fulfill data requirements. The number and 

locations of field trials are in accordance with OPP Guideline 860.1500 for potato, the 
Page 25 of 53

representative crop for the tuberous and corm vegetable subgroup 1C, and the use pattern of the 

field trials adequately reflects the proposed use pattern for tuberous and corm vegetables. The 

available field trial data will support a tolerance of 0.04 ppm for tuberous and corm vegetables 

subgroup 1C, reflecting the combined LOQs of the enforcement method of 0.02 ppm for each of 

the cis- and trans-isomers of metconazole. 

Residues of 1,2,4-triazole and triazole acetic acid in potato tubers were each <0.02 ppm. In 9 of 

the 17 field trials, residues of triazole alanine in the treated samples were at 0.020-0.075 ppm 

(uncorrected for controls); residues in the control were 0.006-0.069 ppm. In the residue decline 

study, residues of triazole alanine were observed in one of two sites, although a clear pattern of 

decline could not be determined. The average triazole alanine residues (uncorrected for controls) 

over the 14-day period ranged from 0.022-0.027 ppm and 0.013 ppm in the corresponding 

control. 

The results of the potato field trials are summarized in Table 8.

Table 8. Summary of Residue Data from Potato Field Trials with a Metconazole Formulation (WDG).

Commodity Total 

Applic. Rate

(lb ai/A)

End-use 

Product

PHI2

(days)

Residue Levels (ppm)1

n Min. Max. HAFT2 Mean Std. Dev.

cis-Metconazole

Tuber 0.496-0.529 V-10116 

50 WDG 1-2 34 <0.020 <0.020 <0.020 <0.020 NA

trans-Metconazole

Tuber 0.496-0.529 V-10116 

50 WDG 1-2 34 <0.020 <0.020 <0.020 <0.020 NA

1,2,4-Triazole

Tuber 0.496-0.529 V-10116 

50 WDG 1-2 34 <0.020 <0.020 <0.020 <0.020 NA

Triazole Acetic Acid

Tuber 0.496-0.529 V-10116 

50 WDG 1-2 34 <0.020 <0.020 <0.020 <0.020 NA

Triazole Alanine

Tuber 0.496-0.529 V-10116 

50 WDG 1-2 34 <0.020 0.075 0.075 0.031 0.016

Total3

Tuber 0.496-0.529 V-10116 

50 WDG 1-2 34 <0.040 <0.040 <0.040 <0.040 NA

1 Residues of total metconazole calculated as the sum of the cis- and trans- isomers. The LOQ was 0.04 ppm for 

potato.

2 All studies had PHIs of 1 day except for one study with a PHI of 2 days.

3 Residues of total metconazole calculated as the sum of the cis- and trans- isomers. The LOQ was 0.04 ppm for 

potato.

Blueberry

The IR-4 submitted field trial data for metconazole residues in/on blueberry (MRID 48143302). 

Pending review of the submitted triazole storage stability data, the submitted blueberry field trial 

data for metconazole are adequate to fulfill data requirements. The number and locations of field 

trials are in accordance with the requirements of OCSPP Guideline 860.1500 for blueberry, the 
Page 26 of 53

representative crop of the bushberry subgroup 13-07B, and the use pattern of the field trials 

adequately reflects the proposed use pattern for bushberries. 

The available field trial data will support a tolerance of 0.40 ppm for the bushberry subgroup 13-

07B as calculated utilizing the tolerance spreadsheet in the Agency’s Guidance for Setting 

Pesticide Tolerances Based on Field Trial Data. 

Residues of the triazole metabolites were below the LOQ (<0.02 ppm) in/on all blueberry 

samples.

The results of the blueberry field trials are summarized in Table 9.

Table 9. Summary of Residue Data from Blueberry Field Trials with a Metconazole Formulation (WDG).

Commodity Total 

Applic. Rate

(lb ai/A)

End-use 

Product

PHI 

(days)

Residue Levels (ppm)1

n Min. Max. HAFT2 Mean3Std. Dev.

cis-Metconazole

Berries 0.240-0.265 V-10116 

50 WDG 6-8 22 <0.05 0.263 0.246 0.110 0.1

trans-Metconazole

Berries 0.240-0.265 V-10116 

50 WDG 6-8 22 <0.05 0.063 0.056 0.051 0.0

1,2,4-Triazole

Berries 0.240-0.265 V-10116 

50 WDG 6-8 22 <0.02 <0.02 <0.02 <0.02 NA

Triazole Acetic Acid

Berries 0.240-0.265 V-10116 

50 WDG 6-8 22 <0.02 <0.02 <0.02 <0.02 NA

Triazole Alanine

Berries 0.240-0.265 V-10116 

50 WDG 6-8 22 <0.02 <0.02 <0.02 <0.02 NA

Total4

Berries 0.240-0.265 V-10116 

50 WDG 6-8 22 <0.10 0.326 0.303 0.160 0.1

1 Residues less than the LOQ were considered to be the LOQ for calculations. The lowest level of method validation (LLMV) is 

0.05 ppm for isomers of metconazole and 0.02 ppm for metabolites. Residue levels include residues of metconazole and 

metabolites. No conversion factors were applied.

2 HAFT = highest average field trial.

3 Mean and standard deviations were calculated by the study author. Does not include additional sampling intervals collected for 

the residue decline study. 

4 Residues of total metconazole calculated as the sum of the cis- and trans- isomers. The LOQ was 0.04 ppm for blueberry.

Processed Food and Feed

Potato

IR-4 submitted a processing study for metconazole on potato (MRID 48143301). Residues were 

below the LOQ in/on potato tubers following application of the WDG formulation at an 

exaggerated rate of 2.5 or 3.1 lb ai/A (5x or 6.2x the proposed seasonal application rate). An 

acceptable method was used for quantitation of residues in potato tubers. The submitted potato 

processing study is acceptable to satisfy data requirements. Because residues of metconazole 

were below the LOQ in/on samples of potato treated with metconazole at ≥5X the maximum 
Page 27 of 53

proposed seasonal rate, analysis of processed samples is not required. HED concludes that 

quantifiable residues of metconazole in potato processed commodities are not expected, and 

separate tolerances are not needed. The residue data from the processing study is summarized in 

Table 10.
Page 28 of 53

Table 10. Residue Data from Potato Processing Study with Metconazole.

RAC Processed 

Commodity

Total Rate

(lb a.i./A) 

PHI 

(days)

Residues (ppm) Processing Factor1

cismetcon

azole

transmetcon

azole

T TAA TA TA 

corrected

Total 

metcon

azole

cismetcon

azole

transmetcon

azole

T TAA TA TA 

correct

ed

Total 

metcon

azole

Prosser, WA; 2007 (07-WA33)

Potato Tuber (RAC) 2.498 1 <0.020 <0.020 <0.020 <0.020 0.066 0.027 <0.040 -- -- -- -- -- -- --

Flakes NA NA NA NA NA NA NA NC NC NC NC NC NC NC

Chips NA NA NA NA NA NA NA NC NC NC NC NC NC NC

Wet peel NA NA NA NA NA NA NA NC NC NC NC NC NC NC

Weslaco, TX; 2007 (07-TX28)

Potato Tuber (RAC) 3.137 1 <0.020 <0.020 <0.020 <0.020 <0.020 -- <0.040 -- -- -- -- -- -- --

Flakes NA NA NA NA NA NA NA NC NC NC NC NC NC NC

Chips NA NA NA NA NA NA NA NC NC NC NC NC NC NC

Wet peel NA NA NA NA NA NA NA NC NC NC NC NC NC NC

NA = Not analyzed. The LOQ was 0.020 ppm for metconazole and metabolites.

1 NC = Not calculated; processed fractions were not analyzed.
Page 29 of 53

Meat, Milk, Poultry, and Eggs

No livestock feed items are associated with bushberries. The only livestock feedstuffs associated 

with this current petition (PP#0E7743) are processed potato waste and potato culls; these 

commodities are fed to beef and dairy cattle but are not fed to poultry or swine. The dietary 

burdens of metconazole to livestock, based on reasonably balanced diets, were calculated in a 

previous review (DP350367, N. Dodd, 9/18/08). Dietary burdens were 4.2 and 6.6 ppm for beef 

and dairy cattle, respectively, and 1.9 and 0.64 ppm for poultry and swine, respectively, and were 

calculated based on tolerances for cereal grain, sugarcane, cotton, and soybean commodities. 

Residues of metconazole from the submitted crop field studies were below the LOQ in/on 

potatoes following application at 5X the proposed maximum seasonal application rate; therefore, 

quantifiable residues of metconazole are not expected in potato processed commodities. 

Consequently, the addition of the use of metconazole on tuberous and corm vegetables is not 

expected to alter the dietary exposure of ruminants because residues of metconazole were 

nonquantifiable in potato treated at 1X and 5X the maximum proposed seasonal application rate. 

Therefore, no changes are required in the current livestock tolerances for metconazole.

Field Accumulation in Rotational Crops

No new field studies have been submitted. The earlier reviews required that end-use labels 

include plant-back restrictions of 30 days for leafy vegetables and Brassica leafy vegetables and 

120 days for all remaining crops other than those with labeled uses. This requirement has been 

fulfilled and the statement now appears in the master label.

5.2 Dietary Exposure and Risk

Reference: Metconazole: Acute and Chronic Dietary (Food and Drinking Water) Exposure and Risk Assessment 

for Residues in/on Vegetables, Tuberous & Corm, Subgroup 1C and Bushberry Subgroup 13-07B. A. Acierto, 

DP387504.drs, 3/28/11.

Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments 

were conducted using the Dietary Exposure Evaluation Model (DEEM-FCIDTM, Version 2.03), 

which uses food consumption data from the USDA’s Continuing Surveys of Food Intakes by 

Individuals (CSFII) from 1994-1996 and 1998. Conservative acute and chronic dietary exposure 

assessments were conducted for all existing and proposed food uses of metconazole and drinking 

water. Residues of the proposed food commodities were based on field trial data on the 

representative crops (potato and blueberry). The conservative assessment assumed that 

metconazole residues are present in all registered and proposed food commodities at tolerance 

levels and that 100% of the crops were treated. All processing factors for the proposed 

tuberous/corm vegetable commodities were set to 1, based on the results of processing studies 

demonstrating that residues of metconazole in potato processed commodities would not exceed 

the raw agricultural commodity (RAC) tolerance.
Page 30 of 53

5.2.1 Acute Dietary Exposure/Risk

The acute dietary exposure assessment was performed only for females 13-49 years old since an 

acute endpoint was not identified for the general U.S. population. Estimated acute dietary 

exposure to metconazole from food and drinking water is below HED’s level of concern. 

Combined dietary exposure from food and drinking water at the 95th percentile of exposure is 

estimated to be 0.004578 mg/kg/day for females13-49 years old, equivalent to 3.8% of the acute 

Population Adjusted Dose (aPAD); therefore, the exposure is not of concern to HED (i.e., 

<100% aPAD).

5.2.2 Chronic Dietary Exposure/Risk

Chronic dietary (food and drinking water) exposure estimates are well below HED’s level of 

concern. Using EDWCs from the cranberry crop scenario, chronic (food and drinking water) 

dietary exposure is estimated at 0.002434 mg/kg/day for the general U.S. population (6.1% of the 

chronic Population Adjusted Dose (cPAD)) and 0.005026 mg/kg/day (12.6% of the cPAD) for 

children 1-2 years old, the population subgroup with the highest estimated chronic dietary 

exposure to metconazole. 

Table 11. Summary of Dietary (Food and Drinking Water) Exposure Risk for Metconazolet1.

Population Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary

Dietary 

Exposure 

(mg/kg/day)

% aPAD

Dietary 

Exposure

(mg/kg/day)

% cPAD

General U.S. Population 0.002434 6

All Infants (<1 year old) 0.004831 12.1

Children 1-2 years old 0.005026 12.6

Children 3-5 years old 0..004800 12

Children 6-12 years old 0.003289 8.2

Youth 13-19 years old 0.001961 4.9

Adults 20-49 years old 0.002158 5.4

Adults 50+ years old 0.001868 4.7

Females 13-49 years old 0.004578 3.8 0.001874 4.7

1 The values for the highest exposed population for each type of risk assessment are bolded.

5.3 Anticipated Residue and Percent Crop Treated (%CT) Information

The acute and chronic dietary (food and drinking water) exposure and risk estimates are 

conservative since they assume that 100% of crops are treated with metconazole and that the 

residues are present at tolerance levels. In addition, drinking water exposure estimates were 
Page 31 of 53

based on screening level estimates generated by the PRIZM-EXAMS model. Although not 

needed at this time, HED could refine the exposure and risk estimates through the use of 

anticipated residues and percent crop treated data as well as refined estimated drinking water 

concentrations. However, since estimated exposures and risks using conservative assumptions 

are well below HED’s level of concern, such refinement is not warranted.

5.4 Dietary Assessment of Free Triazole and its Conjugates

Reference: Common Triazole Metabolites: Updated Dietary (Food + Water) Exposure and Risk Assessment to 

Address The Amended Metconazole Section 3 Registration to Add Uses on Tuberous and Corm Vegetables (Group 

1C) and Bushberry Subgroup 13-07B. T. Morton, DP388469.drs, 4/27/11.

Since metconazole is a triazole, a separate updated dietary exposure and risk analysis 

(DP388469.drs, T. Morton, 4/27/11) for the common triazole metabolites 1,2,4-triazole (T), 

triazolylalanine (TA), triazolylacetic acid (TAA), and triazolylpyruvic acid (TP) was conducted. 

The updated assessment addressed requested new uses of metconazole on tuberous and corm 

vegetables and bushberries.

Four assessments were conducted: acute and chronic durations for T, and acute and chronic 

durations for combined residues of TA, and TAA. Residue chemistry databases for metconazole 

parent compound included residue measurements for the triazole metabolites in/or tuberous and 

corm vegetables (Group 1C) and bushberry subgroup 13-07B. As with the previous triazole 

metabolite assessments, this assessment includes exposure estimates resulting from direct 

consumption of T, TA, and TAA as well as indirect exposure resulting from consumption of 

parent fungicides followed by in vivo conversion to the metabolites. For each food form in the 

acute assessment, the residue used is the maximum estimate from the various food/triazole 

fungicide combinations combined with the average indirect residue estimate. For the chronic 

assessments, the residue estimates are the average residue from the food-specific food/triazole 

combinations combined with the average indirect residue estimates. All four assessments 

assume 100% crop treated and include conservative estimates for residues of the metabolites in 

drinking water. The resulting exposure and risk estimates are based on health-protective 

assumptions and should be characterized as conservative.

For all four analyses, risk estimates are below HED’s level of concern for all population 

subgroups. There are no dietary exposure considerations for the common triazole metabolites 

that would preclude granting the registration requests for metconazole. 
Page 32 of 53

Table 12. Summary of Dietary (Food and Drinking Water) Exposure and Risk for the Common Triazole 

Metabolites Adding the New Section 3 Uses for Metconazole.

Population Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary Cancer

Dietary 

Exposure 

(mg/kg/day)

% aPAD*

Dietary 

Exposure

(mg/kg/day)

% cPAD*

Dietary 

Exposure

(mg/kg/day)

Risk

1,2,4-Triazole

General U.S. Population 0.006383 21 0.001191 24

Not 

Applicable

Not 

Applicable

All Infants (< 1 year old) 0.011430 38 0.001879 38

Children 1-2 years old 0.014129 47 0.002944 59

Children 3-5 years old 0.011683 39 0.002472 49

Children 6-12 years old 0.007713 26 0.001609 32

Youth 13-19 years old 0.005402 18 0.001028 21

Adults 20-49 years old 0.005101 17 0.001004 20

Adults 50+ years old 0.004639 15 0.000925 19

Females 13-49 years old 0.004898 16 0.000993 20

Triazolylalanine + Triazolylacetic Acid 

General U.S. Population

Not 

Applicable

Not 

Applicable

0.014081 16

Not 

Applicable

Not 

Applicable

All Infants (< 1 year old) 0.018206 20

Children 1-2 years old 0.038106 42

Children 3-5 years old 0.030642 34

Children 6-12 years old 0.019145 21

Youth 13-19 years old 0.012441 14

Adults 20-49 years old 0.011755 13

Adults 50+ years old 0.010510 12

Females 13-49 years old 0.052303 52 0.011548 13

* The values for the highest exposed population for each type of risk assessment are bolded.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

No new residential uses are being requested at this time. However, adults, adolescents, and 

children may be exposed to metconazole from its currently registered uses on turf and 

ornamentals. These risks have been previously assessed (DP341832, J. Arthur, 8/3/07). Because 

dermal toxicity endpoints for the appropriate duration of exposure (short- and intermediate-term) 

were not identified up to the limit dose, only residential handler and postapplication inhalation 

exposures/risks for adults, and residential post-application incidental oral exposures/risks for 

children have been assessed. 

Spray drift is always a potential source of exposure to residents nearby to spraying operations. 

This is particularly the case with aerial application (a method proposed to be employed for 

metconazole), but, to a lesser extent, could also be a potential source of exposure from the 

ground application method also employed for metconazole. The Agency has been working with 

the Spray Drift Task Force, EPA Regional Offices, and State Lead Agencies for pesticide 

regulation and other parties to develop the best spray drift management practices. On a chemical 

by chemical basis, the Agency is now requiring interim mitigation measures for aerial 

applications that must be placed on product labels/labeling. The Agency has completed its 

evaluation of the new database submitted by the Spray Drift Task Force, a membership of U.S. 

pesticide registrants, and is developing a policy on how to appropriately apply the data and the 
Page 33 of 53

AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast,

and ground hydraulic methods. After the policy is in place, the Agency may impose further 

refinements in spray drift management practices to reduce off-target drift with specific products 

with significant risks associated with drift.

6.1 Residential Handler Exposure and Risk Characterization

Residential handler exposures are expected to be short-term in duration. An MOE 100 is 

adequate to protect residential pesticide handlers. All metconazole residential handler MOEs are 

estimated to be >100 for the established residential uses, and therefore, do not cause concern for 

HED. A summary of these exposures and risks is presented in Table 13.

Although a point of departue from an oral study was used to assess residential handler inhalation 

risks for metconazole, HED does not believe this assessment is under-protective of adult 

handlers. MOEs calculated for residential handlers were all > 71,000, thus providing an ample 

margin of safety to account for any uncertainties in route-to-route extrapolation. Short-term 

inhalation risks were not of concern to HED. 

Table 13. Residential Handler Short-term Inhalation Exposures and Risks.

Scenario Exposure 

Route

Max. Rate 

Application 

Unit 

Exposure

Amount 

Treated/Day

Daily Dose

(mg/kg/day)1

Inhalation 

MOE2

1) mixer/loader/applicator 

w/ hose-end sprayer 

(ornamentals)

Inhalation 0.0025 lb ai/ 

Gal.

0.017 

mg/lb ai 

100 Gal. 0.000061 150,000

2) mixer/loader/applicator 

w/ low-pressure handwand sprayer 

(ornamentals)

Inhalation 0.0025 lb ai/ 

Gal.

0.03 mg/lb 

ai

5 Gal. 0.0000054 1,700,000

3) mixer/loader/applicator 

w/ hose-end sprayer (turf)

Inhalation 0.6 lb ai/ 

Acre

0.017 

mg/lb ai

0.023 Acre = 

1000 ft2

0.0000034 2,700,000

4) mixer/loader/applicator 

w/ low-pressure handwand sprayer (turf)

Inhalation 0.6 lb ai/ 

Acre

0.03 mg/lb 

ai

0.5 Acre 0.00013 71,000

1. Daily Dose = Application Rate * Unit Exposure * Amount Treated * Absorption factor (100% for 

inhalation)/Body Weight (70 kg).

2. Inhalation MOE = Inhalation short-term NOAEL (9.1 mg/kg/day) ÷ Daily Dose 

6.2 Residential Post-Application Exposure and Risk Characterization

Adults, adolescents, and children may be exposed to metconazole from its proposed residential 

uses. Adults and adolescents may experience short- and intermediate-term dermal exposure 

from golfing and other activities on treated turf, as well as from tending treated ornamentals. 

Children age 3 to <6 years old may experience short- and intermediate-term dermal and 

incidental oral exposure from activities on treated turf. However, because dermal toxicity 

endpoints for the appropriate durations of exposure were not identified up to the limit dose, and 

because inhalation exposure is considered to be insignificant for post-application exposures, only 

toddler incidental oral post-application exposures have been assessed. 
Page 34 of 53

Residential Post-Application Exposure on Treated Lawns

Post-application risks to children following the application of metconazole to home lawns were 

calculated for short- and intermediate-term incidental oral exposures. A summary of the 

estimated exposures and risks, along with the algorithms used for each small child exposure 

scenario are presented below in Tables 14 through 16. All MOEs for toddler lawn exposure 

scenarios were >100 and, therefore, are not of concern to HED. In addition, the total MOEs for 

combined toddler exposures (i.e., short-term and intermediate-term hand-to-mouth, object-tomouth, and incidental ingestion of soil) are >100 (see Table 17), and therefore, do not concern 

HED.
Page 35 of 53

Table 14. Oral Hand-to-mouth Short- (ST) and Intermediate-term (IT) Exposures and Risks for Children from Treated Lawns

Application Rate (lb 

ai/A)

Fraction of ai 

Available

Turf Transferrable 

Residue at Day ―0" 

(μg/cm2)

1

Exposure 

Time 

(hrs/day)

Extraction 

by saliva

Hand Surface 

Area 

(cm2/event)

Frequency

(events/ hr)

Body Weight

(kg)

Daily Dose2

(mg/kg/day)

MOE3

0.6 0.05 0.34 2 0.5 20 20 (ST) 15 0.0091 (ST) 1000 (ST)

9.5 (IT) 0.0043 (IT) 1500 (IT)

1Turf Transferrable Residue (μg/cm2

) = Application rate (lb ai/A) x Fraction of ai Available x 4.54E+8 μg/lb x 2.47E-8 A/cm2

2 Daily Dose = (Turf Transferrable Residue x Extraction by Saliva x Hand Surface Area x Frequency x 1E-3 mg/ μg x Exposure Time) / (Body Weight)

3 MOE = Short-term Oral NOAEL (9.1 mg/kg/day) or Intermediate-Term Oral NOAEL (6.4 mg/kg/day) /Daily Dose.

Table 15. Oral Object-to-mouth (Turfgrass) Short- (ST) and Intermediate-term (IT) Exposures and Risks for Children from Treated Lawns

Application Rate (lb 

ai/A)

Fraction of ai 

Available

Grass Residue at Day ―0" (μg/cm2)

1

Surface Area Mouthed 

(cm2/day)

Body Weight

(kg)

Daily Dose2

(mg/kg/day)

MOE3

0.6 0.20 1.3 25 15 0.0022

4100 (ST)

2900 (IT)

1Grass Residue (μg/cm2

) = = Application rate (lb ai/A) x Fraction of ai Available x 4.54E+8 μg/lb x 2.47E-8 A/cm2

2 Daily Dose = [Grass residue (μg/cm2) x Surface Area Mouthed (cm2/day) x 1E-3 mg/μg] / [Body Weight (kg)]

3 MOE = Short-term Oral NOAEL (9.1 mg/kg/day) or Intermediate-Term Oral NOAEL (6.4 mg/kg/day) /Daily Dose 

Table 16. Short- (ST) and Intermediate-term (IT) Exposure and Risk for Children from Ingestion of Soil from Treated Lawns 

Application Rate (lb 

ai/A)

Fraction of ai 

Available

Soil Residue at Day ―0"

(μg/g)1

Ingestion Rate

(mg/day)

Body 

Weight (kg)

Daily Dose2

(mg/kg/day)

MOE3

0.6 1 4.51 100 15 0.00003 300,000 (ST)

210,000 (IT)

1 Soil residue (μg/g) = [Application Rate (lbs ai/A) x Fraction of ai Available x 4.54E+8 μg/lb x 2.47E-8 A/cm2

x 0.67 cm3/g soil]

2 Daily Dose = [Soil residue (μg/g) x Ingestion rate (mg/day) x 1E-6 g/μg] / [Body Weight (kg)]

3 MOE = Short-term Oral NOAEL (9.1 mg/kg/day) or Intermediate-Term Oral NOAEL (6.4 mg/kg/day) /Daily Dose
Page 36 of 53

Table 17. Children’s Residential Combined Short- and Intermediate-term Risk from Treated Turf

Route Daily Dose 

(mg/kg/day)

MOE Total ST MOE1 Total IT MOE2

Hand-to-Mouth 0.0091 (ST) 1000 (ST)

810 1000

0.0043 (IT) 1500 (IT)

Object-to-Mouth 0.0022 4100 (ST)

2900 (IT)

Soil Ingestion 0.00003 310,000 (ST)

220,000 (IT)

1. Total ST MOE = 1 ÷ [(1/ST Hand-to-Mouth MOE) + (1/ST Object-to-Mouth MOE) + (1/ST Soil Ingestion MOE)]

2. Total IT MOE = 1 ÷ [(1/IT Hand-to-Mouth MOE) + (1/IT Object-to-Mouth MOE) + (1/IT Soil Ingestion MOE)]

7.0 Aggregate Risk Assessments and Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risks from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure.

7.1 Acute & Chronic Aggregate Risk

Acute and chronic aggregate exposures include food plus drinking water exposures. As 

demonstrated under Section 5.2, acute and chronic aggregate risks are not of concern.

7.2 Short- and Intermediate-Term Aggregate Risk

The short- and intermediate-term aggregate risk assessments consider average (chronic) exposure 

estimates from dietary consumption of metconazole (food and drinking water) and nonoccupational/residential use on turf (dermal and inhalation exposures for adults, and dermal plus 

incidental oral exposures for children). 

For adults applying metconazole to turf, short- and intermediate-term exposures were 

aggregated. The exposure scenario with the highest daily dose and lowest MOE was used; i.e., 

mixer/loader/applicator with a low pressure handwand sprayer. 

The short-and intermediate-term aggregate MOEs from dietary exposure (food + drinking water)

and non-occupational/residential handler exposure (inhalation) for adults are 1,700 and 1,700, 

respectively; which are not of concern to HED (see Table 18 below), since they are greater than 

the level of concern MOE of 100. 
Page 37 of 53

Table 18. Short- and Intermediate-Term Aggregate Risk Calculations for Adult Handlers

Population/

Exposure 

Duration

Inhalation Exposure Dietary Exposure Short- or 

IntermediateTerm 

Aggregate 

MOE2

NOAEL 

(mg/kg/day)

Exposure 

(mg/kg/day)

MOE1 NOAEL 

(mg/kg/day)

Exposure 

(mg/kg/day)

MOE1

Adult ST 9.1 0.00013 70,000 4.3 0.002434 1,800 1,700 ST

Adult IT 6.4 0.00013 49,000 4.3 0.002434 1,800 1,700 ST

1 MOE = NOAEL / Exposure; The Level of Concern MOE is 100.

2 Aggregate MOE = 1/ [(1/MOEInhalation) + (1/MOEFood + Drinking Water)]

Post-application exposures from the use on turf are considered predominantly short-term (1-30 

days). Although exposures are expected via the dermal route, quantification of dermal risk is not 

required, since a dermal endpoint was not identified for short-, or intermediate-term exposures. 

Therefore, short- and intermediate-term post-application aggregate risk assessments were 

conducted only for average dietary and incidental oral exposures to toddlers. The short-and 

intermediate-term aggregate MOEs from dietary exposure (food + drinking water) and nonoccupational/residential exposure (incidental oral) for children 1-2 years old are 420 and 460, 

respectively; these MOEs are not of concern to HED (see Table 19 below), since they are greater 

than the level of concern MOE of 100. 

Table 19. Short-and Intermediate-Term Aggregate Risk Calculations for Postapplication Exposures

Population/ 

Exposure 

Duration

Incidental Oral Exposure Dietary Exposure Short-or 

IntermediateTerm 

Aggregate 

MOE2

NOAEL 

(mg/kg/day)

Exposure 

(mg/kg/day)

MOE1 NOAEL 

(mg/kg/day)

Exposure 

(mg/kg/day)

MOE1

Kids 1-2 yrs/ST 9.1 0.01123 810 4.3 0.005026 860 420 ST

Kids 1-2 yrs/IT 6.4 0.00643 1000 4.3 0.005026 860 460 IT

1 MOE = NOAEL / Exposure; The Level of Concern MOE is 100.

2 Aggregate MOE = 1/ [(1/MOEIncidental Oral) + (1/MOEFood + Drinking Water)]

These aggregate exposure assessments are considered conservative estimates, that should not 

underestimate risks, for the following reasons: 1) the dietary inputs used tolerance-level residues, 

100% crop treated, and crop specific (turf) screening level drinking water modeling data (i.e., 

surface water modeling); 2) maximum application rates and minimum application intervals were 

used; and 3) conservative SOPs and upper level estimates of exposure were employed.

Updated Aggregate Assessment of Free Triazole & its Conjugates

Reference: Common Triazole Metabolites: Updated Aggregate Human Health Risk Assessment to Address 

Tolerance Petitions for Metconazole. DP389080, T. Morton, 4/27/11.

In 2006, HED issued aggregate human health risk assessments for T and the conjugated triazole 

metabolites (DP322215, M. Doherty, et al., 2/7/06). Those assessments addressed a back-log of 

triazole use requests that had been held by the Agency pending resolution of various 

toxicological and exposure concerns for the common triazole metabolites. The findings of that 
Page 38 of 53

assessment were that risk estimates for all exposure scenarios were below HED’s level of 

concern. Since that time, a number of requests for new uses of triazole-derivative fungicides 

have been submitted to the Agency. As a result of these requests, new dietary exposure 

estimates have been made for T and combined residues of TA, TAA, and TP, and new aggregate 

exposure and risk estimates are necessary. Neither the toxicological information nor the nondietary exposure estimates detailed in the 2006 memorandum have changed; thus, the only 

alterations to the previous aggregate exposure and risk estimates are due to changes in the dietary 

exposure estimates. For complete hazard characterization and non-dietary exposure assessments 

for the common triazole metabolites, see the 2006 risk assessment.

The revised aggregate estimates are summarized below for short- and intermediate-term 

scenarios for T (Tables 20 and 21, respectively). The conjugated triazole metabolites are formed 

in plants by the conjugation of 1,2,4-T to serine. The TA may then be further metabolized to 

form TAA and/or TP. Because of the nature of this process, HED has assumed that it occurs 

within the plant itself and not on leaf surfaces. Therefore, the residues are not available for 

dermal, hand-to-mouth, or object-to-mouth exposures and HED has not conducted a residential 

exposure assessment for the triazole conjugates. Residues of TA, TAA, and TP may occur in 

soil. 1,2,4-Triazole is more toxic than TA/TAA/TP and exposures to these via soil ingestion are 

unlikely to exceed those of 1,2,4-T. The assessment for soil ingestion of 1,2,4-T shows that risk 

estimates are below HED’s level of concern; therefore, risk estimates for soil ingestion of the 

conjugates will also be below HED’s level of concern.

Table 20. Short-term Aggregate Exposure and Risk Estimates for 1,2,4-Triazole.

Population Subgroup

Exposure Estimate, mg/kg/day1

Aggregate 

MOE2 Dietary

Dermal

(M/L/A)

Dermal 

(PostApplic.)Hand-toMouthObjectto-MouthSoil 

Ingestion Aggregate

U.S. Population (total) 0.001191 0.00183 0.0051 N/A N/A N/A 0.008121 3700

All infants (< 1 year) 0.001879 N/A 0.0086 0.0041 0.0010 0.000019 0.015598 1900

Children 1-2 yrs 0.002944 N/A 0.0086 0.0041 0.0010 0.000019 0.016663 1800

Children 3-5 yrs 0.002472 N/A 0.0086 0.0041 0.0010 0.000019 0.016191 1900

Children 6-12 yrs 0.001609 N/A 0.0086 N/A N/A N/A 0.010209 2900

Youth 13-19 yrs 0.001028 0.00183 0.0051 N/A N/A N/A 0.007958 3800

Adults 20-49 yrs 0.001004 0.00183 0.0051 N/A N/A N/A 0.007934 3800

Adults 50+ yrs 0.000925 0.00183 0.0051 N/A N/A N/A 0.007855 3800

Females 13-49 yrs 0.000993 0.00183 0.0051 N/A N/A N/A 0.007923 3800

1 Exposure estimates for dermal, hand-to-mouth, object-to-mouth, and soil ingestion are from J. Arthur, DP 322240, 12/9/05.

2 Aggregate MOE = NOAEL (30 mg/kg/day) ÷ Aggregate Exposure Estimate (mg/kg/day). Level of Concern = 1000.

Table 21. Intermediate-term Aggregate Exposure and Risk Estimates for 1,2,4-Triazole.

Population Subgroup

Exposure Estimate, mg/kg/day

Aggregate MOE2 Dietary Soil Ingestion1 Aggregate

U.S. Population (total) 0.001191 N/A 0.001191 13000

All infants (< 1 year) 0.001879 0.000019 0.001898 7900

Children 1-2 yrs 0.002944 0.000019 0.002963 5100

Children 3-5 yrs 0.002472 0.000019 0.002491 6000

Children 6-12 yrs 0.001609 N/A 0.001609 9300

Youth 13-19 yrs 0.001028 N/A 0.001028 15000

Adults 20-49 yrs 0.001004 N/A 0.001004 15000

Adults 50+ yrs 0.000925 N/A 0.000925 16000

Females 13-49 yrs 0.000993 N/A 0.000993 15000

1 Soil ingestion estimates are from J. Arthur, DP 322240, 12/9/05

2 Aggregate MOE = NOAEL (15 mg/kg/day) ÷ Aggregate Exposure Estimate (mg/kg/day). Level of Concern = 3000.
Page 39 of 53

8.0 Cumulative Risk Characterization/Assessment

Metconazole is a member of the triazole-containing class of pesticides. Although conazoles act 

similarly in plants (fungi) by inhibiting ergosterol biosynthesis, there is not necessarily a 

relationship between their pesticidal activity and their mechanism of toxicity in mammals. 

Structural similarities do not constitute a common mechanism of toxicity. Evidence is needed to 

establish that the chemicals operate by the same, or essentially the same, sequence of major 

biochemical events (EPA, 2002). In conazoles, however, a variable pattern of toxicological 

responses is found; some are hepatotoxic and hepatocarcinogenic in mice. Some induce thyroid 

tumors in rats. Some induce developmental, reproductive, and neurological effects in rodents. 

Furthermore, the conazoles produce a diverse range of biochemical events including altered 

cholesterol levels, stress responses, and altered DNA methylation. It is not clearly understood 

whether these biochemical events are directly connected to their toxicological outcomes. Thus, 

there is currently no evidence to indicate that conazoles share common mechanisms of toxicity 

and EPA is not following a cumulative risk approach based on a common mechanism of toxicity 

for the conazoles. For information regarding EPA’s procedures for cumulating effects from 

substances found to have a common mechanism of toxicity, see EPA’s website at 

http://www.epa.gov/pesticides/cumulative.

Metconazole is a triazole-derived pesticide. This class of compounds can form the common 

metabolite 1,2,4-triazole and two triazole conjugates (triazolylalanine and triazolylacetic acid). 

To support existing tolerances and to establish new tolerances for triazole-derivative pesticides, 

including metconazole, U.S. EPA conducted a human health risk assessment for exposure to 

1,2,4-triazole, triazolylalanine, and triazolylacetic acid resulting from the use of all current and 

pending uses of any triazole-derived fungicide. The risk assessment is a highly conservative, 

screening-level evaluation in terms of hazards associated with common metabolites (e.g., use of 

a maximum combination of uncertainty factors) and potential dietary and non-dietary exposures 

(i.e., high end estimates of both dietary and non-dietary exposures). In addition, the Agency 

retained the additional 10X FQPA safety factor for the protection of infants and children. The 

assessment includes evaluations of risks for various subgroups, including those comprised of 

infants and children. The Agency’s complete risk assessment is found in the propiconazole 

reregistration docket at http://www.regulations.gov, Docket Identification (ID) Number EPAHQ-OPP-2005-0497.

9.0 Occupational Exposure/Risk Pathway

Reference: The occupational exposure and risk assessment was reviewed by the Exposure Science Advisory 

Council, the information provided in this Section comes from:. Metconazole. Occupational and Residential 

Exposure Assessment for Proposed IR-4 Foliar Uses on Bushberries (Crop Subgroup 3-07B) and Tuberous and 

Corm Vegetables (Crop Subgroup 1C). DP380989, N. Tsaur, 2/3/11.

Occupational handler exposure to metconazole is expected for individuals involved in foliar 

applications to bushberries and tuberous and corm vegetables (mixing, loading, and applying). 

Agricultural workers performing typical post-application activities such as scouting, irrigation, 

transplanting/harvesting, etc. may receive exposure to metconazole residues.
Page 40 of 53

9.1 Short- and Intermediate-Term Handler Risk

Metconazole 50 WDG Fungicide can be applied to bushberries and tuberous and corm 

vegetables for foliar disease control via groundboom, aircraft, chemigation, low pressure 

handwand, handgun, or backpack equipment. The proposed use pattern is summarized in Table 

2. Handler exposure is expected to be short- or intermediate-term based on information provided 

on the proposed label. The label states that all handlers must wear the proper personal protective 

equipment (PPE): a long-sleeved shirt, long pants, chemical resistant gloves, shoes, and socks.

The quantitative exposure/risk assessment developed for occupational handlers is based on the 

following exposure scenarios: 

Mixer/Loaders

1. Mixing/loading WDG (dry flowables) to support groundboom applications,

2. Mixing/loading WDG (dry flowables) to support aerial and chemigation applications,

Flaggers

3. Flagging to support aerial application,

Applicators

4. Applying sprays with groundboom equipment,

5. Applying sprays with aerial equipment,

Mixer/Loader/Applicators

6. Mixing/loading/applying sprays with low pressure handwand equipment,

7. Mixing/loading/applying sprays with handgun equipment on a mobile vehicle, and

8. Mixing/loading/applying sprays with backpack equipment.

Unit Exposures

Chemical-specific data for assessing exposure during pesticide handling activities 

(mixing/loading, applying, and mixing/loading/applying) were not submitted to the Agency in 

support of this petition. It is HED policy to use data from PHED Version 1.1 to assess handler 

exposures for regulatory actions when chemical-specific data are not available (HED ExpoSAC 

Policy No. 7, January 1999) or from ORETF. ORETF data were designed to replace the present 

PHED data with higher-confidence, higher quality data that contain more replicates than the 

PHED data for those scenarios. In this assessment, ORETF data was used to assess 

mixing/loading/applying with handgun equipment (data from MRID 44972201).

Summaries of the short- and intermediate-term risks for occupational handlers are included in 

Table 22. The maximum application rate for each exposure scenario is presented as the worst 

case scenario. All handler scenarios (mixer/loader, applicator, and mixer/loader/applicator) 

resulted in short- and intermediate-term MOEs greater than the level of concern (MOEs ranged 

from 19,000 to 340,000 for short-term exposure and 13,000 to 240,000 for intermediate-term 

exposure) at some level of risk mitigation and therefore do not exceed HED’s level of concern.
Page 41 of 53

Table 22. Metconazole Short- and Intermediate-Term Agricultural Occupational Inhalation Exposures and Risks.

Crop

Group Exposure Scenario

Application 

Rate a

Area 

Treated 

Daily b

Inhalation 

Unit 

Exposures c

Inhalation 

Dose d

Short-Term 

Inhalation 

MOE e

Int-Term 

Inhalation 

MOE e

lb ai/A acres μg/lb ai mg/kg/day LOC = 100 LOC = 100

Mixer/Loader

3-07B Mixing/Loading Dry Flowables

for Groundboom Applications 0.078125 80 0.77 0.0000688 130,000 93,000

3-07B Mixing/Loading Dry Flowables

for Aerial and Chemigation Applications 0.078125 350 0.77 0.0003008 30,000 21,000

1C Mixing/Loading Dry Flowables

for Groundboom Applications 0.125 80 0.77 0.0001100 83,000 58,000

1C Mixing/Loading Dry Flowables

for Aerial and Chemigation Applications 0.125 350 0.77 0.0004813 19,000 13,000

Flagger

3-07B Flagging for Aerial Application 0.078125 350 0.35 0.0001367 67,000 47,000

1C Flagging for Aerial Application 0.125 350 0.35 0.0002188 42,000 29,000

Applicator

3-07B Applying Sprays via Groundboom Equipment 0.078125 80 0.74 0.0000661 140,000 97,000

3-07B Applying Sprays via Aerial Equipment 0.078125 350 0.068 0.0000266 340,000 240,000

1C Applying Sprays via Groundboom Equipment 0.125 80 0.74 0.0001057 86,000 61,000

1C Applying Sprays via Aerial Equipment 0.125 350 0.068 0.0000425 210,000 150,000

Mixer/Loader/Applicator

3-07B Mixing/Loading/Applying Liquid Concentrates

with Low Pressure Handwand (PHED) 0.078125 5 30 0.0001674 54,000 38,000

3-07B Mixing/Loading/Applying Liquid Concentrates

with a Backpack (PHED) 0.078125 5 30 0.0001674 54,000 38,000

3-07B Mixing/Loading/Applying Liquid Concentrates

with a Handgun Sprayer (LCO ORETF data) 0.078125 25 1.8 0.0000502 180,000 130,000

1C Mixing/Loading/Applying Liquid Concentrates

with Low Pressure Handwand (PHED) 0.125 5 30 0.0002679 34,000 24,000

1C Mixing/Loading/Applying Liquid Concentrates

with a Backpack (PHED) 0.125 5 30 0.0002679 34,000 24,000

1C Mixing/Loading/Applying Liquid Concentrates

with a Handgun Sprayer (LCO ORETF data) 0.125 25 1.8 0.0000804 110,000 80,000

a Application Rates based on proposed uses for metconazole.

b Acres Treated Per Day is taken from Exposure Science Advisory Council (ExpoSAC) Policy No. 9.1 for all scenarios except Mixing/Loading/Applying with a Handgun. For this scenario, number of 

acres treated was based on professional judgment of ExpoSAC.

c Unit Exposures based on PHED Version 1.1 or ORETF data. Baseline = no respirator.

d Inhalation Dose (mg/kg/day) = daily unit exposure (μg/lb ai) x application rate (lb ai/acre) x amount handled /day (acres/day) x conversion factor (1 mg/1,000 μg) x absorption factor (100%) / body 

weight (70 kg).

e Inhalation MOE = NOAEL (mg/kg/day) / Inhalation Dose (mg/kg/day). Level of concern = 100. ST NOAEL = 9.1 mg/kg/day. IT NOAEL = 6.4 mg/kg/day.
Page 42 of 53

9.2 Short- and Intermediate-Term Postapplication Risk

Agricultural workers performing typical post-application activities such as scouting, irrigation, 

transplanting/harvesting, etc. may receive exposure to metconazole residues. However, since 

there is no dermal endpoint identified up to the limit dose, a dermal post-application assessment 

is not needed.

Occupational postapplication exposure can also occur via the inhalation route. Based on the 

Agency's current practices, a quantitative occupational postapplication inhalation exposure 

assessment was not performed for metconazole at this time. However, there are multiple 

potential sources of postapplication inhalation exposure to individuals performing 

postapplication activities in previously treated fields. These potential sources include 

volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides. 

The Agency sought expert advice and input on issues related to volatilization of pesticides from 

its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in 

December 2009. The Agency received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report as well as available postapplication inhalation exposure 

data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies 

and procedures, to identify the need for and, subsequently, the way to incorporate occupational 

postapplication inhalation exposure into the Agency's risk assessments. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative occupational 

postapplication inhalation exposure assessment for metconazole.

Restricted Entry Interval

REIs are typically based on the acute toxicity of technical chemical material. Under WPS, active 

ingredients classified as acute Toxicity Category III or IV for Acute Dermal and Primary Skin 

Irritation are assigned a 12-hour REI. Thus, the 12-hour REI on the label is acceptable.
Page 43 of 53

Appendix A: Toxicology Assessment

A.1 Toxicology Data Requirements

Table A.1. Metconazole Toxicology Data Requirements

Test Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

870.1200 Acute Dermal Toxicity ..................................................

870.1300 Acute Inhalation Toxicity..............................................

870.2400 Primary Eye Irritation....................................................

870.2500 Primary Dermal Irritation ..............................................

870.2600 Dermal Sensitization......................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)...............................................

870.3150 Oral Subchronic (nonrodent) .........................................

870.3200 21-Day Dermal ..............................................................

870.3250 90-Day Dermal ..............................................................

870.3465 90-Day Inhalation..........................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3700a Developmental Toxicity (rodent)...................................

870.3700b Developmental Toxicity (nonrodent).............................

870.3800 Reproduction .................................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent) ..............................................

870.4100b Chronic Toxicity (nonrodent)........................................

870.4200a Oncogenicity (rat)..........................................................

870.4200b Oncogenicity (mouse)....................................................

870.4300 Chronic/Oncogenicity....................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial.....................

870.5300 Mutagenicity—Gene Mutation - mammalian................

870.5xxx Mutagenicity—Structural Chromosomal Aberrations...

870.5xxx Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotox. (hen) .....................................

870.6100b 90-Day Neurotoxicity (hen)...........................................

870.6200a Acute Neurotox. Screening Battery (rat) .......................

870.6200b 90-Day Neuro. Screening Battery (rat)..........................

870.6300 Develop. Neuro..............................................................

no

no

yes

yes

no

no

no

no

yes

no

870.7485 General Metabolism ......................................................

870.7600 Dermal Penetration ........................................................

870.7800 Immunotoxicity .............................................................

yes

no

yes

yes

yes

yes

Special Studies for Ocular Effects

Acute Oral (rat)...........................................................

Subchronic Oral (rat) ..................................................

Six-month Oral (dog)..................................................

no

no

no

no

no

no
Page 44 of 53

A.2 Toxicity Profiles

Table A.2 Acute Toxicity Profile – Metconazole Technical

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral [mouse] 44721512 LD50 = >566 mg/kg III

870.1100 Acute oral [rat] 44721512 LD50 = >566 mg/kg III

870.1100 Acute oral [rat] 44721513 LD50 = >1459 mg/kg III

870.1100 Acute oral [rat] 44721514 LD50 = >5000 mg/kg IV

870.1200 Acute dermal [rat] 44721512 Dermal LD50 > 2000 III

870.1200 Acute dermal [rabbit] 44721512 Dermal LD50 > 2000 III

870.1200 Acute inhalation [rat] 44721512 LD50 = >5.6 mg/L IV

870.2400 Acute eye irritation [rat] 44721513 moderate irritant III

870.2500 Acute dermal irritation [rabbit] 44721513 mild irritant IV

870.2600 Skin sensitization [guinea pig] 44721513 neg. -

Table A.3 Subchronic, Chronic and Other Toxicity Profile for Metconazole Technical1

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3100 28-Day oral toxicity 

rodents (rat)

44721515 (1990)

M/F: 0, 30, 100, 1000, 3000 

ppm

M: 0, 2.7, 9.1, 90.5, 261.1 

mg/kg/day 

F: 0, 3.1, 10.1, 97, 287.4 

mg/kg/day

Acceptable/guideline

NOAEL (M/F) = 9.1/10.1 mg/kg/day

LOAEL (M/F) = 90.5/97 mg/kg/day based on 

depression of body weight in M, liver and 

kidney weight increases with associated 

histopathological effects (hypertrophy and 

fatty vacuolation) in liver only.

870.3100 90-Day oral toxicity 

rodents (rat)

44721517 (1991)

M/F: 0, 30, 100, 300, 1000, 

3000 ppm

M: 0, 1.94, 6.4, 19.2, 64.3, 

192.7 mg/kg/day 

F: 0, 2.1, 7.2, 22.1, 71.4, 

208.0 mg/kg/day

Acceptable/guideline

NOAEL (M/F) = 6.4/7.2 mg/kg/day

LOAEL (M/F) = 19.2/22.1 mg/kg/day based 

on increased spleen weight in females and 

hepatic vacuolation in males.
Page 45 of 53

Table A.3 Subchronic, Chronic and Other Toxicity Profile for Metconazole Technical1

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3100 90-Day oral toxicity 

rodents (mouse)

44721519 (1991)

M/F: 0, 30, 300, 3000 (wk 

1)/2000(wk 2-13) ppm

M: 0, 9.58, 50.5, 341.1 

mg/kg/day 

F: 0, 6.94, 60.7, 438.5 

mg/kg/day

Acceptable/guideline

NOAEL (M/F) = 9.58/6.94 mg/kg/day

LOAEL (M/F) = 50.5/60.7 mg/kg/day based 

on increase in absolute and relative liver 

weights, hepatocellular hypertrophy and 

vacuolation, and increase in relative spleen 

weight (F), elevated AST and ALT activity. 

870.3150 28-Day oral toxicity 

non-rodents (dog)

44721520 (1991)

M/F: 0, 100, 1000, and 

7000-10000 ppm in diet

Unacceptable/non-guideline 

(some preliminary test data 

provided)

NOAEL (M/F) = 100 ppm in diet

LOAEL (M/F) = 1000 ppm in diet (increase in 

relative and absolute thyroid wt. in one/two 

females)

Deficiencies: low n (2M/2F per dose); 

decrease in food consumption means low 

exposure to test compound; actual dose 

received per dose group not provided.

870.3150 90-Day oral

toxicity non-rodents 

(dog)

44721521 (1991)

M/F: 0, 60, 600, 6000 ppm 

in diet

M: 0, 2.5, 24.4, 225.2 

mg/kg/day

F: 0, 2.6, 24.3, 206.6 

mg/kg/day

Acceptable/guideline

NOAEL (M/F) = 2.5/2.6 mg/kg/day

LOAEL (M/F) = 24.4/24.3 mg/kg/day based 

on decreased food consumption and body 

weight gain in females and elevated platelets 

and reticulocytes in males.

870.3200 21-day Dermal 

Toxicity

46808439 (2006)

0, 250, 500, 1000 

mg/kg/day 

Acceptable/guideline

NOAEL: 1000 mg/kg

LOAEL: > 1000 mg/kg

No evidence of dermal toxicity

870.6200 Subchronic (13-

week) Oral 

Neurotoxicity- rat

46808440 (2002)

0, 50, 170, 500 ppm

M: 0, 4.84, 15.69, 47.08 

mg/kg/day

F: 0, 5.10, 17.62, 49.82 

mg/kg/day

Acceptable/Non-guideline

Systemic NOAEL (M/F) = 4.84/5.10 mg/kg/

Systemic LOAEL (M/F) = 15.69/ 17.62 

mg/kg/ based on decreases in body weight and 

food consumption. 

Neurotoxicity NOAEL (M/F) 47.08/49.82 

mg/kg/day 

870.3700 Prenatal development 

in rodents (rat)

44721522 (1991)

0, 12, 30, 75 mg/kg/day

Gavage

Acceptable/Guideline

Maternal NOAEL = 12 mg/kg/day

LOAEL = 30 mg/kg/day based on decrease in 

body weight gain.

Developmental NOAEL = 12 mg/kg/day

LOAEL = 30 mg/kg/day based on increased 

incidence of skeletal variations 

(predominantly lumbar ribs).
Page 46 of 53

Table A.3 Subchronic, Chronic and Other Toxicity Profile for Metconazole Technical1

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3700 Prenatal development 

in rodents (rat)

46808443 (2002)

0, 1, 4, 16, 64 mg/kg/day

Gavage

Acceptable/Guideline

Maternal NOAEL= 16 mg/kg/day

LOAEL= 64 mg/kg/day based on decreased 

body weight and food consumption, increased 

placental weight and increased incidence of 

swollen placenta.

Developmental NOAEL= 16 mg/kg/day 

LOAEL= 64 mg/kg/day based on based on an 

increase in early and late resorptions, 

decreased fetal body weight and increased 

incidence of incomplete ossification of 

sternebrae.

870.3700 Prenatal 

developmental in 

non-rodents (rabbit)

Definitive Study

44721602 (1997)

0, 5, 10, 20, 40 mg/kg/day 

gavage

Acceptable/Guideline

Maternal NOAEL = 20 mg/kg/day

LOAEL = 40 mg/kg/day based on reductions 

in body weight gain, food consumption, and 

changes in various hematology parameters 

(reductions in hematocrit, hemoglobin, mean 

corpuscular volume and increases in platelet 

counts and alkaline phosphatase activity).

Developmental NOAEL = 20 mg/kg/day

LOAEL = 40 mg/kg/day based on increases in 

post-implantation losses.

870.3700 Prenatal 

developmental in 

non-rodents (rabbit)

44721603 (1991)

0, 4, 10, 25, 62.5 mg/kg/day 

(Exp. #1)

0, 2, 4, 10 mg/kg/day (Exp. 

#2)

Acceptable/Guideline

Maternal NOAEL = 25 mg/kg/day

LOAEL = 62.5 mg/kg/day based on body 

weight changes and slight clinical signs 

(anorexia/reduced or altered fecal output, cold 

ears).

Developmental NOAEL = 4 mg/kg/day

LOAEL = 10 mg/kg/day based on examining 

data from the two experiments. Effects at 62.5 

mg/kg/day show total litter loss, decreased live 

fetuses, increased early and late resorptions. 

Effects at 25 mg/kg/day show some 

malformations: hydrocephaly (4 fetuses from 

4 different litters, but NOT seen at 62.5 

mg/kg/day) and limb effects (2 fetuses from 2 

different litters, with one fetus with same 

effect at 62.5 mg/kg/d). Hydrocephaly and 

limb effects were observed at 10 mg/kg/day in 

Experiment #2, but not at that same dose in 

Experiment #1.
Page 47 of 53

Table A.3 Subchronic, Chronic and Other Toxicity Profile for Metconazole Technical1

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3800 Reproduction and 

fertility effects

2-generation- rat

46808447 (2002)

0, 30, 150 and 750 ppm 

M/F: 0/0, 2/2, 10.8/10.6, 

53.2/53.0 mg/kg/day

Acceptable/Guideline

Parental/Systemic NOAEL (M/F) = 9.8/10.8 

mg/kg/day

LOAEL (M/F) = 49.4/53.2 mg/kg/day based 

on: decreased body weight and decreased 

weight gain in male and female parental 

animals, increased incidence of fatty 

hepatocyte change in male parental animals, 

and increased incidence of spleen congestion 

in F1 parental females. 

Reproductive NOAEL (M/F) = 49.4/ 10.8 

mg/kg/day

LOAEL (M/F) = 53.2 mg/kg/day based on 

increased gestation length and decreased 

gestation index driven by dystocia (difficult 

labor).

Offspring NOAEL (M/F) = 9.8/10.8 

mg/kg/day

LOAEL (M/F) = 49.4/53.2 mg/kg/day based 

decreased viability on lactation day 0 and 

decreased body weight in F2 offspring. 

870.4100a Chronic toxicity 

rodents (rat)

4472109 (1992)

0, 10, 100, 300, 1000 ppm

M: 0, 0.44, 4.3, 13.1, 43.9 

mg/kg/day

F: 0, 0.52, 5.3, 16.0, 53.8 

mg/kg/day

Acceptable/Guideline

NOAEL = (M/F) = 4.3/16.0 mg/kg/day

LOAEL = (M/F) = 13.1/ 53.8 mg/kg/day 

based on an increase in mean adjusted liver 

weights at 12 months (M) and 24 months (F), 

increase in spleen weights at 24 months (F), 

and increased hepatocellular lipid vacuolation 

(M/F) and centrilobular hypertrophy (M/F).

870.4100b Chronic toxicity- dog 44721610

0, 30, 300, 1000, 3000 ppm 

in diet

M: 0, 1.1, 12.0, 38.5, 110.0 

mg/kg/day

F: 0, 1.1, 10.3, 36.8, 113.7 

mg/kg/day

Acceptable/Guideline

NOAEL (M/F) = 12.0/10.3 mg/kg/day

LOAEL (M/F) = 38.5/36.8 mg/kg/day based 

on decreased body weight gain weeks 1-13 

(males), increased alkaline phosphatase 

activity (both sexes) and increased incidence 

of Kupffer cell pigmentation (females).

870.4200a Carcinogenicity -

rat

44721611 (1992)

0, 100, 300, 1000 ppm

M: 0, 4.6, 13.8, 46.5 

mg/kg/day

F: 0, 5.5, 16.6, 56.2 

mg/kg/day

Acceptable/Guideline

Non-neoplastic findings at (M/F) 13.8/56.2 

mg/kg/day: increased incidence of 

hepatocellular lipid vacuolation (M/F), 

centrilobular hypertrophy (M/F), liver pigment 

deposition (M), histiocytic foci in the spleen 

(M/F),and increase in severity of chronic 

renal nephropathy (M). Evidence of 

mononuclear cell leukemia (F).
Page 48 of 53

Table A.3 Subchronic, Chronic and Other Toxicity Profile for Metconazole Technical1

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.4200b Carcinogenicitymouse44721612 (1992)

0, 30, 300, 1000 ppm

M: 0, 4.5, 39.5, 166.9 

mg/kg/day

F: 0, 5.9, 58.1, 195.5 

mg/kg/day

Acceptable/Guideline

Non-neoplastic findings at (M/F) 166.9/58.1 

mg/kg/day: increase in vacuolation, 

hypertrophy, splenic atrophy and adrenal 

corticomedullary pigmentation, sinusoidal 

hypercellularity/single cell necrosis. 

Neoplastic findings: increase in liver cell 

tumors at high dose (M/F): Increased 

incidence of hepatocellular adenomas in males 

and hepatocellular carcinomas in females. 

870.5100 Salmonella 

typhimurium and 

Escherichia coli

Reverse Mutation 

Assay

44721613 (1990)

Up to limit dose of 5000 

μg/ plate (S. typhimurium) 

and (E. coli) in the 

presence and absence of 

metabolic activation

(+ S9)

Acceptable/Guideline

Test material was not cytotoxic with or 

without S9 activation in five S. typhimurium

strains and one strain of E. coli, and did not 

induce a genotoxic response in any strain.

870.5300 In vitro Mouse 

Lymphoma 

Mutagenesis Assay

WL136184*

*cis only isomer

44721615 (1991)

Six doses up to 125 μg/ml 

(toxicity was observed 

above that dose) in the 

presence and absence of 

metabolic activation 

(+ S9)

Acceptable/Guideline

There was no evidence of biologically 

significant induction of mutant colonies. 

870.5375 In vitro Cytogenetics 

Test

44721616 (1991)

From 6.25 to 400 g/ml, 

with and without metabolic 

activation (+ S9) 

Acceptable/Guideline

Weakly positive (induced chromosome 

aberrations in Chinese hamster ovary cells) in 

the presence of S9 activation, negative without 

S9 activation. 

870.5395 In vivo Mammalian 

Erythrocyte 

Micronucleus Test: 

Mouse

44721618 (1995)

Up to the limit dose of 2000 

mg/kg

Acceptable/Guideline

There was no statistically significant increase 

in the frequency of micronucleated 

polychromatic erythrocytes in mouse bone 

marrow at any dose or collection time.

870.5550 In vivo/in vitro

Mammalian UDS test

Rat

44721620 (1995)

Up to the limit dose of 2000 

mg/kg

Acceptable/Guideline

Negative for unscheduled DNA synthesis.

870.6200b Subchronic 

Neurotoxicity- rat

46808440 (2002)

0, 50, 170, 500 ppm

M: 0, 4.84, 15.69, 47.08 

mg/kg/day

F: 0, 5.10, 17.62, 49.82 

mg/kg/day

Acceptable/Non-guideline

Systemic NOAEL (M/F) = 4.84/5.10 mg/kg/

Systemic LOAEL (M/F) = 15.69/ 17.62 

mg/kg/ based on decreases in body weight and 

food consumption. 

Neurotoxicity NOAEL (M/F) 47.08/49.82 

mg/kg/day 
Page 49 of 53

Table A.3 Subchronic, Chronic and Other Toxicity Profile for Metconazole Technical1

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.7485 Metabolism and 

pharmacokinetics: rat

44721622 (1992)

single high dose: 164 

mg/kg

Radiolabel: 

(cyclopentyl14C )

Acceptable/Guideline

Approximately 94% of radioactivity in excreta 

after five days: feces (males - 81.3%, females 

- 65.5%) and urine (males - 13.6%, females -

28.4%)

870.7485 Metabolism and 

pharmacokinetics: rat

44721623 (1991)

single low dose: 2 mg/kg

Radiolabel: 

(cyclopentyl14C)

Acceptable/Guideline

Approximately 94% of radioactivity in excreta 

after 72 hrs: feces (males - 80%, females -

67%) and urine (males - 14.8%, females -

26%). Metabolite information presented.

870.7485 Metabolism and 

pharmacokinetics: rat

WL136184*

*cis only isomer

44721624 (1991)

single high dose: 200 

mg/kg (males only)

Radiolabel: 

(Triazole -

14C)

Acceptable/Guideline

Approximately 96% of radioactivity in excreta 

after seven days: feces (76%) and urine (20%). 

Metabolite information presented.

870.7485 Metabolism and 

pharmacokinetics: rat

WL136184*

*cis only isomer

44721625 (1991)

single low dose: 2 mg/kg

Radiolabel: 

(Cyclopentyl -

14C)

Acceptable/Guideline

Excretion/retention in bile-duct cannulated 

rats. Approximately 80% of radioactivity was 

excreted in the bile after 48 hrs: males (78.7%) 

and females (83.3%). 

870.7485 Metabolism and 

pharmacokinetics: rat

46808449 (2002)

male/female rat

single low dose: 2 mg/kg

single high dose: 200 

mg/kg

repeated dose: 2 mg/kg

Acceptable/Non-guideline

Low potential for bioaccumulation following 

single or multiple dosing regimen. The time 

to maximum plasma concentration for male 

and female rats treated with either 2 mg/kg or 

200 mg/kg was the earliest sampling interval, 

0.25 hours and 4 hours, respectively The 

plasma half-life of low- and high-dose rats 

was slightly shorter in males than females, 

~20-25 hours and ~34 hours, respectively.

870.7600 In Vivo Dermal 

Penetration Study

46808450 (1990)

Acceptable/Non-guideline

Dermal absorption= 16% (72 hrs)

870.7800 Immunotoxicity 

Study: male rat

48107301 (2010)

0, 70, 210, 6300 ppm

0, 5.4, 17, 52 mg/kg/day

Acceptable/Guideline

Systemic 

NOAEL: 17 mg/kg/day.

LOAEL: 52 mg/kg/day based on reduced 

body weight gain at day 7 and 14 of the study. 

Immunotoxicity 

NOAEL: 52 mg/kg/day. 

LOAEL: > 52 mg/kg/day

Effects on rat/mice 

liver enzymes

WL136184*

*cis only isomer

44721626 (1991)

0, 300 ppm in diet (mice) 

and 0, 1000 ppm in diet 

(rats) for seven or 28 days 

Acceptable/Non-guideline

Increased liver weight, cytochrome P450, 

ethoxycoumarin O-deethylase, ethylmorphine 

N-demethylase, and lauric acid 11-

hydroxylase in both rats and mice. No effect 

on ethoxyresorufin O-deethylase, palmitoylCoA oxidation, or peroxisome proliferation (in 

terms of peroxisome number or morphology). 
Page 50 of 53

Table A.3 Subchronic, Chronic and Other Toxicity Profile for Metconazole Technical1

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

14-day Mechanistic 

Study

46665403 (2004)

0, 30, 300, 1000 ppm in 

diet (mice) for 14 days.

F: 4.5, 48, 151 mg/kg/day

Acceptable/Non-guideline

Increased liver weight (300 and 1000 ppm); 

increased hepatic drug metabolizing enzymes 

(300 and 1000 ppm) after 7 days; enlarged 

livers (1000 ppm) at days 3, 7 and 14; hepatic 

hypertrophy and vacuolation (300 and 1000 

ppm) at day 14; increased ALT and AST 

activities at 1000 ppm (day 14); increased 

lipid peroxide (300 and 1000) at day 14; 

increased PCNA labeling at 1000 ppm at day 

3 and 7. 

1

cis/trans ratio is 85:15. All studies used cis/trans mixture unless otherwise noted.
Page 51 of 53

Appendix B: EPA Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These studies (which compose PHED, 

listed below) were determined to require a review of their ethical conduct, have received that 

review and have been determined to be ethical.

The PHED Task Force, 1995. The Pesticide Handlers Exposure Database, Version 1.1. Task Force 

members Health Canada, U.S. Environmental Protection Agency, and the National Agricultural Chemicals 

Association, released February, 1995.

Appendix C: Structure, Nomenclature, and Physical and Chemical Properties

Table C.1. Metconazole Nomenclature.

Chemical structure

N

N

N

H3C

H3C

HO

Cl

cis-isomer

N

N

N

H3C

H3C

HO

Cl

trans-isomer

Common name Metconazole

Company experimental name KNF-S-474m (Kureha); BAS 555 F (BASF); V-10116 (Valent)

IUPAC name (1RS,5RS:1RS,5SR)-5-(4-chlorobenzyl)-2,2-dimethyl-1-(1H-1,2,4-triazol-1-

ylmethyl)cyclopentanol

CAS name 5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-

ylmethyl)cyclopentanol

CAS registry number 125116-23-6 (cis- and trans-isomers)

115850-27-6 (cis-isomer)

115850-28-7 (trans-isomer)

End-use products (EP) 50% WDG (Metconazole 50 WDG Fungicide, EPA File Symbol 59639-147)

Table C.2. Physicochemical Properties of Metconazole

Parameter Value References*

(MRID)

Melting point/range 100.0-108.4°C (using Electrothermal Digital Melting 

Point Apparatus) (AC900,768 technical grade)

44721505

pH 5.81 at 25oC (1% aqueous suspension) 46808402

Relative density (20°C) 1.14 (relative density to water at 4°C, using capillarystoppered, density-specific gravity bottle) (Lot No. 

AC 8879-140B)

44721505

Water solubility (20oC) Using shake-flask method:

18.7 ± 1.0 mg/L (cis-isomer, WL148271, KNF-S-474m)

13.6 ± 1.7 mg/L (trans-isomer, WL148271, KNF-S474m)

44721505
Page 52 of 53

Table C.2. Physicochemical Properties of Metconazole

Parameter Value References*

(MRID)

Solvent solubility (g/L) at 

20oC

Solvent Metconazole cis trans 44721505

acetone 363 251 117

methanol 403 294 117

dichloromethane 481 343 141

ethyl acetate 260 173 90.0

propanol 132 86.6 46.7

toluene 103 66.2 38.0

Hexane 1.40 0.929 0.483

Vapor pressure (20°C) Using gas-saturation method:

< 1.23x10-5Pa or 9.23 x 10-8 mm Hg (metconazole)

< 1.04x10-5Pa or 7.80 x 10-8 mm Hg (cis-isomer)

< 1.96x10-6Pa or 1.47 x 10-8 mm Hg (trans-isomer)

44721505

Dissociation constant (pKa) 11.38±0.03 and 1.06±0.03 (in water at 29.1°C using 

spectrophotometric method; Lot No. AC 8879-140B) 

44721505

Octanol/water partition 

coefficient, Log(KOW)

At 20 oC (using flask shaking method):

Kow (log Kow) = 7090±989 (3.85) (Lot No. AC 8879-

140B) (TGAI)

Kow (log Kow) = 7150±803 (3.85) (cis-isomer, CL 

354,801)

Kow (log Kow) = 6800±1700 (3.8) (trans-isomer, CL 

354,802)

44721505

UV/visible absorption 

spectrum

pH λ A log ε 46808403

cis-isomer

2.0 221.4 0.828 4.03

6.8 0.8452 4.04

7.0 0.9126 4.08

10.3 0.7226 3.98

trans-isomer

2.0 221.4 0.9053 4.07

7.0 0.9547 4.10

10.1 0.9893 4.11

* Product Chemistry Reviews: DP #256877, Shyam Mathur, Ph.D., 9/12/2000 and DP #329168, Shyam Mathur, 

Ph.D., 7/13/07.
Page 53 of 53

Appendix D: International Residue Limit Status

Metconazole (PC Code 125619; 03/08/11)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition: 

US Canada Mexico2 Codex3

40 CFR 180.617:

Plants/Livestock: Metconazole [5-[(4-

chlorophenyl)methyl]-2,2-dimethyl-1-

(1H-1,2,4-triazol-1-

ylmethyl)cyclopentanol] as the sum of 

its cis- and trans- isomers

None None

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex

Vegetable, tuberous and corm, 

subgroup 1C

0.04

Bushberry subgroup 13-07B 0.4

Completed: M. Negussie; 03/10/2011

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.