### Page **1** of **58** UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460 **OFFICE OF CHEMICA** **L SA FETY**  **AND POLLUTION PREVENTION**  

### MEMORANDUM **D ATE**  **:** Dec ember 15 , 201 4 **SUBJECT: Metconazole** 

– Human Health Risk Assessment for a Section 3 Registration of

N ew U ses on Dry

Shelled Pea and Beans (Except Soy bean) Crop Subgroup 6C and Sunflower Crop Subgroup 20B; Crop Group Expansion to Rapeseed Subgroup 20A; and Crop Group Conversions to Fruit, Stone, Group 12 - 12; and Nut, Tree, Group 14 - 12. **PC Code:** 12 5619 **DP Barcode:** D 4 18671 **Decision No.:** 48 7580 **Registration No. :**  59639 - 147 **Petition No .:**  4 E8 2 44 **Regulatory Action:** Section 3 Registration **Risk A**  **ss essment Typ**  **e :**  Single Chemical/Aggregate **Case No.:** NA **T XR No.:**  NA **CAS No.:** 1 25116 - 23 - 6 **MRID No.:** NA **40 CFR:** 180. 617 

### FROM: Barry

O’Keefe , Senior Biologist My ron S. Ottley , Senior Bi ologist Nancy Dodd , Chemist Kristin Rury , Biologist Risk Assessment Branch III (RAB III) Health Effects Division (7509P) **THROUGH:** Christin e Olinger , Branch Chief

Risk Assessment Branch III (RAB III) Health Effects Division (7509P) **TO:** Laura Nollen , Risk Man ager

Barbara Madden, Branch Chief Risk Integration, Minor Use and Emergency Response Branch (RIMUERB) Registration Division (7505P) And Hope Johnson, PM21 Fungicide Branch Registration Division (7505P)

### Page **2** of **58**

This document and attachments provide an assessment of the human health risk resulting from the proposed and registered uses of metconazole . The toxicology reevaluation was performed by My ron Ottley , the drinking water assessment was conducted by Faruque Khan (EPA Environmental Fate and Effects Division (EFED)), the review of the residue chemistry data an d dietary exposure assessment w ere conducted b y Nancy Dodd , the occupational and residential exposure assessment was conducted b y Kristin Rury , and the human health risk assessment w as conducted b y Barry

O’Keefe .

### Page **3** of **58 Table of Contents**  **1.0 Executive Summary**  ................................ ................................ ................................ ........... 5 **2.0 HED Recommendations**  ................................ ................................ ................................ .... 8 **2.1 Da**  **ta Deficiencies** ................................ ................................ ................................ ............ 8 **2.2.1 Enforcement Analytical Method**  ................................ ................................ ............... 8 **2.2.2 Recommended Tolerances**  ................................ ................................ ......................... 9 **2.2.3 Revisions to Petitioned**  **- For Tolerances**  ................................ ................................ .... 9 **2.2.4 International Harmonization**  ................................ ................................ ..................... 9 **2.2.5 Label Modifications**  ................................ ................................ ................................ .. 10 **3.0 Introduction**  ................................ ................................ ................................ ...................... 10 **3.1 Chemical**  **Identity** ................................ ................................ ................................ ......... 10 **3.2 Physical/Chemical Characteristics**  ................................ ................................ ............. 11 **3.3 Pesticide Use Pattern**  ................................ ................................ ................................ .... 11 **3.4 Anticipated Exposure Pathways**  ................................ ................................ ................. 17 **3.5 Consideration of Environmental Justice**  ................................ ................................ .... 17 **4.0 Hazard Characterization and Dose**  **- Response Assessment**  ................................ .......... 17 **4.1 Summary of Toxicological Effects**  ................................ ................................ .............. 18 **4.2 Safety Factor for Infants and Children (FQPA Safety Factor)**  ............................... 20 **4.2.1 Completeness of**  **the Toxicology Database** ................................ .............................. 20 **4.2.2 Evidence of Neurotoxicity**  ................................ ................................ ........................ 20 **4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal**  ........ 20 **4.2.4 Residual Uncertainty in the Exposure Database**  ................................ ................... 20 **4.3 Toxicity Endpoint**  **and Point of Departure Selections** ................................ .............. 21 **4.3.1 Dose**  **- Response Assessment**  ................................ ................................ ...................... 21 **4.3.2 Recommendation for Combining Routes of Exposure for Risk Assessment**  ...... 22 **4.3.3 Cancer Classification and Risk Assessment Recommendation**  ............................ 23 **4.3.4 Summary of Points of Departure and**  **Toxicity Endpoints Used in Human Risk Assessment**  ................................ ................................ ................................ ............................... 23 **5.0 Dietary Exposure and Risk Assessment**  ................................ ................................ ......... 25 **5.1 Residues of Concern Summary and Rationale**  ................................ .......................... 25 **5.2 Food Residue Profile**  ................................ ................................ ................................ .... 26 **5.3 Water Residue Profile**  ................................ ................................ ................................ .. 27 **5. 4**  **Dietary Risk Assessment** ................................ ................................ .............................. 28 **5.4.1 Description of Residue Data Used in Dietary Assessment**  ................................ .... 28 **5.4.2 Percent Crop Treated Used in Dietary Assessment**  ................................ .............. 29 **5.4.3 Acute Dietary Risk Assessment**  ................................ ................................ ............... 29 **5.4.4 Chronic Dietary Risk Assessments**  ................................ ................................ ......... 29 **5.4.5 Summary Table**  ................................ ................................ ................................ ......... 29 **5.4.6 Dietary Assessment of Free Triazole and its Conjugates**  ................................ ...... 30 **6.0 Residential (Non**  **- Occupational) Exposure/Risk Characterization**  ............................. 30 **6.1 Residential Handler Expo**  **sure** ................................ ................................ .................... 30 **6.2 Post**  **- Application Exposure**  ................................ ................................ .......................... 30 **6.3 Residential Risk Estimates for Use in Aggregate Assessment**  ................................ .. 32 **6.4 Residential Bystander Post**  **- application Inhalation Exposure**  ................................ . 32 **6.5 Spray Drift**  ................................ ................................ ................................ .................... 33

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**7.0 Aggregate Exposure/Risk Characterization**  ................................ ................................ .. 33 **7.1 Acute Aggregate Risk**  ................................ ................................ ................................ ... 33 **7.2 Short** **- Term Aggregate Risk**  ................................ ................................ ........................ 33 **7.3 Chronic Aggregate Risk**  ................................ ................................ .............................. 34 **8.0 Cumulative Exposure/Risk Characterization**  ................................ ............................... 34 **9.0 Occupational Exposure/Risk Characterization**  ................................ ............................ 35 **9.1 Short** **- /Intermediate**  **- Term Handler Risk**  ................................ ................................ ... 35 **9.2 Short** **- and Intermediate**  **- Term Post**  **- Application Risk**  ................................ .............. 36 **9.2.1 Dermal Post**  **- Application Risk**  ................................ ................................ ................. 36 **9.2.2 Inhalation Post** **- Application**  **Risk** ................................ ................................ ............ 37 **10.0 References**  ................................ ................................ ................................ ......................... 38 **Appendix A. Toxicology Profile and Executive Summaries** ................................ .................. 39 **A.1 Toxicology Data Requirements**  ................................ ................................ ................... 39 **A.2 Toxicity Profiles**  ................................ ................................ ................................ ............ 40 **Appendix B. Physicochemical Properties of Metconazole.** ................................ .................... 47 **Appendix C. Review of Human Research** ................................ ................................ ................ 48 **Appendix D. Residential Handler and Post -**  **application Exposu re and Risk Estimates**  ..... 49 **Appendix E. Occupational Handler Exposure and Risk Estimates** ................................ ...... 51 **Appendix F. Summaries of Field Residue Data** ................................ ................................ ...... 55 **Appendix G. International Residue Limits Status Sheet** ................................ ....................... 58

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**1.0 Executive Summary**  Introduction Metconazole is a broad - spectrum triazole fungicide that works s ys temicall y by preventing spore formation and inhibiting mycelial growth. Metconazole acts primaril y as an inhibitor of ergosterol bios ynthesis, thereb y interfering with synthesis of fungal cell membranes and providing s ys t emic seed and seedling protection. Metconazole is currently registered on numerous agricultural crops and on turf and ornamentals in residential settings . Use Profile The Interregional Research Project No. 4 (IR - 4) has proposed for use of metconazole at a maximum single application rate of 0.125 lb ai/A for d ry s helled p ea and b ean (except s oy bean) c rop s ubgroup 6C and s unflower c rop subgroup 20B. IR - 4 is also proposing f or the expansion of rapeseed crop s ubgroup 20A, and the conversion of s tone f ruit crop group 12 - 12 , the maximum single registered application rate is 0.125 lb ai/A. For the crop group conversions of tree nut crop group 14 - 12, the maximum single application rate is 0.11 lb ai/A. The maximum proposed/registered yearly application rates range from 0.125 lb ai/A to 0.50 lb ai/A. Applicators and other handlers must wear long - sleeved shirts, long pants, chemical resistant gloves, socks, and shoes. Metconazole may be applied using ground, aerial, airblast, chemigation, and handheld equipment. The proposed restricted entry interval (REI) is 12 hours. Exposure Profile Exposure pathways include dietary (food and drinking water), residential, and occupational exposure sources. Dietary exposures are expected for acute and chronic durations. Existing residential u se s result in short - term handler exposures for adults, and short - term post - application exposures for adults and children . Occupational handler and post - application exposures are expected for short - and intermediate - term durations. H azard Assessment The liver is the primary

target organ (with observed effects such as increased liver weight and enzy me activity , increased incidence of hyp ertrophy and vacuolization) in the mouse, rat , and dog following oral exposure to metconazole durin g subchronic or chronic exposure durations. Other adverse effects observed in oral studies were decreased body weight, and blood effects (reductions in ery

throcy te and/or platelet parameters) in the mouse, rat, dog , and/or rabbit. Splenic effects including increased spleen weight and hy perplasia 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) . Metconazole is considered nongenotoxic and is classified as "not likel y to be carcinogenic to humans" based on an absence of tumors in rats and mice. Developmental studies in rabbits show evidence of developmental effects, but only at dose levels that are maternall y toxic. There is qu antitative evidence of susceptibility in the rat developmental study ; however, the concern is low since the developmental effects are well characterized, the no observable adverse effect levels (NOAELs) are well defined, and that dose/endpoint is used for acute dietary risk assessment for the sensitive population. Metconazole did not demonstrate the potential for neurotoxicity in any of the four species (mouse, rat, dog and

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rabbit) in the database. For these reasons, th e Food Quality Protection Act ( FQPA) Safety Factor has been reduced to 1X. In accordance with the revised 40 CFR Part 158 data requirements, a subchronic inhalation study is required for this risk assessment but was not included in the existing database; therefore, a 10X database uncertainty factor has been applied to inhalation exposure scenarios ( HASPOC, TXR0057053 , J. Leshin , 10/09/2014 ) . Dietary Exposure The residue chemistry

and environmental fate data are adequate to assess human dietary exposure . The assessments are based on reliable data and will not underestimate exposure or risk. E stimated drinking water concentrations (EDWCs) were incorporated directly into the dietary exposure assessments. S ince no observed effects could be attributed to a single dose for the general population, including infants and children , an acute endpoint was not established. Therefore, an acute dietary exposure assessment was not conducted for these population groups . However, an unrefined acute dietary (food and drinking water) anal ys is was conducted for females 13 to 49 ye ars old. Results of the anal ys is are below HED’s level of concern (LOC). The acute dietary exposure for food and drinking water for females 13 to 49 years old is 4.6 % of the acute P opulation Adjusted Dose (aPAD). The results of the unrefined chronic dietary (food and drinking water) analy sis are below HED ’s LOC for all population subgroups. The dietary exposure for food and drinking water for the general U.S. population is 6.6 % of the chronic Population Adjusted Dose (c PAD) and 14 % of the cPAD for children 1 to <2 ye ar s old , the population subgroup with the highest estimated chronic dietary exposure to metconazole . Residential Exposure N o n ew residential uses were requested in this action . However, metconazole is currentl y registered for use on residential turf and ornamentals . Residential exposure s from existing residential use s w ere re assessed using the updated 2012 HED Residential Standard Operating Procedures 1 

### (SOPs). Residential exposure is expected to be short - term onl y. Because dermal toxicity endpoints for the appropriate duration of exposure (short - term) were not identified up to the limit dose, only adult residential handler inh alation exposures, and residential post application incidental oral exposures for children have been assessed. All residential handler inhalation exposure risk estimates were not of concern to HED (i.e. , all margins of exposure (MOEs) >1 ,000 ) , with MOE values rang ing from 6,300 to 23,000,000 . All residential post - application incidental oral exposure risk estimates were also not of concern to HED (i.e. , all MOEs >100) , with M OEs rang ing from 1,00 0 to 450 ,000. Aggregate Exposure There is potential for short - term and chronic aggregate exposure to metconazole . The short - term aggregate exposure results from dietary (which is considered background exposure) and residential (which is considered primary) exposure pathway s. The chronic aggregate exposure is the same as chronic dietary exposure from food and drinking water, which are all below the 1 http://www.epa.gov/pesticides/science/residential - exposure - sop.html

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HED’s level of concern. The short - term aggregate MOE of 63 0 for children 1 to <2 ye ars old is not of concern to HED. For adults, oral dietary and inhalation risk estimates were co mbined using the total aggregated risk index (ARI) methodology since the LOCs for oral dietary exposure (100) and inhalation exposure (1 , 000) ar e different. The LOC ARIis 1; therefore, ARI s of less than 1 are risk estimates of concern. The short - term aggregate ARIof 5. 3 is not of concern to HED. Occupational Exposure Although occupational dermal exposure is expected during treatment of agricultural crops , dermal hazard was not identified for metconazole . Therefore, a quantitative handler dermal risk assessment was not conducted. For the proposed use pattern of metconazole, all short - and intermediate - term occupational handler inhalation MOEs are not of concern at baseline personal protective equipment (PPE) except for mixing/loading water dispersible granules (WDG) for aerial application to canola (crop subgroup 20A), sunflower (crop subgroup 20B), and dry beans and peas (crop subgroup 6C) (short - term MOE = 540; intermediate - term MOE =1,900; LOC = 1,000). With the addition of a PF5 respirator, mixing/loading WDG for aerial application to these crops is not of concern (MOE = 2,700). Based on the Agency's current practices, a quantitative occupational post - appli cation inhalation exposure assessment was not performed for metconazole at this time. I f new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post - application inhalation exposure assessment for metconazole . Although occupational dermal exposure is expected following treatment of agricultural crops, dermal hazard was not identified for metconazole. Therefore, a quantitative post - application dermal risk assessment was not conducted. The 12 hour res tricted entry interval (REI) listed on the label is ad e quate for worker protection . 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 chemic al. These data, which include studies from the Pesticide Handlers Exposure Database , Version 1.1 (PHED 1.1), the Agricultural Handler Exposure Task Force (AHETF) database, the Outdoor Residential Exposure Task Force (ORETF) , and the Residential SOPs (lawns and turf) are subject to ethics review pursuant to 40 CFR 26, have received that review, and are compliant with applicable ethics requirements. For certain studies that review may have included review by the Human Studies Review Board. Descriptions of data sources as well as guidance on their use can be found at http://www.epa.gov/pesticides/science/handler- exposure - data.html and http://www.epa.gov/pesticides/science/post - app - exposure - data.html . Environmental Justice Considerations Potential areas of environmental justice concerns, to the extent possible, were consid ered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and L ow - Income Populations," (http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf .

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**2.0 HED**  **Recommendations** HED has examined the toxicology , residue chemistry , and exposure database s for metconazole . Pending submission of a revised Section B and a revised label as described in section 2.2.5 , there are no toxicology

or residue chemistry

issues that would preclude granting the requested registration and establishing the recommended tolerances for metconazole on the pea and bean, dried shelled, except so ybean, subgroup 6C and the sunflower subgroup 20B; expansion of the canola tolerance to the rapeseed subgroup 20A; and conversion of the established tolerances and registrations for the stone fruit crop group 12 and tree nut crop group 14 to the stone fruit crop grou p 12 - 12 and the tree nut crop group 14 - 12 . Additional data are needed, as outlined below in Section 2.1. The specific tolerance recommendations a re discussed in Section 2.2 . **2.1 Data Deficiencies**  870.3465 Subchronic Inhalation S tudy

 A subchronic inhalation study is required because the use of an oral point of departure (POD) for inhalation exposure results in MOEs as low as 3 8 0 for occupational exposure, which does not meet the target of 1000 for a waiver (TXR005 7053 , J . Leshin , 10 /0 9 /201 4 ). Therefore , a 10X database uncertainty factor has been added for inhalation exposures in the absence of the required inhalation toxicity study . **Data that may be required for future uses** If additional uses increase the dairy cattle dietary

burden, additio nal ruminant feeding studies conducted at higher rates may be needed. **2.2 Tolerance Considerations**  **2.2.1 Enforcement Analytical Method**  An adequate gas chromatography method with nitrogen - phosphorus - detection ( GC/NPD ) method, Valent Method RM - 41C - 1 - 1, is available for enforcement of tolerances for residues of metconazole ( cis - and trans - isomers) in plant commodities. A confirmatory liquid chromatography/tandem mass spectrometry ( LC/MS/MS ) method, Method RM - 41C - 4, is available. For both methods, the rep orted limit of quantitation ( LO Q ) is 0.02 ppm for each isomer in each matrix. The method has been validated b y the ACB/BEAD and was found adequate for enforcing tolerances for residues of metconazole in plant commodities. No radiovalidation data were sub mitted for method RM - 41C - 1 - 1; however, HED has concluded that because the extraction solvent used for the proposed enforcement method is similar to the aqueous organic solvent mixtures used in the plant metabolism studies, radiovalidation of the method is not required. An adequate GC/NPD method is available for enforcement of tolerances for residues of metconazole ( cis - and trans - isomers) in livestock commodities. The enforcement method is a modified version of the German multiresidue method DFG S19. The LOQ is 0.01 ppm for each

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isomer in each matrix, for an LOQ of 0.02 ppm for total metconazole residues. An acceptable confirmatory

procedure ( gas chromatography/mass spectrometry ( GC/MS ) ) is included for the method. The method has been validated b y ACB/B EAD and was found adequate for enforcing tolerances for residues of metconazole ( cis - and trans - isomers) in/on livestock commodities. No radiovalidation data were submitted; however, because DFG S19 is an established multiresidue method, these data are no t required. **2.2. 2**  **Recommended Tolerances** The petitioner’s proposed residue definition (tolerance expression) is adequate and is consistent with the S. Knizner memo dated 5/27/09. A summary of the proposed and recommended tolerances may

be found in Table 2.2.2 below. **Table 2.2.2**  **. Tolerance Summary for Metconazole.**  **Comm odity**  **Established/**

**Proposed Tolerance**  **(ppm) HED** 

**Recommended Tolerance**  **(ppm) Comments** 

**( correct commodity definition**  **)** P e a and b ean , drie d s h elle d , e x cep t so y

b ean , sub gro u p 6 C 0.15 0.15 The 0.15 ppm level h armo niz es with the C ana dian M RL. Sun flo we r s ub gro u

p 20 B 0.9 0.7 Rap esee d sub gro u

p 20 A 0.04 0.08 The 0.08 ppm level h armo niz es with the C ana dian M RL. F r uit , sto n e , gro u

p 1 2 - 1 2 0.2 0.2 Nut , tree , gro u

p 14 - 1 2 0.04 0.04 C anol a see d 0.04 None Remove upon establishment of rapeseed subgroup 20A tolerance. F r uit , sto n e , gro u

p 1 2 0.20 None Remove upon establishment of fruit, stone, group 12 - 12 tolerance. Nut , tree , gro u

p 1 4 0.04 None Remove upon establishment of nut, tree, group 14 - 12 tolerance P istac hi o 0.04 None Remove upon establishment of nut, tree, group 14 - 12 tolerance 

### 2.2. **3 Revisions to Petitioned**  **- For Tolerances**  The proposed tolerance on the sunflower subgroup 20B is 0.9 ppm; HED is recommending a decrease to 0.7 ppm based on the Office of Economic Cooperation and Development ( OECD ) tolerance calculation procedures. The proposed tolerance for the rapeseed subgroup 20A is 0.04 ppm. HED is recommending an increase to 0.08 ppm to harmonize with the C an adian M RL. B ase d o n calculatio n s u sing th e OEC D c alculato r fo r canola, a toleran c e o f 0.0 4 pp m wo ul d h av e b een recommended. **2.2. 4**  **International Harmonization** There are no Codex maximum residue limits (MRLs) established for metconazole.

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Residue definitions are harmonized with Canada. Tolerances in the US are established for residues of metconazole, including its metabolites and degradates. In both the US and Canada, compliance with the tolerance/MRL levels is determined by measuring only metconazole. The recommended tolerance levels are harmonized with Canada. Refer to the International Residue Limits (IRL) table in Appendix G . **2.2. 5**  **Label Modifications** 860.1200 Directions for Use The Section B/label (EPA Reg. No. 59639 - 147) must be revised to include the following statement for the dried shelled pea and bean, except soy bean, subgroup 6C: “Do not appl y to cowpea or field pea used for livestock feed.” The Section B/label should be revised to include the interval between applications for pecan and pistachio. HED recommends that a PF5 respirator be required when mixing/loading WDG metconazole (EPA Reg. No. 59636 - 147) for use on c anola ( c rop s ubgroup 20A), s unflower ( c rop s ubgroup 20B), and dry b eans and p eas ( c rop s ubgroup 6C) . **3.0 In**  **troduction** Metconazole is a broad - spectrum triazole fungicide that works s ys temicall y by preventing spore formation and inhibiting mycelial growth. Metconazole acts primari ly as an inhibitor of ergosterol bios ynthesis, thereb y interfering with synthesis of fungal cell membranes and providing s ys temic seed and seedling protection. Metconazole is currently

registered on numerous agricultural crops and on turf and ornamentals in residential settings. With the current action , the Interregional Research Project No. 4 (IR- 4), on behalf of the IR - 4 Project and the Agricultural Experiment Stations of Montana, South Dakota, North D akota , an d C olorado (dry b ean) , M o ntan a , S o uth D akota , Idah o , an d N orth D akot a (dry p e a) , an d Kan sas , M o ntan a , S o uth D akot a a n d N orth D akot a (s un flower), re qu ested the establishment of permanent tolerances and registration for use on the pea and bean, dried shelled, except soy bean, subgroup 6C, and the sunflower subgroup 20B; expansion of the canola tolerance to the rapeseed subgroup 20A; and conversion of the establ ished stone fruit crop group 12 and tree nut crop group 14 to the stone fruit crop group 12 - 12 and the tree nut crop group 14 - 12. **3.1 Chemical Identity**  The chemical structure and nomenclature of metconazole are presented in Table 3.1.

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**Table 3.1. Metconazole Nomenclature.**  Chemical Structure

cis - isomer trans - isomer Common name Metconazole Com pany experimental name KNF - S - 474m (Kureha); BAS 555 F (BASF); V - 10116 (Valent) IUPAC name (1 RS,5 RS;1 RS,5 SR ) - 5 - (4 - chlorobenzyl) - 2,2 - dimethyl - 1 - (1 H - 1,2,4 - triazol - 1 - ylmethyl)cyclopentanol CAS name 5 - [(4 - chlorophenyl)methyl] - 2,2 - dimethyl - 1 - (1 H - 1,2,4 - triazol - 1 - ylmethyl)cyclopentanol CAS # 125116 - 23 - 6 ( cis - and trans - isomers) 115850 - 27 - 6 ( cis - isomer) 115850 - 28 - 7 ( trans - isomer) End - use product/EP Metconazole 50 WDG Fungicide (EPA Reg. No. 59639 - 147), a water - dispersible granule formulation containing 50% active ingredient. Quash 50 WDG (EPA Reg. No. 59639 - 147), also k nown as V - 10116 50 WDG 

### 3.2 **Physical/Chemical Characteristics** If released to air, a vapor pressure of 1.23x10 - 5 

### Pa or 9.23 x 10 - 8 

### mm Hg indicates metconazole will exist solely

in the particulate phase in the atmosphere. Particulate - phase metconazole will be removed from the atmosphere b y wet or dry deposition. Metconazole will not volatilize from dry soil surfaces based upon its vapor pressure. The phy siochemical properties of metconazole are summarized in Appendix B. **3.3 Pesticide Use Pattern**  Metconazole 50 WDG Fungicide (EPA Reg. No. 59639 - 147) is a water- dispersible granule formulation containing 50% active ingredient (ai). Applications are to be made as broadcast foliar spray s in sufficient water for thorough coverage using ground equipment (including chemigation) or aerial equipment. Depending on the crop and the targeted fungal disease, single application rates range from 0.0625 - 0.125 lb ai/A. Depending on the crop, a maximum of one to four applications can be made with minimum retreatment intervals (RTIs) ranging from 7 to 14 day s except for pecan (interval not specified) and pistachio (2 - 3 week interval); the yearly application rates range from 0.125 to 0.500 lb ai/A. Preharvest intervals (PHI s) range from 14 - 35 day s. Immediate plant - back is allowed for barley , corn, cotton, oat, peanut, rye, so yb ean, sugar beet, triticale, wheat, and those crops listed on the label. A 30 - day plant - back interval (PBI) is required for Brassica leafy vegetables and leafy

vegetables. A 120 - day

PBI appli es to other crops. The proposed uses of metconazole are summarized in Table 3.3 . N N N

C H 3 C H 3 O H Cl N N N

C H 3 C H 3 O H Cl

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**Table 3.3. Summ ary of Proposed Directions for Use of Metconazole.**  Applic. Timing, Ty pe, and Equip. Form

ulation [EPA Reg. No.] Applic.

Rate (lb ai/A) Max.

No. Applic. per Year Max.

Yearly Applic. Rate (lb ai/A) PHI

(days) Use Directions and Limitations 1 **Dried Shelled Pea and Bean, Except Soybean, Subgroup 6C** [Dried cultivars of bean ( Lupinus ); bean (Phaseolus ) (includes field bean, kidney bean, lima bean (dry), navy bean, pinto bean, tepary bean); bean ( Vigna ) (includes adzuki bean, blackeyed pea, catjang, cow pea, crowder pea, moth bean, mung bean, rice bean, southern pea, urd bean); broad bean (dry); chickpea; guar; labl ab bean; lentil; pea (Pisum ) (includes field pea); pigeon pea] Postemergence; Broadcast foliar sprays; Ground or aerial equipment; Chemigation 50% WDG

[59639 - 147] 0.08 -

0.125 2 0.25 21 Apply when conditions favor disease development and prior to infection. A second application may be made at a 7 - to 10 - day interval. Apply in sufficient water to obtain thorough coverage of the plant. Apply with ground equipment in a minimum of 20 gallo ns per acre (GPA) or by air in a minimum of 5 GPA. Two applications may be made sequentially. Use a non - group 3 fungicide in alternation with Metconazole 50 WDG Fungicide. **Rapeseed Subgroup 20A** (Borage; crambe; cuphea; exchium; flax seed; gold of pleasure; hare’s ear mustard; lesquerella; lunaria; meadowfoam; milkweed; mustard seed; oil radish; poppy seed; rapeseed (canola varieties only); sesame; sweet rocket; cultivars, varieties and/or hybrids of these) Broadcast foliar spray during flowering; ground or aerial equipment. 50% WDG

[59639 - 147] 0.0625 -

0.125 1 0.125 35 Make application between 20% and 50% bloom. Apply in sufficient water to obtain thorough coverage of the plant. Apply with ground equipment in 10 - 20 GPA or by **a** ir in a minimum of 5 GPA. **Stone Fruit, Crop Group 12 -**  **12** (Black cherry; capulin; Chinese Jujube; Nanking cherry; sweet cherry; tart cherry; cultivars, varieties and/or hybrids of the se) Broadcast foliar spray; ground or aerial equipment 50% WDG

[59639 - 147] 0.078 -

0.125 3 0.375 14 Timing: For brown rot/blossom blight, green fruit rot/jacket rot, or cherry leaf spot, begin applications at green tip. If conditions are favorable for disease development, make additional applications at full bloom and at petal f all. For fruit brown rot, make applications 14 to 21 days prior to harvest. For powdery

mildew, follow the brow n rot/blossom blight schedule; make additional applications on a 10 - 14 day interval until terminal grow th ceases; application can be made a fter harvest.

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**Table 3.3. Summ ary of Proposed Directions for Use of Metconazole.**  Applic. Timing, Ty pe, and Equip. Form

ulation [EPA Reg. No.] Applic.

Rate (lb ai/A) Max.

No. Applic. per Year Max.

Yearly Applic. Rate (lb ai/A) PHI

(days) Use Directions and Limitations 1 Apply as a foliar spray in sufficient water to obtain thorough coverage of blossoms, foliage, and or fruit. Apply with ground equipment in 100 - 400 GPA or by air in a minimum of 20 GPA. Do not make more than 2 applications after petal fall. **Stone Fruit, Crop Group 12 -**  **12** (Apricot; Japanese apricot; nectarine and peach) Broadcast foliar sprays; ground or aerial equipment 50% WDG

[59639 - 147] 0.078 -

0.125 3 0.375 14 Timing: For brown rot/blossom blight, green fruit rot/jacket rot, scab, or shot hole, begin applications at early pink bud stage before infection occurs. If conditions are favorable for disease development, make additional applications at full bloom and at petal fall. For fruit brown rot, make applications 14 - 21 day s prior to harvest. For powdery

mildew, follow the brow n rot/blossom blight schedule; make additional applications on a 10 - 14 day interval until terminal grow th ceases. Begin applications prior to disease development and continue at a 7 - 10 day interval. For rust, begin application when bud tissue is susceptible to disease development (i.e., pink, white, or red bud). If conditions are favorable for disease development, make a second application at full bl oom or at petal fall. Apply as a foliar spray in sufficient water to obtain thorough coverage of blossoms, foliage, and or fruit. Apply with ground equipment in 100 - 400 GPA or by air in a minimum of 20 GPA.

### Page **14** of **58**

**Table 3.3. Summ ary of Proposed Directions for Use of Metconazole.**  Applic. Timing, Ty pe, and Equip. Form

ulation [EPA Reg. No.] Applic.

Rate (lb ai/A) Max.

No. Applic. per Year Max.

Yearly Applic. Rate (lb ai/A) PHI

(days) Use Directions and Limitations 1 Do not make more than 2 applications after petal fall. **Stone Fruit, Crop Group 12 -**  **12** (American plum; beach plum; Canada plum; cherry plum; Chickasaw plum; Damson plum; Japanese plum; Klamath plum; plum; plumcot ; prune plum; sloe) Broadcast foliar spray; ground or aerial equipment 50% WDG

[59639 - 147] 0.078 -

0.125 3 0.375 14 Timing: For brown rot/blossom blight and rust, begin applications at green tip. If conditions are favorable for disease development, make additional applications at full bloom and at petal fall. For powdery

mildew, follow the brow n rot/blossom blight schedule; make additional applications on a 10 - 14 day interval until terminal grow th ceases. Apply as a foliar spray in sufficient water to obtain thorough coverage of blossoms, foliage, and or fruit. Apply with ground equipment in 100 - 400 GPA or by air in a minimum of 20 GPA. Do not make more than 2 applications after petal fall Do not apply Metconazole 50 WDG Fungicide to “Stanley” type plums.” **Sunflower Subgroup 20B** (Calendula; castor oil plant; Chinese tallowtree; euphorbia; evening primrose; jojoba; niger seed; rose hip; safflower; stokes aster; sunflower; tallowwood; tea oil plant; vernonia; cultivars, varieties, and/or hybrids of these) Postemergence; Broadcast foliar spray; Ground or aerial equipment 50% WDG

[59639 - 147] 0.078 -

0.125 2 0.25 21 Apply when conditions favor disease development and prior to infection. A second application may be made on a 7 - to 14 - day interval. Apply as a foliar spray in sufficient water to obtain thorough coverage of leaves. Apply by ground in a minimum of 20 GPA or by air in a minimum of 5 GPA. Two applications may be made sequentially. Use a non - group 3 fungicide in alternation with Metconazole 50 WDG Fungicide.

### Page **15** of **58**

**Table 3.3. Summ ary of Proposed Directions for Use of Metconazole.**  Applic. Timing, Ty pe, and Equip. Form

ulation [EPA Reg. No.] Applic.

Rate (lb ai/A) Max.

No. Applic. per Year Max.

Yearly Applic. Rate (lb ai/A) PHI

(days) Use Directions and Limitations 1 **Tree Nuts, Crop Group 14 -**  **12, Except Filbert, Pecan, and Pistachio**  (African nut - tree; almond; beechnut; black walnut; Brazil nut; Brazilian pine; bunya; bur oak; butternut; Cajou nut; candlenut; cashew; chestnut; chinquapin; coconut; coquito nut; dika nut; English walnut; ginkgo; Guiana chestnut; heartnut; hickory nut; Japanese horse - chestnut; macadamia nut; mo ngongo nut; monkey -pot; monkey puzzle nut; Okari nut; Pachira nut; peach palm nut; pequi; Pili nut; pine nut; Sapucaia nut; tropical almond; yellowhorn; cultivars, varieties and/or hybrids of th ese) Broadcast foliar spray; Ground or aerial equipment 50% WDG

[59639 - 147] 0.078 -

0.11 4 0.44 25 Begin applications prior to disease development and continue at a 7 to 14 day interval throughout the year. Apply as a foliar spray in sufficient water to obtain thorough coverage of blossoms, foliage and/or fruit. Apply in 100 - 400 GPA with ground equipment or in a minimum of 20 GPA by air. Do not make more than 2 applications after petal fall. **Filbert (Hazelnut)** Broadcast foliar spray; Ground or aerial equipment 50% WDG

[59639 - 147] 0.11 4 0.44 25 Begin applications starting at bud swell to bud break and continue at 10 or 14 - day intervals. Apply as a foliar spray in sufficient water to obtain thorough coverage of all branches. Apply in 100 - 400 GPA with ground equipment or in a minimum of 20 GPA by air. Do not make more than 2 sequential applications before switching to a non - Group 3 fungicide for resistance management. **Pecan** Broadcast foliar spray; Ground or aerial equipment 50% WDG

[59639 - 147] 0.078 -

0.11 4 0.44 25 Begin applications when leaves reach one - half mature size. Continue to make scab applications if scab model predicts need. Apply as a foliar spray in sufficient water to obtain thorough coverage of blossoms, foliage and/or fruit.

### Page **16** of **58**

**Table 3.3. Summ ary of Proposed Directions for Use of Metconazole.**  Applic. Timing, Ty pe, and Equip. Form

ulation [EPA Reg. No.] Applic.

Rate (lb ai/A) Max.

No. Applic. per Year Max.

Yearly Applic. Rate (lb ai/A) PHI

(days) Use Directions and Limitations 1 Apply in 100 - 400 GPA with ground equipment or in a minimum of 20 GPA by air. Do not make more than 2 sequential applications before switching to a non - Group 3 fungicide for resistance management. **Pistachio** Broadcast foliar spray; Ground or aerial equipment 50% WDG

[59639 - 147] 0.125 4 0.500 25 Apply prior to onset of disease development and continue on a 2 to 3 week interval. Apply as a foliar spray in sufficient water to obtain thorough coverage of blossoms, foliage and/or fruit. Apply in 100 - 400 GPA with ground equipment or in a minimum of 20 GPA by air. Do not make more than 2 sequential applications before switching to a non - Group 3 fungicide for resistance management. 1 **Rotational Crop Restrictions** : Immediate plant -back is allowed for barley, corn, cotton, oat, peanut, rye, soybean, sugar beet, triticale, wheat, and those crops listed on the label. A 30 - day plant -back interval is required for Brassica Leafy Vegetables and Leafy Vegetables. Do not plant any crop, except barley, corn, cotton, oat, peanut, rye, soybean, sugar beet, triticale, wheat, Brassica Leafy Vegetables, Leafy Vegetables and those crops listed on the label, earlier than 120 days after applying Metconazole 50 WDG Fungicide.

### Page **17** of **58**

**3.4 Anticipated**  **Exposure Pathways** Humans may

be exposed to metconazole in food and drinking water, since metconazole may be applied directl y to growing crops and application may result in metconazole reaching surface and ground water drinking water sources . There are e xisting residential uses of metconazole so there is exposure to residential handlers and those entering treated areas following application. In occupational settings, applicators may be exposed while handling metconazole . There is a potential for post - application exposure for workers re - entering treated fields and residents re entering treated areas . Risk assessments have been completed for proposed and existing uses of metconazole . This risk assessment considers all of the aforementioned exposure pathway s based on the proposed new uses of metconazole , but also considers existing uses of metconazole , particularly in the dietary and residential exposure assessment s . **3.5 Consideration of Environmental Justice**  Potential areas of environmental j ustice 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 L ow - 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 U.S. Department of Agriculture’s National Health and Nutrition Examination Survey , What We Eat in America, (NHANES/WWEIA) and are used in pesticide risk assessments for all registere d food uses of a pesticide. These data are anal yz ed and categorized by subgroups based on age and ethnic group. Additionally , OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, non - dietary

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 post - application are evaluat ed. Further considerations are currentl y in development as OPP has committed resources and expertise to the development of specialized software and models that consider exposure to b ys tanders and farm workers as well as lifestyl e and traditional dietary p atterns among specific subgroups. **4.0 Hazard Characterization and Dose**  **- Response Assessment**  Th ese section s are based on the h azard c haracterization derived from previous risk assessments: D 350369, B. O’Keefe, 10/20/08; D386421, B. O’Keefe , 09/30/2011.

### Page **18** of **58**

**4.1 S**  **ummary of Toxicological Effects** Metconazole is a member of the triazole class of systemic fungicides which acts primaril y as an inhibitor of ergosterol biosy nthesis. The proposed mode of action for metconazole is via inhibition of sterol (ergostero l) biosy nthesis in fungi which is consistent with altered cholesterol levels observed in mice and rats. Overall, metconazole appears to affect the liver, kidney , spleen, and various blood parameters in all the species tested. Dose levels at which these effects occur are similar across species. 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 expos ure durations. While liver effects , including changes in liver weight and enzy me activity , have been reported consistently across multiple exposure durations and species, these effects were considered slight or minimal in some studies and appeared to be " adaptive" responses. However, based on the weight of evidence from the consistency of these reported effects and evidence that these effects increase in severity with exposure duration , leading to liver tumors in the chronic mouse study , they were considered "adverse" and formed the basis of the study L OAELs. Metconazole is considered non - genotoxic 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 ( see section 4. 3.3 ) . The established chronic RfD would be protective of mitogenesis/carcinogenesis. Other major critical effects observed in oral studies were decreased body weight and blood effects (reductions in erythrocy te and/or platelet parameters) in the mouse, rat, dog and/or rabbit. Splenic effects including increased spleen weight and hy perplasia were observed in the mouse, rat and dog at dose levels where liver effects were also observed. In dogs, lenticular degeneration (cataracts) was observed at the highest dose tested (114 mg/kg/day). Furthermore, at high dietary

levels, there is evidence that metconazole is a gastrointestinal irritant in the dog. Developmental studies in rats and rabbits show evidence of developmental effects such as skeletal anomalies, fetal death (resorptions, post - implantation loss, decreased viability indices) and malformations including hydrocephal y . There was no quantitative or qualitative susceptibility

to the fetuses of rabbits following in utero exposure to metconazole . Inthe two available prenatal developmental toxicity studies in rabbits, developmental effects (increased post - implantation loss and reduced fetal body weights) were observed at the same dose that caused maternal toxicity

(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 offsprin g) was observed only at the highest tested dose, a dose which also resulted in parental toxicity as evidenced b y reduced parental body weight, increased incidence of fatty hepatocy te changes in male parental animals and increased incidence of spleen conges tion in F1 parental females. In one developmental study in rats, no susceptibility

was shown. However, in a second ratdevelopmental toxicity study , skeletal variations (predominantly lumbar ribs) occurred at the L OAEL in the absence of maternal toxicity, and more severe effects such as increased incidence of post - implantation loss, hydrocephal y and visceral anomaliea (cranial hemorrhage, dilated renal pelvis, dilated ureters,

### Page **19** of **58**

and displaced testis were reported at the next higher dose, again in the absence of maternal toxicity . While quantitative susceptibility is demonstrated in th is study , it was not duplicated in the other rat developmental study , the two rabbit developmental studies or the multi - generation reproduction study. Furthermore, the endpoint and point of departure for risk assessment are based on the developmental effects seen in the fetus, for which there is a clear NOAEL. Therefore, it is concluded that there is low concern and no residual uncertainty for pre - and/or post - natal toxicity . Metconazole did not demonstrate neurotoxicity in the available subchronic neurotoxicity study . In formation available from the 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 do not indicate any neurotoxic signs. 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. Therefore, the requirement for an acute neurotoxicity study has been waived (TXR0056405, K. Rury , 08/09/2012). Toxicity via the inhalation route has not been evaluated because the data requirement for a route specific subchronic inhalation study has no t been met and remains outstanding (TXR0057053 , J. Leshin , 10/09/2014 ). 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 **absorption, distribution, metabolism and excretion** of metconazole were investigated in rats following single oral doses of cis and or cis/trans metconazole radiolabeled at the cyclopentylor triazole ring ( cis only). M etconazole was significantl y absorbed, with the time to maximum plasma concentration s for male and female rats treated with either the low - or high dose occurring with 4hr . The plasma half - life of low - and high - dose rats was slightly shorter in males than females, ~20 - 25 hours and ~34 hours, respectivel y. Plasma pharmacokinetic studies showed a low potential for bioaccumulation following single or multiple dosing regimen s . Relatively

higher concentrations were found in the gastrointestinal tract, adrenals and liver. The pattern of metabolites was similar at the low and high dose. Metconazole metabolites consist primarily

of mono - and pol y- hydrox yl ated derivatives of the parent molecule. Hydroxylation occurs mainly on the alkylconstituents of the phenyland cyclopentyl rings. Sulfate conjugation to the cyclopentylring hydrox ylgroups was also identified. Monohydroxy metabolites were found in the feces and di - and tri - hydroxy compounds were found more often in the urine. Initial studies showed less than 2% of th e dose was expired in the air. Excretion was primaril y via feces (80% male, 67% female) with biliary excretion being the prominent route of elimination with the urine being the secondary route . B y 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.

### Page **20** of **58**

The **dermal absorption** factor is 16% based on the results of an in vivo dermal absorption study (MRID 46808450 ) . **4. 2**  **Safety Factor for Infants and Children (FQPA Safety Factor)** The toxicity

database is considered complete and adequate for risk assessment. There was no evidence of neurotoxicity in the database; there is low or no concern for developmental or reproductive toxicity , and for susceptibility in the developing or young animal. There are no residual uncertainties identified in the exposure databases. Therefore, the FQPA Safety Factor has been reduced to 1 X . **4.2.1 Completeness of the Toxicology Databas**  **e** The toxicity

database is considered complete and adequate for risk assessment, with the exception of a subchronic inhalation study . All studies needed to assess susceptibility concerns, such as developmental and reproduction studies, have been submitte d. Additional studies needed to assess neurotoxicity

are also available. A s ubchronic inhalation study is required because the use of an oral point of departure (POD) results in MOEs as low as 380 for occupational exposure with the current proposed use , which the Hazard and Science Policy Council has determined is not sufficient to alleviate concern (TXR0057053 . J. L eshin . 10/09/2014). Therefore, a 10 X database uncertainty

factor has been added for inhalation exposure. **4.2.2 Evidence of Neurotoxicity**  In accordance with the revised 40 CFR Part 158 data requirements, an acute and subchronic neurotoxicity

battery is required for this risk assessment. However, requirement for an acute neurotoxicity

study has been waived (TXR0056405, K. Rury , 08/09/2012), and an acceptable subchronic neurotoxicity

study showed no neurotoxic effects at levels that produced s ys temic toxicity in the study , as well as in other subchronic and chronic studies. **4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or**  **Young Animal** As discussed in section 4.1, the toxicity database contains five relevant guideline studies: two developmental studies in the rat, two developmental studies in the rabbit, and one multigeneration reproduction study . There was evidence of quantitative susceptibility in one developmental rat study, but not in the four other studies. C oncern is for susceptibility low since susceptibility

was not corroborated b y the other studies ; concern is low also because the NOAELs are well defined, and the dose/endpoint is used for acute dietary risk assessment for the sensitive population. **4.2.4 Residual Uncertainty in the Exposure Database**  Dietary exposure assessments were conducted using tolerance - level residues and assumed 100% crop treated. Therefore, the acute and chronic dietary (food onl y) 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

### Page **21** of **58**

underestimate actual exposure. The drinking water component of the dietary assessment utilizes water concentrati on values generated b y model and associated modeling parameters which are designed to provide conservative, health protective, high - end estimates of water concentrations which will not likely

be exceeded. While there is potential for post - application resi dential exposure, the best data and approaches currentl y 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 because the ass essment was a screening level assessment. **4.3 Toxic**  **ity Endpoint and Point of Departure Selections 4.3.1**  **Dose -**  **Response Assessment** The endpoints and points of departure (POD) for this risk assessment are based on those of a previous risk assessment. The rationales for each selection, along with a detailed description of the toxicity

studies used for various exposure scenarios are presented in that risk assessment document (D308794. B. O’Keefe . 07/06/2006). Following is a summary : **Acute dietary endpoints** : There was no appropriate single - dose endpoint identified for acute oral exposure of the general population to metconazole. For the Females aged 13

– 49 population group, the POD of 12 mg/kg bw/day was established from the NOAEL of a developmental toxici ty

study , based on the increased incidence of skeletal anomalies including extra lumbar ribs, cervical ribs and extra pre - sacral vertebra at the LOAEL of 30 mg/kg/day . While these skeletal anomalies are not usuall y considered single dose effects, they are used as the basis for an acute endpoint in this case because more severe, single - dose effects occur at the next higher dose level (75 mg/kg/day) such as increased incidence of post - implantation loss, hydrocephal y and visceral anomaliea (cranial hemorrhage , dilated renal pelvis, dilated ureters, and displaced testis . **Chronic dietary endpoint** : HED selected the NOAEL of 4.3 mg/kg/day from a two - ye ar chronic study in the rat for establishing the chronic RfD, based increased spleen and liver weights and incre ased hepatocellular vacuolation and hy pertrophy at the LOAEL of 13.1 mg/kg bw/day . These effects at the L OAEL are part of a dose - related progression of toxicity seen in this study, which includes adverse hematology and clinical chemistry

changes as well a s histopathological changes such as increased incidence of eosinophilic and clear- cell hepatocellular foci at the next higher dose level. Other studies such as the 28 - day , 90 - day , and subchronic neurotoxicity

studies all confirm the chronic NOAEL of 4.3 mg/kg/day , with NOAELs of 9.1, 6.4, and 4.8 mg/kg/day , respectively , based collectively on decreased body weight, increased liver, kidney and spleen weights, hepatocellular hyp ertrophy and vacuolation at the LOAELs of 15.7 mg/kg/day and above. Therefore, the NOAEL of 4.3 mg/kg/day is considered the appropriate POD for this exposure scenario. For **short -**  **term incidental oral** exposure the POD of 9.1 mg/kg/day was selected from the NOAEL of a 28 - day

oral study

in rats, with a NOAELof 9.1 mg/kg/day and a LOAEL of 90.5

### Page **22** of **58**

mg/kg/day), based on decreased body weight, increased liver and kidney weights, hepatocellular vacuolation and hypertrophy . This study was selected because (1) endpoints identified were observed at the appropriate duration of exposure (1 - 30 day s) and (2) the route of exposure (oral) and populations and endpoints are appropriate for the populations of concern including adults, infants and children (this POD is protective of the developmental effects seen in the rat). **The intermediate -**  **term incidental oral endpoint** was selected from the 90 - day subchronic study in rats. The NOAEL for this study is 6.4 mg/kg/day

and the LOAEL is 19.2 mg/kg/day based on increased hepatocellular fatty vacuolation and increased spleen weight in females. This study was selected because (1) endpoints identified were observed at the appropriate duration of exposure (1 - 6 months) and (2) the ro ute of exposure (oral) and endpoints are appropriate for the populations of concern including adults, infants and children (this POD is protective of the developmental effects seen in the rat). **Short -**  **and Intermediate -**  **Term dermal endpoints** were not selec ted because quantification of dermal risk is not required. No sy stemic or dermal toxicity was seen at the l imit dose in a 21 - day dermal toxicity

study in the rat . There are no neurotoxicity, developmental or reproductive issues which would raise concern f or these toxicities , which are not looked for in the 21 - day dermal study . Also, the DAF is established at 16% which suggests that any toxicities seen in the developmental, reproduction and neurotoxicity studies via the oral route, would be expected to be s een at a significantl y higher dose level via the dermal exposure route. Hence the dermal risk quantification is not required. **For Short -**  **term inhalation exposures** , the POD of 9.1 mg/kg/day (no observed adverse effect level (NOAE L)) is based on an oral 28 - day rat toxicity

study . In the study , the effects observed at the lowest observed adverse effect level (LOAEL) were decreased body weight (males ), increased liver and kidney weight and hepatocellular hy pertrophy and vacuolation (males and females ). In th e absence of repeated exposure inhalation toxicity studies, an oral study

for this population subgroup was selected and a 10X database uncertainty factor was added. **For intermediate -**  **term inhalation exposures** , the POD of 6.4 mg/kg/day (NOAEL) is based on an oral 90 - day

rat toxicity

study . In the study, the effects observed at the LOAEL were increased spleen w eight ( females ) and hepatic vacuolation ( males ). In the absence of repeated exposure inhalation toxicity

studies, an oral study

for this population subgroup was selected and a 10X database uncertainty

factor was added. **4.3.2 Recommendation for Combining Routes of Exposure for Risk Assessment**  When there are potential residential exposures to a pesticide, aggregate risk assessment must consider exposures from three major sources: oral, dermal and inhalation exposures. 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 long - term dermal or inhalation exposures to metconazole under the current uses .

### Page **23** of **58**

**4.3.3 Cancer Classification and Risk Assessment Recommendation**  The Cancer Assessment Review Committee (CARC) Classification is: “Not Likel y 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 likel y below a defined dose that doesn’t cause mitogenesis based on bioassay s in the rat and the mouse, combined with a lack of in vitro or in vivo mutagenicity (TXR# 005 4211, J. Kidwell, 4/14/06). No quantification is required. **4.3.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk**  **Assessment Table**  **4.3.4.1 . Summ**  **ary of Toxicological Doses and Endpoints for Metconazole for Use in Dietary and Non**   ** Occupational Hum** **an Health Risk Assessments Exposure/**  **Scenario Point of** 

**Departure Uncertainty/FQPA** 

**Safety Factors RfD, PAD, Level** 

**of Concern for Risk Assessment**  **Study and Toxicological Effects** Ac ute 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 revie wed.
Ac ute Dietary (Females 13 - 49 years of age) NOAEL= 12

mg/kg/day UF A= 10 X

UF H= 10 X FQPA SF= 1 X Ac ute RfD = 0.12

mg/kg/day aPAD= 0.12 mg/kg/day **Developm ental toxicity in rats:** 

LOAEL = 30 mg/kg/day based on increases in skeletal variations. At 75 mg/kg/day (the next higher dose level) increased incidence of post im plantation loss, hydrocephaly and visceral anomaliea (cranial hemorrhage, dilated renal pelvis, dilated ureters, and displaced testis) were reported. Chronic Dietary (All Populations) NOAEL= 4.3

mg/kg/day UF A=10 X

UF H= 10 X FQPA SF= 1 X 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 increas ed spleen weight. Incidental Oral Short - Term

(1 - 30 days) NOAEL= 9.1

mg/kg/day UF A= 10 X

UF H=10 X FQPA SF= 1 X 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 Intermediate Term (1 - 6 mo nths) NOAEL= 6.4

mg/kg/day UF A= 10 X

UF H=10 X FQPA SF= 1 X 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).

### Page **24** of **58**

**Table 4.3.4.1**  **. Summ ary of Toxicological Doses and Endpoints for Metconazole for Use in Dietary and Non**  **** **Occupational Hum an Health Risk Assessments**  **Exposure/ Scenario**  **Point of**

**Departure Uncertainty/FQPA** 

**Safety Factors RfD, PAD, Level** 

**of Concern for Risk Assessment**  **Study and Toxicological Effects** Dermal Short - (1 - 30 days) & Intermediate Term (1 - 6 mo nths) Quantification of dermal risk is not required due to lack of syst emic or dermal toxicity at the Limit

Dose in a 21 - day

dermal toxicity study in the rat, the lack of neurotoxicity, and the lack of developmental and/or reproductive toxicity in the absence of parental effects , which were not looked for in the dermal toxicity. Inhalation Short - Term (1 - 30 days) NOAEL= 9.1

mg/kg/day UF A= 10 X

UF H=10 X UF DB =10X FQPA SF= 1 X Residential LOC

for MOE = 100 0 **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 Intermediate Term (1 - 6 mo nths) NOAEL= 6.4

mg/kg/day UF A= 10 X

UF H=10 X UF DB =10X FQPA SF= 1 X Residential LOC

for MOE = 100 0 **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. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF DB = to account for the absence of key dat a (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. **Table 4.3.4.2**  **. Summ ary of Toxi**  **cological 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) & Intermediate Term (1 - 6 mo nths) 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, the lack of target organ toxicity or neurotoxicity, and the lack of dev elopmental and/or reproductive toxicity in the absence of parental effects which were not looked for in the dermal toxicity. Inhalation Short - Term

(1 - 30 days) NOAEL=9.1

mg/kg/day UF A= 10 X

UF H=10 X UF DB =10X Occupational LOC

for MOE = 100 0 **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 Intermediate term (1 - 6 mo nths) NOAEL=6.4

mg/kg/day UF A= 10 X

UF H=10 X UF DB =10X Occupational LOC

for MOE = 100 0 **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 **25** of **58**

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 obs erved adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (int erspecies). UF H = potential variation in sensitivity among members of the human population (intra species). UF DB = 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. 

### 5.0 **Dietary Exposure and Risk Assessment 5.1**  **Residues of Concern Summary and Rationale** The nature of the residue in crops is adequatel y understood based on metabolism studies on banana, canola, mandarin, pea, and wheat. The metabolism of metconazole was similar in all crops investigated. Metconazole (parent) is the residue of concern for the tolerance expression for primary

and rotational crops. Metconazole is the residue of concern for risk assessment purposes in primary

and rotational crops except for cereal grains; the residues of concern for risk assessment in cereal grains (as both primary and rotational crops) are metconazole and the metabolite M11. HED also has concern for residues of 1,2,4 - triazole, TA, and TAA in plants as a result of the use of metconazole. However, because separate endpoints for these compounds have been established, exp osure and risks from free triazole and its conjugates will be addressed separatel y. The nature of the residue in livestock (ruminants and poultry) is adequatel y understood. The residue of concern for the tolerance expression in livestock commodities is m etconazole . The residues of concern in livestock for purposes of the risk assessment are metconazole and metabolites M1 (free and its glucuronic acid conjugate), M12, and M31 (free and its glucuronic acid conjugate). HED also has concern for residues of 1,2,4 - triazole, TA, and TAA in livestock as a result of the use of metconazole. However, because separate endpoints for these compounds have been established, exposure and risks from free triazole and its conjugates will be addressed separatel y. For drinking water, the resid u e of concern for metconazole is the parent only . **Table 5.1. Summ ary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance**  **Expression .**  **Matrix Residues Included In Risk**  **Assessment a**  **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 Ruminant Metconazole; M1 and its glucuronic acid conjugate; M12; M31 and its glucuronic acid conjugate Metconazole Poultry Drinking Water Metconazole Not Applicable

### Page **26** of **58**

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 variou s parent compounds, risks associated with exposure to 1,2,4 - T and to TA/TAA are addressed in separate risk assessment documents.

a M1 = 5 - [(4 - chlorophenyl)methyl] - 2 - me thoxyl - 2 - me thyl - 1 - (1 H - 1,2,4 - triazol - 1 - ylmethyl) - 1 - cyclopentanol; M11 = 5 - [(4 - chlorophenyl)methoxyl] - 2,2 - dimethyl - 1 - (1 H - 1,2,4 - triazol - 1 - ylmethyl) - 1 - cyclopentanol; M12 = 5 - [(4 - chlorophenyl)methyl] - 2 - carboxyl - 2 - me thyl - 1 - (1 H - 1,2,4 - triazol - 1 - ylmethyl) - 1 - cyclopentanol; M31 = (1S*,3R*,5S*) - 3 - hydroxy - cis - metconazole; 1,2,4 - T = 1 H - 1,2,4 - triazole; TAA = 1 H - 1,2,4 - triazol - 1 - yl acetic acid; TA = 2 - amino - 3 - (1 H

- 1,2,4 - triazol - 1 - yl)propanoic acid. 

### 5 **.2 Food**  **Residue Profile**  IR - 4 submitted field trial data on dry bean (MRID 4 9297801 ), dry pea (MRID 4 92978 02), and sunflower (MRID 4 9297803 ). The data reflect th e proposed use patterns. The number of trials and geographic distribution are acceptable. The analy tical method used is adequate for determination of the residue of concern, and the samples were stored frozen for intervals supported by

the storage stabil ity

results. A summary

of the residue data from the crop field trials is presented in Appendix F, Table s F.1 through F . 5 . The existing field trial data for the crop group conversions are adequate. The previousl y submitted field trial data on canola, cherry , peach, plum, almond, and pecan are adequate to support the rapeseed subgroup 20A, the stone fruit subgroup 12 - 12, and the tree nut group 14 - 12. The number of field trials and geographic representations are adequate. Adequate storage stability

dat a are available to support the field trial data. An adequate data collection method, the GC/NPD method RM - 41C - 1, was used to determine metconazole ( cis - and trans isomers) in canola, stone fruit, and tree nuts. Residues of 1,2,4 - triazole, TA, and TAA were determined in canola seed using an adequate LC /MS/MS method (Morse Laboratories Method 160). Although stone fruit and tree nut samples were not analyzed for the triazole metabolites, field trial data for triazoles are not required for those petitions submitted in 2006. Processed Food and Feed Adequate processing studies have been submitted on canola, plum, and sunflower. Canola: Metconazole (the sum of cis - and trans - isomers) was non - detectable in/on canola seed, meal and refined oil samples reflecting treatment at a 5x rate; therefore, separate tolerances are not required for canola meal and oil. Residues of 1,2,4 - triazole were also not detectable in canola seed, meal and refined oil reflecting treatment at 5 X . Residues of TA and TAA do not concentrate in oil. However, residues of TA and TAA concentrated in canola meal b y 2.1 X and 1.4 X , respectively . Plum: Metconazole (the sum of cis - and trans - isomers) concentrates 2.3 X in prunes. Sunflower: M etconazole (the sum of cis - and trans - isomers) does not concentrate in sunflower meal and oil. Residues of TA concentrate 2.9 X in sunflower meal, but do not concentrate in oil.

### Page **27** of **58**

Livestock Adequate cattle and poultry feeding studies were previously submitted and reviewed. Based on the cattle f

eeding study

and the calculated dietary burden based on the maximum reasonabl y balanced diet ( Table 1 Feedstuffs , June 2008), no changes are required in the established livestock tolerances as a result of the proposed/expanded uses. The established tolera nces for meat by products of cattle, goat, horse, and sheep at 0.04 ppm and for egg at 0.04 ppm are adequate. No tolerances are established for milk; fat and meat of cattle, goat, hog, horse, poultry , and sheep; or meat b yproducts of hog and poultry since residues are not expected to occur in those commodities. I f additional uses increase the dairy cattle dietary

burden, additional ruminant feeding studies conducted at higher rates may be needed. Rotational Crops Adequate limited field rotational crop studies have previously been submitted. Based on the limited field rotational crop trials, rotational crop restrictions are included on the registered Metconazole 50 WDG label (EPA Reg. No. 59639 - 147). The same rotational crop restrictions on the propose d Metconazole 50 WDG label are adequate. **5.3 Water Residue Profile**  The drinking water residues used in the dietary risk assessment were provided EFED (D418674, F . Khan, 9/30/20 14) and incorporated directl y into this dietary assessment in the DEEM - FCID into the food categories “water, direct, all sources” and “w ater, indirect, all sources.” Parent m etconazole is the only residue of concern considered in the drinking water assessment. HED determined that degradates of metconazole were not to be included ( Residues of Concern Knowledgebase Subcommittee (ROCKS) , USEPA, 2008, D348234 ). For surface water, the Surface Water Concentration Calculator (SWCC v 1.106) model was used to generate EDWCs for the Tier II aquatic exposure assessment based on cranberry u se. The SWCC is a graphical user interface that runs the Pesticide Root Zone Model (PRZM, v 5, November 15, 2006) and the Variable Volume Water Body Model (VVWM, 3/6/2014) (USEPA, 2006b). The default percent cropped area (PCA) factor of 1.0 was used. For peak exposure and annual mean exposure, lower EDWCs for surface water were generated using the Tier II Pesticide Root Zone Model and Exposure Analy sis Modeling Sy stem (PRZM EXAMS), based on metconazole use on PA turf with a PCA factor of 1. The use on tu rf reflected the highest application rate (i.e., five applications at 0.6 lb ai/A/application with a 14 - day retreatment interval). The modeled EDWCs for pea/bean (dried shelled) and sunflower did not exceed the concentrations from PA turf. For ground water, the PRZM - Ground Water (PRZM - GW) model was used to estimate EDWCs. The highest application rate, which was the application rate for turf, was modeled in estimating metconazole EDWCs for ground water. Since application rates for proposed uses are lower than turf, no additional PRZM - GW modeling was conducted. The EDWCs used in HED’s human health dietary risk assessment are bolded in summary Table 5.3.1 below. The ground water EDWC of 51.8 μ g/L(ppb) was used in the acute dietary

### Page **28** of **58**

assessment. The surface water EDWC of 43.9 μ g/L (ppb) was used in the chronic dietary assessment. The drinking water models and their descriptions are available at the EPA internet site: http://www.epa.gov/oppefed1/models /water/ . **Table 5.3.1. Recommended EDWCs for the Proposed Uses of Metconazole for Drinking Water Sources**  1 **Drinking Water Source**  **Crop Scenario (Model)** 

### Peak **Exposure (Acute)**  **(μg/L)** 

### Annual Mean

**Exposure (Non**  **- Cancer**  **Chronic) (μg/L)**  **30 -**  **year Mean**

**Exposure (Cancer**  **Chronic) (μg/L)**  Surface Water Turf 2 45.5 31.3 22.8

Cranberry3 49.6 **43.9** NA 5 Ground water WI Central Sand Scenario 4 **51.8** NA 5 20.0 1 Bolded values are the recommended EDWCs for assessing acute and chronic dietary exposures from metconazole uses. 2 The Tier II model PRZM/EXAMS was used to generate EDWCs for surface water, based on metconazole use on PA turf. A percent cropped area (PCA) factor of 1 was used. 3 The SWCC v 1.106 model was used to generate EDWCs for the Tier II aquatic exposure assessment. The SWCC is a graphical user interface that runs the Pesticide Root Zone Model (PRZM, v 5, November 15, 2006) and the Variable Volume W ater Body Model (VVWM, 3/6/2014) (USEPA, 2006b). The default PCA factor of 1.0 was used. 4 The Tier 1 PRZM - GW model was used to reassess ground water EDWCs for the turf use, which has the highest application rate (5 applications at of 0.6 lbs ai/A/application). 5 Not applicable. 

### 5.4 **Dietary Risk Assessment 5.4.1**  **Description of Residue Data Used in Dietary Assessment** The dietary

exposure analy sis incorporates all current and proposed tolerances for residues of metconazole , including its metabolites and degradates. An unrefined acute dietary (food and drinking water) exposure assessment was conducted. The residue levels used in the assessment were the established or recommended tolerance levels except for cereal grains and livestock commodities. Since cereal grains and livestock commodities include metabolites as residues of concern in the risk assessment, maximum residue values for the metabolites from field trials were added to the metconazole tolerance levels. DEEM default processing factors or empirical processing factors were used, as available. Itwas assumed that 100% of the crops were treated. The EDWC used in the acute dietary assessment was provided by the EFED and incorporated directl y into the acute asse ssment. The ground water EDWC of 51.8 μ g/L (ppb) generated b y the PRZM - GW model was used in the acute dietary assessment. The highest application rate, which was the application rate for turf, was modeled using the WI Central Sand Scenario in estimating metconazole EDWCs for ground water.

### Page **29** of **58**

An unrefined chronic dietary (food and drinking water) exposure assessment was conducted. The residue levels used in the assessment were the established or recommended tolerance levels except for cereal grains and livestock commodities. Since cereal grains and livestock commodities include metabolites as residues of concern in the risk assessment, maximum residue values for the metabolites from field trials were added to the metconazole tolerance levels. DEEM default processing factors or empirical processing factors were used, as available. It was assumed that 100% of the crops were treated. The EDWC used in the chronic dietary assessment was provided by EFED and incorporated directl y into the chronic assessment. The surface water EDWC of 43.9 μ g/L (ppb) generated b y the SWCC model was used in the chronic dietary assessment. The SWCC model was used to generate EDWCs for the Tier II aquatic exposure assessment ba sed on the cranberry scenario. Metconazole is classified as “not likely to be carcinogenic to humans” . Therefore, a cancer dietary exposure assessment was not conducted. **5.4.2 Perc**  **ent Crop Treated Used in Dietary Assessment** It was assumed that 100% of the crops were treated for all commodities . **5.4.3 Acute Dietary Risk Assessment**  For the general U.S. population , including infants and children , an appropriate dose/endpoint attrib utable to a single dose was not observed in the available oral toxicity studies. The acute dietary (food and drinking water) exposure to metconazole is below HED’s level of concern for females 13 - 49 years old, the only population subgroup of concern . F or females 13 - 49 years old , the acute dietary

exposure estimate at the 95 th 

### percentile utilized 4.6 % of the acute population adjusted dose ( aPAD ) , and is not of concern. **5.4.4 Chronic Dietary Risk Assessment**  **s** The chronic dietary

(food and 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 estimates utilize 6. 6% of the chronic population adjusted dose ( cPAD ) for the general U.S. population and 14 % of the cPAD for children 1 - 2 years old , the most highl y exposed population subgroup. **5.4. 5**  **Summary Table Table 5.4.5. Summary of Dietary**  **(Food and Drinking Water) Exposure and Risk for Metconazole.**  **Population Subgroup Acute Dietary**  **(95 th**  **Percentile) Chronic Dietary**  **Dietary Exposure (m**  **g/kg/day) % aPAD** * **Dietary Exposure (m**  **g/kg/day) % cPAD** * General U.S. Population NA NA 0.002653 6.6 All Infants (<1 year old) 0.004963 12 **Children 1 -**  **2 years old*** **0.005391 14** 

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**Table 5.4.5. Summary of Dietary (Food and Drinking Water)**  **Exposure and Risk for Metconazole. Population Subgroup**  **Acute Dietary (95**  **th Percentile)**  **Chronic Dietary Dietary Exposure**  **(m g/kg/day)**  **% aPAD*** **Dietary Exposure (m**  **g/kg/day) % cPAD** * Children 3 - 5 years old 0.004749 12 Children 6 - 12 years old 0.003241 8.1 Youth 13 - 19 years old 0.002045 5.1 Adults 20 - 49 years old 0.002549 6.4 Adults 50 - 99 years old 0.002166 5.4 **Fem ales 13**  **- 49 years old**  * **0.005500 4.6**  0.002179 5.4 *T he subpopulations with the highest risk estimates are bolded. NA = not applicable . 

### 5.4. **6 Dietary Assessment of Free Triazole and its Conjugates**  The proposed new uses of metconazole did not result in an increase in dietary exposure estimates for free triazole or conjugated triazoles. Therefore, the last dietary exposure anal ys es for the triazole metabolites (D414951, T. Morton, 10/24/20 13) did not need to be updated. The past assessment will still adequately cover these uses. **6.0 Residential (Non**  **- Occupa**  **tional) Exposure/Risk Characterization** No new residential uses are being proposed at this time. However, there are existing uses of metconazole on turf and ornamentals in residential settings that have been reassessed in this document to reflect HED’s 2012 Residential SOPs 2 

### along with policy changes for body weight assumptions. Because dermal toxicity endpoints for the appropriate duration of exposure (short term) were not identified up to the limit dose, only residential handler inhalation exposures/risks for adults, and residential post - application incidental oral exposures/risks for children have been assessed. **6.1 Residential Handler Exposure**  Summaries of the short - term inhalation risk estimates for residential handlers are included in Appendix D , Table D.1 . The maximum application rate for each exposure scenario is presented as the worst case scenario. All inhalation risk estimates are greater than the LOC of 1,000; and therefore are not of concern (MOEs range from 6,300 to 23,000,000). Dermal handler risk assessments were not conducted because an adverse s ys temic dermal hazard was not identified for metconazole. **6.2 Post**  **- Application Exposure**  Summaries of the short - term post - application incidental oral risk estimates for children 1 to <2 ye ars old are included in Appendix D, Table D .2. The maximum application rate for each exposure scenario is presented as the worst - case scenario. All incidental oral risk estimates are

2 Available: http://www.epa.gov/pesticides/science/residential - exposure - sop.html

### Page **31** of **58**

greater than the LOC of 100; and therefore are not of concern (MOEs range from 1,000 to 450,000). Dermal post - application risk assessments were not conducted because an adverse sy stemic dermal hazard was not identified for metconazole. Guideline 875.2100 - Turf Transferable Residues (TTR) In accordance with 40CFR158, TTR data are required for all occupational (e.g., sod farms, golf courses, parks, and recreational areas) or residential turf uses that could result in post - application exposure to turf. In the absence of chemical - specific TTR data, EPA uses default values. The 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment includes an anal ys is of all TTR data, available at the time, which resulted in the selection of revised liquid and granular default values for the fraction of the application rate available for transfer after a turf application (F AR

### ). These values are based on an anal ys is of 59 TTR studies performed with the Modified California Roller Method (36 studies using liquids, 11 studies using wettable powders/water dispersible granule s, and 12 studies using granules). The liquid results (N=131) indicate a range of F AR 

### values from 0.0005% to 6.1% and the granular results (N=37) indicate a range of 0.00064% to 0.69%. In both the liquid and granular data, a large range of transferability is observed and this variability can potentiall y be attributable to many factors such as active ingredient; formulation; field conditions in the studies; weather conditions (e.g. humidity); or many other difficult to quantify factors. Although witnessed across multiple chemicals, this range in F AR 

### values is not expected when considering TTR data for a single chemical. HED selected 1% and 0.2% as high - end default values for liquid and granular products, respectivel y. Because TTR data are not available f or metconazole, EPA is using the default value of the currentl y registered residential products. Although there may be a small degree of uncertainty in the use of the default TTR value for metconazole (i.e. , there is a small chance that the F AR 

### value may exceed the applicable default value ), it is likely that the health - protective aspects of EPA’s residential post - application turf assessment methodology will more than compensate for this potential uncertainty (i.e. the methodology is likely to overestimate exposure by a factor greater than the factor than the highest measured F AR 

### values exceed the defaults ). For example, when assessing residential post - application turf exposure, EPA assumes the following: exposures occur to zero - day

(i.e. , day of applicati on ) residues every day of the assessed exposure duration (i.e. , EPA assumes that no dissipation or degradation occurs, it doesn’t rain, the grass is not mowed, etc); individuals perform the same post - application activities performed in the turf transfer c oefficient study

day after day (e.g. tumbling, playing on turf with toy s, etc.); and individuals engage in these post - application activities for a high - end amount of time every day that is represented b y data reflecting time children spend outdoors and not specifically engaged in activities on turf, when in actuality children do not spend all of their outdoor time on turf and high - end levels of activity will not occur every

day . Given the conservatisms discussed above and the potential compounding nature of these conservatisms, EPA is able to rely upon the calculated exposure estimates with confidence that exposure is not being underestimated. Since the estimated residential turf post - application exposure for residential turf using default TTR values for metconazole is minimal in comparison to the level of concern (i.e., the calculated MOE is greater than 10 times higher than the level of concern, MOE = 1,000 compared to the LOC of 100); EPA is waiving the 40 CFR TTR data requirement. In this instance, it is unlikely

### Page **32** of **58**

that chemical - specific TTR data would be needed to further refine exposure assessments or would add appreciabl y to our general understanding of the availability of turf transferable pesticide residues. Guideline 875.2100 - Dislodgeable Foliar Residue (DFR) In accordance with 40 CFR 158, DFR data are required for all occupational (e.g., crop, nursery , greenhouse use sites) or residential (e.g., ornamental and vegetable gardens, pick your own farms, retail tree farms) uses that could result in post - application exposure to foliage. Since metconazole does not result in adverse s ys temic toxicity via the dermal route of exposure, EPA is waiving the 40 CFR DFR data requirement at this time. **6. 3**  **Residential Risk Estimates for Us e in Aggregate Assessment**  Table 6 .3.1 reflects the residential risk estimates that are recommended for use in the aggregate assessment for metconazole.

 The recommended residential exposure estimate for use in the adult aggregate assessment reflects inhal ation exposure from WDG applications to turf with a manually pressurized handwand.  The recommended residential exposure estimate for use in the children 1<2 years old aggregate assessment reflects hand - to - mouth exposures from WDG metconazole application to turf. **Table 6**  **.3.1. Recommendations for the Residential Exposures for the Metconazole Aggregate Assessment.** Lifestage Exposure

Scenario Dose (mg/kg/day) 1 MOE 2

Dermal Inhalation Oral Total Dermal Inhalation Oral Total Adult Manually

Pressurized Handwand Lawns/Turf (WDG) N/A 0.00024 N/A **0.00024** N/A 6,300 N/A **6,300** Child (Short Term) Hand - to - Mouth

from WDG Application to Lawns/Turf N/A N/A 0.0091 **0.0091** N/A N/A 1,000 **1,000** 1 Dose = the highest dose for each applicable lifestage of all residential scenarios assessed. Table D .1. in Appendix D presents that Residential Handler Exposure and Risk Estimates and Table D .2 in Appendix D presents the Residential Post - application Exposure and Risk Estimates. 2 MOE = the MOEs associated with the highest residential doses. 

### 6. **4 Residential Bystander**  **Post -**  **application Inhalation Exposure**  Volatilization of pesticides may be a source of post - application inhalation exposure to individuals nearb y pesticide applications. 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, and received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipol y/ SAP/meetings/2009/120109meeting.html). The agency has evaluated the SAP report and has develope d a Volatilization Screening Tool and a subsequent Volatilization Screening Analy sis (http://www.regulations.gov/#!docketDetail;D=EPA - HQ - OPP - 2014 - 0219).

### Page **33** of **58**

During Registration Review, the agency will utilize this analy sis to determine if data (i.e., flux s tudies, route - specific inhalation toxicological studies) or further analysis is required for metconazole. **6. 5**  **Spray Drift** Spray drift is a potential source of exposure to those nearby pesticide applications. This is particularl y the case with aerial app lication, but, to a lesser extent, spray drift can also be a potential source of exposure from the ground application methods (e.g., groundboom and airblast) emplo yed for metconazole. The Agency has been working with the Spray Drift Task Force (a task force composed of various registrants which was developed as a result of a Data Call - Inissued by

EPA), EPA Regional Offices and State L ead Agencies for pesticide regulation and other parties to develop the best spray drift management practices (see the Agenc y’ s Spray Drift website for more information). 3 

### The Agency is also taking means to qualitatively and qualitatively

address spray

drift as a potential source of exposure in risk assessments for pesticides through existing programs such as Ag Drift and chemical specific properties of pesticides. The potential for spray drift will be quantitatively evaluated for each pesticide during the Registration Review process which ensures that all uses for that pesticide will be considered concurrently . **7.0 Aggregate**  **Exposure/Risk Characterization** In accordance with 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. For metconazole , potential exposures from food, drinking water, and residential scenarios were aggregated. **7.1 Acute Aggregate Risk**  The aggregate acute risk estimates include exposure to residues of metconazole in food and drinking water, and does not include dermal, inhalation , or incidental oral exposure. As demonstrated under section 5.4.3, acute aggregate risks are not of concern. **7.2 Short** **- Term Aggregate Risk**  There is potential short - term exposure to metconazole via dietary (which is considered bac kground exposure) and residential (which is considered primary) exposure pathway s. For adults, these pathway s lead to exposure via oral (background) as well as dermal and inhalation (primary) routes. The most conservative scenario s w ere chosen for each. For a description of the residential exposure scenarios considered in the aggregate assessment, see Section 6. 3 .

3 Available: http://www.epa.gov/opp0 0001/factsheets/spraydrift.htm

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The short - term aggregate MOE is 63 0 for children 1 to <2 years old , which are not of concern to HED. For adults, oral dietary and inhalati on risk estimates were co mbined using the total aggregated risk index (ARI) methodology since the LOCs for oral dietary exposure (100) and inhalation exposure (1 , 000) are different. The LOC ARIis 1; therefore, ARI s of less than 1 are risk estimates of co ncern. The short - term aggregate ARI of 5. 3 is not of concern to HED. **Table 7.2.1**  **. Short** **- Term**  **Aggregate Risk Calculations Lifestage**  **Residential Exposure**

**Scenario Incidental Oral or Inhalation**  **Exposure Oral**  **Dietary Ex** **posure Total**  **Combined MOE**  **2 Total** 

**Combined ARI**  **3 NOAEL**  **mg/kg/day Exposure** 

**mg/kg/day MOE**  **1 NOAEL**  **mg/kg/day Ch**  **ronic Dietary**

**(Food + Water) mg/kg/day**  **MOE 1**  Child 1 to <2 yrs Post - application hand to - mo uth activities on treated turf 9.1 0.0091 1,000 9.1 0.005391 1,7 00 63 0 NA Adult Inhalation Exposure to

Handlers on Turf 9.1 0.00024 6,300 9.1 0.002653 3,4 00 NA 5. 3 1 The Level of Concern MOE is 100. 2 Total Combined MOE = 1/ [(1/MOE Dermal ) + (1/MOE Oral )] 3 Aggregate Risk Index (ARI) = 1÷ (1 ÷ RI or al dietary ) + (1 ÷ RI inhalation) Risk Index (RI) = MOE ÷ LOC; Inhalation LOC = 1,000 and Oral Di etary LOC = 100 

### Updated Aggregate Assessment of Free Triazole & its Conjugates The addition of the new proposed uses does not increase the aggregate exposure to free triazoles and its conjugates. Therefore, the recentl y updated aggregate human health risk assessment for free triazoles and its conjugates remains unchanged and the aggregate estimates are below HED’s level of concern ( D414952, T. Morton, 10/24/20 13). **7.3 Chronic Aggregate Ris**  **k** Chronic exposure from the residential pathway is not anticipated based on the current metconazole use pattern. The chronic aggregate risk (food and drinking water) is below HED’s LOC (i.e., <100% cPAD for the general U.S. population and all population subgroups ) . See Section 5. 4.4 for details. **8.0 Cumulative Exposure/Risk Characterization**  Metc onazole is a member of the triazole - containing class of pesticides. Although conazoles act similarly in plants (fungi) by

inhibiting ergosterol biosy nthesis, 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 b y the s ame, or essentially the same, sequence of major biochemical events (EPA, 2002). In conazoles, however, a variable pattern of toxicological responses is found ; s ome are hepatotoxic and hepatocarcinogenic in mice. Some induce thy roid 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 clearl y under stood whether these biochemical events are directly connected to their toxicological outcomes. Thus, there is currentl y 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

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substances found to have a common mechanism of toxicity, see EPA’s website at http://www.epa.gov/pesticides/cumulative . Met conazole 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 highl y 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 c omprised 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 EPA HQ - OPP - 2005 - 0497. **9.0 Occupational Exposure/Risk Characterization**  Metconazole has been proposed for use on dry s helled p ea and b eans (except s oy bean) c rop s ubgroup 6C and s unflower c rop s ubgroup 20B . The petitioner also requested a crop group expansion to rapeseed crop s ubgroup 20A ; and crop group conversions to s tone f ruit crop group 12 - 12 , and tree nut crop group 14 - 12. HED reevaluated the existing occupational uses for rapeseed crop subgroup 20A, stone fruit crop group 12 - 12, and tree nut crop group 14 - 12 to incorporate updated occupational exposure assessment assumptions and the revised LOC for inhalation exposure assessment. The application rates presented for rapeseed crop subgroup 20A, stone fruit crop group 12 - 12, and tree nut crop group 14 - 12 represent the maximum registered application rates, or the wors t - case exposure scenario s . **9.1 Short** **- /Intermediate**  **- Term Handler Risk**  HED uses the term handlers to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct job functions or tasks related to a pplications and exposures can vary depending on the specifics of each task. Job requirements (amount of chemical used in each application), the kinds of equipment used, the target being treated, and the level of protection used b y a handler can cause expo sure levels to differ in a manner specific to each application event. Based on the anticipated use patterns from the proposed label, ty pes of equipment and techniques that can potentially

be used, occupational handler exposure is expected from the propo sed uses. Because dermal toxicity

endpoints for the appropriate duration of exposure (short - and intermediate - term) were not identified up to the limit dose, only occupational handler inhalation exposures/risks have been assessed. For inhalation exposure s, an additional 10X uncertainty factor is added because of the lack of an available subchronic inhalation toxicity study . Therefore, the total uncertainty factor that has been applied to the inhalation assessments of

### Page **36** of **58**

metconazole is 1000X for handler expo sure. Occupational inhalation exposure and risk resulting in MOEs greater than or equal to 1000 will not be of concern to HED (LOC = 1000). For the proposed uses of metconazole, all short - and intermediate - term occupational handler MOEs are not of conc ern at baseline PPE except for mixing/loading WDG for aerial application to c anola ( c rop s ubgroup 20A), s unflower ( c rop s ubgroup 20B), dry b eans and p eas ( c rop s ubgroup 6C) (short - term MOE = 540; intermediate - term MOE =1,900; LOC = 1,000). With the addition of a PF5 respirator, mixing/loading WDG for aerial application to these crops is not of concern (MOE = 2,700). Summaries of the short - and intermediate - term risk estimate s for occupational handlers applying metconazole are provided in Appendix E , Table s E . 1 and E . 2 . **9.2 Short** **- and Intermediate**  **- Term**  **Post -** **Application Risk**  HED uses the term post - application to describe exposures that occur when individuals are present in an environment that has been previously treated with a pesticide (also referred to as re entry exposure). Such exposures may occur when workers enter previously treated areas to perform job functions, including activities related to crop production, such as scouting for pests or harvesting. Post - application exposure levels vary over time and depend on such things as the ty pe of activity , the nature of the crop or target that was treated, the ty pe of pesticide application, and the chemical’s degradation p roperties. In addition, the timing of pesticide applications, relative to harvest activities, can greatl y reduce the potential for post - application exposure. **9.2.1 Dermal Post**  **- Application**  **Risk** Because dermal toxicity

endpoints for the appropriate duration of exposure (short - and intermediate - term) were not identified up to the limit dose, post - application dermal exposures/risks were not assessed. Guideline 875.2100 - Dislodgeable Foliar Residue In accordance with 40 CFR 158, DFR data are required for all occupational (e.g., crop, nursery , greenhouse use sites) or residential (e.g., ornamental and vegetable gardens, pick your own farms, retail tree farms) uses that could result in post - application exposure to foliage. Since metconazole does not res ult in adverse s ys temic toxicity via the dermal route of exposure, EPA is waiving the 40 CFR DFR data requirement at this time. In this instance, it is unlikely that chemical - specific DFR data would be needed to further refine exposure assessments or woul d add appreciabl y to our overall understanding of the availability of dislodgeable foliar pesticide residues for metconazole. Restricted Entry

Interval Since a quantitative dermal assessment was not required, the REI is based on the acute toxicity of metc onazole. Metconazole is classified as Toxicity Category I II via the dermal route and Toxicity Category IV for skin irritation potential. It is not a skin sensitizer. Under 40 CFR 156.208 (c) (2) (iii), ai’s classified as Acute III or IV for acute dermal, eye irritation and primary skin irritation are assigned a 12 - hour REI. Therefore, the [156 subpart K] Worker Protection Statement REIof 12 hours is adequate to protect agricultural workers from post - application exposures to metconazole.

### Page **37** of **58**

**9.2.2 In**  **halation Post -** **Application Risk**  There are multiple potential sources of post - application inhalation exposure to individuals performing post - application 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, and received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly /SAP/meetings/2009/120109meeting.html ). The agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA - HQ OPP - 2014 - 0219 ). During Registration Review, the agency will utilize this anal ys is to determine if data (i.e., flux studies, route - specific inhalation toxicological studies) or further anal ys is is required for metconazole. In addition, the Agency

is continuing to evaluate the available post - application inhalation exposure data generated by the Agri cultural Reentry Task Force. Given these two efforts, the Agency will continue to identify

the need for and, subsequently , the way to incorporate occupational post - application inhalation exposure into the agency's risk assessments. Although a quantitativ e occupational post - application inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercial handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in higher exposure than post - application exposure. Therefore, it is expected that these handler inhalation exposure estimates would be protective of most occupational post - application inhalation exposure scenarios. It should be noted that there is the po tential for inhalation exposure during the mechanical sweeping and windrowing of the tree nuts. However, since there is a long PHIof 25 day s, the post - application inhalation exposure potential is negligible and was not quantitatively assessed. Furthermo re, inhalation exposure during dusty mechanical activities such as shaking and mechanical harvesting is another potential source of post - application inhalation exposure. However, the airblast applicator scenario is believed to represent a reasonable worst case surrogate estimate of post - application inhalation exposure during these dusty mechanical harvesting activities. The non - cancer inhalation risk estimate for commercial airblast application is not of concern (i.e., MOE >1,000)

### Page **38** of **58**

**10.0 References**  N. Dodd , 11/07/2014 , D 423622 . Metconazole Acute and Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessment for the Section 3 Registration Actions on Pea and Bean, Dried Shelled, except Soy bean, Subgroup 6C and the Sunflower Subgroup 20B; Expansion of the Canola Tolerance to the Rapeseed Subgroup 20A; and Conversion of the Established Stone Fruit and Tree Nut Crop Groups to the Stone Fruit Group 12 - 12 and the Tree Nut Group 14 - 12. N. Dodd , 11/04/2014 , D 423623 . Metconazole . Petition for the Establishment of Permanent Tolerances and Registration for Use on the Pea and Bean, Dried Shelled, except Soy bean, Subgroup 6C and the Sunflower Subgroup 20B; Expansion of the Canola Tolerance to the Rapeseed Subgroup 20A; and Conversion of the Est ablished Stone Fruit and Tree Nut Crop Groups to the Stone Fruit Group 12 - 12 and the Tree Nut Group 14 - 12. Summary of Anal ytical Chemistry and Residue Data. K. Rury , 12/ 11 /2014 , D423992. METCONAZOLE. Occupational and Residential Exposure Assessment for Proposed Uses on Dry Shelled Pea and Beans (Except Soy bean) Crop Subgroup 6C and Sunflower Crop Subgroup 20B; Crop Group Expansion to Rapeseed Subgroup 20A; and Crop Group Conversions to Fruit, Stone, Group 12 - 12; and Nut, Tree, Group 14 - 12. Also a Re Evaluation of all existing Residential Uses of Metconazole. F . Khan , 0 9 / 30 /20 1 4 , D4 1 8 674 . Drinking Water Exposure Assessment for the Section 3 New Use of Metconazole on Pea and Bean (Dried Shelled, Subgroup 6C), and Sunflower (Subgroup 20B) . T. Morton, 10/24/20 13 , D414951. Common Triazole Metabolites: Updated Dietary (Food + Water) Exposure and Risk Assessment to Address The New Section 3 Registrations For Use of Propiconazole on Rapeseed Crop Subgroup 20A; Use of Difenoconazole on Rapeseed Crop Subgro up 20A; and Use of Tebuconazole on Imported Oranges. T. Morton, 10/24/20 13, D414952. Common Triazole Metabolites: Updated Aggregate Human Health Risk Assessment to Address The New Section 3 Registrations For Use of Propiconazole on Rapeseed Crop Subgrou p 20A; Use of Difenoconazole on Rapeseed Crop Subgroup 20A; and Use of Tebuconazole on Imported Oranges.

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**A ppendix**  **A .**  **Toxicology Profile and Executive Summaries A.1**  **Toxicology Data Requirements** The requirements (40 CFR 158.500) for food uses of metconazole are in the table below. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used. **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 no yes yes

yes yes

-- **n o**  ***** 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 waived ** yes no 870.7485 General Metabolism ................................ ...................... 870.7600 Dermal Penetration ................................ ........................ 870.7800 Immunotoxicity ................................ ............................. yes no yes yes

yes yes Special Studies for Ocular Effects

Ac ute Oral (rat) ................................ ........................... Subchronic Oral (rat) ................................ .................. Six - mo nth Oral (dog) ................................ .................. no no no no

no no ***** TXR0057053 , J. Leshin , 10/09/2014 waiver **not** granted ****** TXR0056405, K. Rury, 08/09/2012 waiver granted

### Page **40** of **58**

**A.2 Toxicity Profile**  **s Table A.2.1. Acute Toxicity of**  **Metconazole Table A.2.1.**  **Acute Toxicity Profile**
**– Metconazole Technical**  **Guideline No. Study Type**  **MRID(s) Results**  **Toxicity Category** 870.1100 Ac ute oral [mouse] 44721512 LD 50 = >566 mg/kg III 870.1100 Ac ute oral [rat] 44721512 LD 50 = >566 mg/kg III 870.1100 Ac ute oral [rat] 44721513 LD 50 = >1459 mg/kg III 870.1100 Ac ute oral [rat] 44721514 LD 50 = >5000 mg/kg IV 870.1200 Ac ute dermal [rat] 44721512 Dermal LD 50 > 2000 III 870.1200 Ac ute dermal [rabbit] 44721512 Dermal LD 50 > 2000 III 870.1200 Ac ute inhalation [ rat] 44721512 LD 50 = >5 .6 mg/L IV 870.2400 Ac ute eye irritation [rat] 44721513 mo derate irritant III 870.2500 Ac ute dermal irritation [rabbit] 44721513 mild irritant IV 870.2600 Skin sensitization [guinea pig] 44721513 neg. - 

### Table A.2.2. Non **- acute Toxicity Profile for**  **Metconazole Table A.**  **2.2. Subchronic,**  **Chronic and Other Toxicity Profile for Metconazole Technical**  **1 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 his topathological 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 **41** of **58**

**Table A. 2.2.**  **Subchronic, Chronic and Other Toxicity Profile**  **for Metconazole Technical 1**  **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, 3 000 (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 femal es) 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 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

### Page **42** of **58**

**Table A. 2.2.**  **Subchronic, Chronic and Other Toxicity Profile**  **for Metconazole Technical 1**  **Guideline No.**  **Study Type MRID No. (year)/**  **Classification /Doses Results**  870.3700 Prenatal development

in rodents (rat) 44721522 (1991)

0, 12, 30, 75 mg/kg/day Gavage Acceptable/Guideline **Maternal** NOAEL = 75 mg/kg/day LOAEL > 75 mg/kg/day , not established. D ecreas ed body weight gain wa s observed at 30 mg/kg/day and higher, upon which the maternal LOAEL was based in previous risk assessments . However, body weight gain changes without changes in absolute body weight are not currently considered an adverse effect, so th ere is currently no maternal LOAEL. **Developm ental**  NOAEL = 12 mg/kg/day LOAEL = 30 mg/kg/day based on increased incidence of skeletal variations (predominantly lumbar ribs). At 75 mg/kg/day increased incidence of post - implantation loss, hydrocephaly and visceral anomaliea (cranial hemorrhage, dilated renal pelvis, dilated ureters, and displaced testis) were reported. 870.3700 Prenatal development

in rodents (rat) 46808443 (2 002)

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 . **Developm ental**  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) D efinitive Study 44721602 (1997)

0, 5, 10, 20, 40 mg/kg/day gavage Acceptable/Guideline **Materna** l NOAEL = 20 mg/kg/day LOAEL = 40 mg/kg/day based on reduction in food consumption, and changes in various hematology parameters (reductions in hematocrit, hemogl obin, mean corpuscular volume and increases in platelet counts and alkaline phosphatase activity). **Developm enta**  l NOAEL = 20 mg/kg/day LOAEL = 40 mg/kg/day based on increases in post - im plantation losses.

### Page **43** of **58**

**Table A. 2.2.**  **Subchronic, Chronic and Other Toxicity Profile**  **for Metconazole Technical 1**  **Guideline No.**  **Study Type MRID No. (year)/**  **Classification /Doses Results**  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 **Materna** l NOAEL = 25 mg/kg/day LOAEL = 62.5 mg/kg/day based on body weight changes and slight clinical signs (anorexia/reduced or altered fe cal output, cold ears). **Developm enta**  l 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 w ere observed at 10 mg/kg/day in Experiment #2, but not at that same dose in Experiment #1. 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/Guid eline **Parental/System ic**  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 animal s, and increased incidence of spleen cong estion 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), incre ase in spleen weights at 24 months (F), and increased hepatocellular lipid vacuolation (M/F) and centrilobular hypertrophy (M/F).

### Page **44** of **58**

**Table A. 2.2.**  **Subchronic, Chronic and Other Toxicity Profile**  **for Metconazole Technical 1**  **Guideline No.**  **Study Type MRID No. (year)/**  **Classification /Doses Results**  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 increased alkaline phosphatase activity (both sexes) and increased incidence of Kupffer cell pigmentation (females).
870.4200 a 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 va cuolation (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 mo nonuclear cell leukemia (F). 870.42 00b Carcinogenicity mo use 44721612 (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 cyto toxic 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 I

n vitro Cy

togenetics 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 S 9 activation.

### Page **45** of **58**

**Table A. 2.2.**  **Subchronic, Chronic and Other Toxicity Profile**  **for Metconazole Technical 1**  **Guideline No.**  **Study Type MRID No. (year)/**  **Classification /Doses Results**  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 I

n 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 870.7485 Metabolism and

pharmacokinetics: rat 44721622 (1992) single high dose: 164 mg/kg Radiolabel: (cyclopentyl 14 C ) 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 l ow

dose: 2 mg/kg Radiolabel: (cyclopentyl 14 C) 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 - 14 C) Acceptable/Guideline Approximately 96% of radioactivity in excreta after seven days: feces (76%) and urin e (20%). Metabolite information presented.
870.7485 Metabolism and

pharmacokinetics: rat WL136184* *cis only isomer 44721625 (1991)

single low dose: 2 mg/kg Radiolabel: (Cyclopentyl - 14 C) 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 Lo w 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 wa s slightly shorter in males than females, ~20 - 25 hours and ~34 hours, respectively.

### Page **46** of **58**

**Table A. 2.2.**  **Subchronic, Chronic and Other Toxicity Profile**  **for Metconazole Technical 1**  **Guideline No.**  **Study Type MRID No. (year)/**  **Classification /Doses Results**  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 Sy stemic NOAEL: 52 mg/kg/day. LOAEL: > 52 mg/kg/day I mmunotoxicity NOAEL: 52 mg/kg/day. LOAEL: > 52 mg/kg/day Non guideline 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, palmitoyl CoA oxidation, or peroxi some proliferation (in term s of peroxisome number or morphology). Non guideline 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 **47** of **58**

**Appendix B. Physicochemical Properties of**  **Metconazole .**  **Table B. Physicochemical Properties of Metconazole**  Parameter Value Reference s* (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 d ensity (20°C) 1.14 (relative density to water at 4 ° C , using capillary stoppered, 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 - S - 474m) 44721505 Solvent solubility ( g/L ) at 2 0oC 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 - 5 Pa or 9.23 x 10 - 8 mm Hg (metconazole) < 1.04x10 - 5 Pa or 7.80 x 10 - 8 mm Hg ( cis - isomer) < 1.96x10 - 6 Pa 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 **48** of **58**

**Appendix C**  **. Review of Human Research**  The PHED Task Force, 1995. The Pesticide Handlers Exposure Database, Version 1.1. Electronic Database. Task Force Members: Health Canada, U.S. EPA, and the National Agricultural Chemicals Associations, released February 1995. The Agricultural Handler Exposure Task Force (AHETF) , 2011. The Occupational Handler Unit Exposure Surrogate Reference Table. U.S. EPA. Released June 21, 2011. Data from the Outdoor Residential Exposure Task Force (ORETF). HED Residential Standard Operating Procedures (2012).

### Page **49** of **58**

**Appendix D. Residential Handler and Post** **- application Exposure and Risk Estimates**  **Table D**  **.1. Residential Handler Non -**  **cancer Exposure and Risk Estimates for Metconazole.**

Exposure Scenario Formulation Inhalation Unit Exposure (mg/lb ai) Maximum Application

Rate 1 Area

Treated or Amount Handled Daily 2 Inhalation Dose (mg/kg/day) 3 MOE 4 Mixer/Loader/Applicator Manually Pressurized Handwand

– Gardens/Trees & Lawns/Turf Liquid 0.018 0.00034 lb ai/gal 5 gal 0.00000038 3,900,000 Hose - End Sprayer

– Gardens/Trees Liquid 0.0014 0.00034 lb ai/gal 11 gal 0.000000065 23,000,000 Backpack Sprayer

– Gardens/Trees &

Lawns/Turf Liquid 0.14 0.00034 lb ai/gal 5 gal 0.0000030 500,000 Manually Pressurized Handwand

– Lawns/Turf WDG 1.1 0.0034 lb ai/gal 5 gal 0.00024 6,300 Manually Pressurized Handwand

–

Gardens/Trees WDG 1.1 0.000014 lb ai/ft2 1200 ft2 0.00023 6,600 Hose - End Sprayer

– Gardens/Trees WDG 0.0014 0.000014 lb ai/ft2 1200 ft2 0.00000029 5,200,000 Hose - End Sprayer- Lawns WDG 0.022 0.6 lb ai/A 0.5 acres 0.000083 18,000 Backpack Sprayer

– Lawns/Turf WDG 1.1 0.0034 lb ai/gal 5 gal 0.00024 6,300 Backpack Sprayer

– Gardens/Trees WDG 1.1 0.000014 lb ai/ft2 1200 ft2 0.00023 6,600 Push - Type Rotary Spreader

– Lawns/Turf Granular 0.0026 0.6 lb ai/A 0.5 acres 0.0000096 160,000 Belly Grinder

– Lawns/Turf Granular 0.039 0.000014 lb ai/ft2 1200 ft2 0.0000079 190,000 Spoon

– Lawns/Turf Granular 0.087 0.000014 lb ai/ft2 100 ft2 0.0000015 1,000,000 Cup

– Gardens/Trees Granular 0.013 0.000014 lb ai/ft2 1200 ft2 0.0000026 570,000 Cup

– Lawns/Turf Granular 0.013 0.000014 lb ai/ft2 100 ft2 0.00000022 6,800,000 Hand Dispersal

– Gardens/Trees Granular 0.38 0.000014 lb ai/ft2 1200 ft2 0.000077 19,000 Hand Dispersal

– Lawns/Turf Granular 0.38 0.000014 lb ai/ft2 100 ft2 0.0000064 230,000 Shaker Can

– Gardens/Trees Granular 0.013 0.000014 lb ai/ft2 1200 ft2 0.0000026 570,000 Shaker Can

– Lawns/Turf Granular 0.013 0.000014 lb ai/ft2 100 ft2 0.00000022 6,800,000 1 Based on registered label (EPA Reg. Nos. 59639 - 182 (Liquid), 59639 - 181 (Granular), and 59639 - 144 (WDG)). 2 Based on HED’s 2012 Residential SOPs (http://www.epa.gov/pesticides/science/residential - exposure - sop.html ). 3 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A/day or gallons/day) ÷ BW (80 kg). 4 Inhalation MOE = Inhalation NOAEL (9.1 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

### Page **50** of **58**

**Table D**  **.2. Residential Post**  **- application Non**  **- cancer Exposure and Risk Estim**  **ates for Metconazole. Lifestage**  **Post -**  **application Exposure**

**Scenario Formulation**  **Application Rate**  **1 Dose** 

**(m g/k** **g/day) 2**  **MOEs 3**  **Use Site Route of** 

**Exposure** Short - Term

Child Lawns/Turf Object to Mouth Granular 0.6 lb ai/A 0.000055 160,000 Hand to Mouth Granular 0.00091 10,000 Soil Ingestion Granular 0.000020 450,000 Object to Mouth WDG 0.6 lb ai/A 0.00028 33,000 Hand to Mouth WDG 0.0091 1,000 Soil Ingestion WDG 0.000020 450,000 1 Based on registered labels (Reg. Nos. 59639 - 181 (Granular) and 59639 - 144 (WDG)). 2 Dose (mg/kg/day) equations provided in 2012 Residential SOPs (http://www.epa gov/pesticides/science/residential - exposure sop.html) 3 MOE = POD (9.1 mg/kg/day) ÷ Dose (mg/kg/day).

### Page **51** of **58**

**Appendix E. Occupational Handler Exposure and Risk Estimates**  **Table E**  **.1. Short -**  **Term Occupational Handler Non**  **- Cancer Exposure and Risk Estimates for Metconazole.**  **Exposure Scenario Crop or Target**  **Level of Concern**  **Inhalation Unit**

**Exposure (μg/lb ai) 1**  **Ma xim**  **um Application**  **Rate 2**  **Area Treated or**

**Am ount Handled**  **Daily 3**  **Inhalation [Mitigation]**  **Dose (mg/kg/day) 4**  **MOE 5**  Mixer/Loader Mixing/Loading WDG for Aerial Application Stone Fruits (Crop Group 12 - 12)

1000 8.96 [baseline, no respirator] 0.125 lb ai/A 350 acres 0.0049 1,900 Tree Nuts (Crop Group 14 - 12) 0.11 lb ai/A 350 acres 0.0043 2,100 Canola (Crop Subgroup 20A), Sunflower (Crop Subgroup 20B), Dry Beans and Peas (Crop Subgroup 6C) 0.125 lb ai/A 1200 acres 0.017 540 1.792 [PF5 respirator] 0.0034 2,700 Mixing/Loading WDG for Airblast Application Stone Fruits (Crop Group 12 - 12)

8.96 [baseline, no respirator] 0.125 lb ai/A 40 acres 0.00056 16,000 Tree Nuts (Crop Group 14 - 12) 0.11 lb ai/A 0.00049 18,000 Mixing/Loading WDG for Chemigation Application Stone Fruits (Crop Group 12 - 12) 0.125 lb ai/A 350 acres 0.0049 1,900 Tree Nuts (Crop Group 14 - 12) 0.11 lb ai/A 0.0043 2,100 Canola (Crop Subgroup 20A), Sunflower (Crop Subgroup 20B), Dry Beans and Peas (Crop Subgroup 6C) 0.125 lb ai/A 0.0049 1,900

Groundbooom Canola (Crop Subgroup 20A),

Sunflower (Crop Subgroup 20B), Dry Beans and Peas (Crop Subgroup 6C) 0.125 lb ai/A 200 acres 0.0028 3,300 Applicator Aerial Application Stone Fruits (Crop Group 12 - 12)

1000 0.0049 [baseline, no respirator] 0.125 lb ai/A 350 acres 0.0000027 3,400,000 Tree Nuts (Crop Group 14 - 12) 0.11 lb ai/A 0.0000024 3,900,000 Canola (Crop Subgroup 20A), Sunflower (Crop Subgroup 20B), Dry Beans and Peas (Crop Subgroup 6C) 0.125 lb ai/A 1200 acres 0.0000092 990,000 Airblast Application Stone Fruits (Crop Group 12 - 12) 4.71 [baseline, no respirator] 0.125 lb ai/A 40 acres 0.00030 31,000 Tree Nuts (Crop Group 14 - 12) 0.11 lb ai/A 0.00026 35,000 Groundboom Application Canola (Crop Subgroup 20A), Sunflower (Crop Subgroup 20B), 0.34 [baseline, no 0.125 lb ai/A 200 acres 0.00011 86,000

### Page **52** of **58**

**Table E**  **.1. Short -**  **Term Occupational Handler Non**  **- Cancer Exposure and Risk Estimates for Metconazole.**  **Exposure Scenario Crop or Target**  **Level of Concern**  **Inhalation Unit**

**Exposure (μg/lb ai) 1**  **Ma xim**  **um Application**  **Rate 2**  **Area Treated or**

**Am ount Handled**  **Daily 3**  **Inhalation [Mitigation]**  **Dose (mg/kg/day) 4**  **MOE 5**  Dry Beans and Peas (Crop Subgroup 6C) respirator] Flagger Flagging for Aerial Application Stone Fruits (Crop Group 12 - 12) 1000 0.35 [baseline, no respirator] 0.125 lb ai/A 350 acres 0.00019 48,000 Tree Nuts (Crop Group 14 - 12) 0.11 lb ai/A 0.00017 54,000 Canola (Crop Subgroup 20A), Sunflower (Crop Subgroup 20B), Dry Beans and Peas (Crop Subgroup 6C) 0.125 lb ai/A 0.00019 48,000 Mixer/Loader/Applicator Mixing/Loading/Applying with a Mechanically Pressurized Handgun Stone Fruits (Crop Group 12 - 12) 1000 3.9 [baseline, no respirator] 0.00125 lb ai/gal 1000 gallons 0.000061 150,000 Tree Nuts (Crop Group 14 - 12) 0.0011 lb ai/gal 0.000054 170,000 1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table”; Level of mitigation: Baseline, PPE, Eng. Controls. Aerial applicators = Eng. Controls, all other estimates are baseline PPE. 2 Based on proposed label (Reg. No. 59639 - 147). 3 Exposure Science Advisory Council Policy #9.1. 6 Inhalation Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/ μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Ha ndled Daily (A or gal/day) ÷ BW (80 kg). 7 Inhalation MOE = I

nhalation NOAEL (9.1 mg/kg/day) ÷ I nhalation Dose (mg/kg/day).

### Page **53** of **58**

**Table E.**  **2. Intermediate -**  **Term Occupational Handler Non**  **- Cancer Exposure and Risk Estimates for Metconazole.**  **Exposure Scenario Crop or Target**  **Level of Concern**  **Inhalation Unit**

**Exposure (μg/lb ai) 1**  **Ma xim**  **um Application**  **Rate 2**  **Area Treated or**

**Am ount Handled**  **Daily 3**  **Inhalation [Mitigation]**  **Dose (mg/kg/day) 6**  **MOE 7**  Mixer/Loader Mixing/Loading WDG for Aerial Application Stone Fruits (Crop Group 12 - 12)

1000 8.96 [baseline, no respirator] 0.125 lb ai/A 350 acres 0.0049 1,300 Tree Nuts (Crop Group 14 - 12) 0.11 lb ai/A 350 acres 0.0043 1,500 Canola (Crop Subgroup 20A), Sunflower (Crop Subgroup 20B), Dry Beans and Peas (Crop Subgroup 6C) 0.125 lb ai/A 1200 acres 0.017 380 1.792 [PF5 respirator] 0.0034 1,900 Mixing/Loading WDG for Airblast Application Stone Fruits (Crop Group 12 - 12)

8.96 [baseline, no respirator] 0.125 lb ai/A 40 acres 0.00056 11,000 Tree Nuts (Crop Group 14 - 12) 0.11 lb ai/A 0.00049 13,000 Mixing/Loading WDG for Chemigation Application Stone Fruits (Crop Group 12 - 12) 0.125 lb ai/A 350 acres 0.0049 1,300 Tree Nuts (Crop Group 14 - 12) 0.11 lb ai/A 0.0043 1,500 Canola (Crop Subgroup 20A), Sunflower (Crop Subgroup 20B), Dry Beans and Peas (Crop Subgroup 6C) 0.125 lb ai/A 0.0049 1,300 Mixing/Loading WDG for Groundboom Application Canola (Crop Subgroup 20A), Sunflower (Crop Subgroup 20B), Dry Beans and Peas (Crop Subgroup 6C) 200 acres 0.0028 2,300 Applicator Aerial Application Stone Fruits (Crop Group 12 - 12)

1000 0.0049 [baseline, no respirator] 0.125 lb ai/A 350 acres 0.0000027 2,400,000 Tree Nuts (Crop Group 14 - 12) 0.11 lb ai/A 0.0000024 2,700,000 Canola (Crop Subgroup 20A), Sunflower (Crop Subgroup 20B), Dry Beans and Peas (Crop Subgroup 6C) 0.125 lb ai/A 1200 acres 0.0000092 700,000 Airblast Application Stone Fruits (Crop Group 12 - 12) 4.71 [baseline, no respirator] 0.125 lb ai/A 40 acres 0.00030 22,000 Tree Nuts (Crop Group 14 - 12) 0.11 lb ai/A 0.00026 25,000 Groundboom Application Canola (Crop Subgroup 20A), Sunflower (Crop Subgroup 20B), Dry Beans and Peas (Crop 0.34 [baseline, no respirator] 0.125 lb ai/A 200 acres 0.00011 60,000

### Page **54** of **58**

**Table E.**  **2. Intermediate -**  **Term Occupational Handler Non**  **- Cancer Exposure and Risk Estimates for Metconazole.**  **Exposure Scenario Crop or Target**  **Level of Concern**  **Inhalation Unit**

**Exposure (μg/lb ai) 1**  **Ma xim**  **um Application**  **Rate 2**  **Area Treated or**

**Am ount Handled**  **Daily 3**  **Inhalation [Mitigation]**  **Dose (mg/kg/day) 6**  **MOE 7**  Subgroup 6C) Flagger Flagging for Aerial Application Stone Fruits (Crop Group 12 - 12) 1000 0.35 [baseline, no respirator] 0.125 lb ai/A 350 acres 0.00019 34,000 Tree Nuts (Crop Group 14 - 12) 0.11 lb ai/A 0.00017 38,000 Canola (Crop Subgroup 20A), Sunflower (Crop Subgroup 20B), Dry Beans and Peas (Crop Subgroup 6C) 0.125 lb ai/A 0.00019 34,000 Mixer/Loader/Applicator Mixing/Loading/Applying with a Mechanically Pressurized Handgun Stone Fruits (Crop Group 12 - 12) 1000 3.9 [baseline, no respirator] 0.00125 lb ai/gal 1000 gallons 0.000061 100,000 Tree Nuts (Crop Group 14 - 12) 0.0011 lb ai/gal 0.000054 100,000 1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table”; Level of mitigation: Baseline, PPE, Eng. Controls. Aerial applicators = Eng. Controls, all other estimates are baseline PPE. 2 Based on proposed label (Reg. No. 59639 - 147). 3 Exposure Science Advisory Council Policy #9.1. 6 Inhalation Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/ μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (A or gal/day) ÷ BW (80 kg). 7 Inhalation MOE = I

nhalation NOAEL (6.4 mg/kg/day) ÷ I nhalation Dose (mg/kg/day).

### Page **55** of **58**

**Appendix F**  **. Summaries of Field Residue Data Table**  **F .1. Summary of Residues from Field Trials with Metconazole.**  Crop Matrix Analyte Total Application Rate (lb ai/A) PHI

(days) n 1 Residues (ppm)

Min. 2 Max. 2 LAFT 3 HAFT 3 Median 3 Mean 3 SD 3 **BEAN, DRY (Proposed Use = 0.25 lb ai/acre total application rate, 21 -**  **day PHI)** Bean, dry Metconazole (sum of

cis - and trans - isomers) 0.245 - 0.259 19 - 23 13 <0.04 <0.04 <0.04 <0.04 0.04 0.04 N/A TA 0.245 - 0.259 19 - 23 13 <0.02 0.348 <0.02 0.346 0.021 0.048 0.090

**PEA, DRY (Proposed Use = 0.25 lb ai/acre total application rate, 21 -**  **day PHI)** Pea, dry Metconazole (sum of

cis - and trans - isomers) 0.250 - 0.258 20 - 22 5 <0.04 <0.0620 <0.04 <0.0562 0.040 0.043 0.007 Pea, dry TA 0.250 - 0.258 20 - 22 5 0.155 3.16 0.187 2.38 0.591 0.864 0.869

**SUNFLOWER** ( **Proposed Use = 0.25 lb ai/acre total application rate, 21 -**  **day PHI)** Sunflower seed Metconazole (sum of

cis - and trans - isomers) 0.245 - 0.259 20 - 21 10 <0.04 0.968 <0.04 0.440 0.067 0.127 0.131 Sunflower seed TA 0.245 - 0.259 20 - 21 10 <0.02 0.252 <0.02 0.148 0.049 0.054 0.039 1 n = number of field trials. 2 Values based on total number of samples. 3 Values based on per - trial averages. LAFT = lowest average field trial, HAFT = highest average field trial, SD = standard deviation. For computation of the LAFT, HAFT, median, mean, and standard deviation, value s <LOQ are assumed to be at the LOQ (0.04 ppm for total metconazole and 0.02 ppm for TA). N/A = Not applicable. **Table F**  **.2. Summary of Residue Data from** **Crop Field Trials with Metconazole (WDG).** Crop matrix Total Applic.

Rate (lb ai/A) PHI

(days) Residue Levels (ppm) 1

n Min. Max. HAFT 2 Median Mean Std. Dev. **Canola (proposed use = 0.125 lb ai/A total application rate, 35 -**  **day PHI)** Canola seed 0.124 - 0.130 35 - 49 14 <0.04 <0.04 <0.04 0.04 0.04 NA

0.245 - 0.250 37 - 49 4 <0.04 <0.04 <0.04 0.04 0.04 NA 0.632 35 3 <0.04 <0.04 <0.04 0.04 0.04 NA 1 The LOQ is 0.02 ppm for each isomer, for a combined LOQ of 0.04 ppm. For calculation of the median, mean, and standard deviation, the LOQ was used for samples with residues <LOQ. 2 HAFT = Highest Average Field Trial. **Table F**  **.3. Summary of Residue Data for the Triazole Metabolites from** **Canola Field Trials with**

**Me tconazole (WDG).**  Commodity Total

Applic. Rate (lb ai/A) PHI

(days) Analyte Residue Levels (ppm) 1 n 2 Min. Max. HAFT 3 Median Mean Std. Dev. **Canola (proposed use = 0.125 lb ai/A total application rate, 35 -**  **day PHI)** Canola seed 0.124 - 0.130 35 - 49 1,2,4 - T 6 <0.01 <0.01 <0.01 0.01 0.01 NA TA 4 6 0.18 0.50 0.49 0.28 0.31 0.14 TAA 6 <0.01 <0.01 <0.01 0.01 0.01 NA 1 The LOQ is 0.01 ppm for each triazole analyte. For calculation of the median, mean, and standard deviation, the LOQ was used for samples with residues <LOQ. 2 For triazole analysis, seed samples were pooled by growing region to yield 3 pooled samples t hat were each analyzed in duplicate. Seeds from Trial F were not included in the pool samples as they were not of commercial quality. 3 HAFT = highest average residues from pooled regional samples. 4 TA residues were found in all control samples at 0.22 - 0 .27 ppm and averaged 0.24 ppm.

### Page **56** of **58**

**Table F**  **.4. Summary of Residue Data from** **Stone Fruit Crop Field Trials with Metconazole** Crop matrix Total Applic.

Rate (lb ai/A) PHI

(days) Analyte Residue Levels (ppm) 1 n Min. Max. HAFT 2 Median Mean Std. Dev. **STONE FRUIT (proposed use = 0.375 lb ai/A total application rate, 14**  **- day PHI)**  **1.81 lb/gal FlC form ulation**  Cherry 0.405 - 0.416

0.538 (1 trial) 13 - 14 cis - Metconazole 16 <0.02 0.134 0.119 0.041 0.048 0.032

trans - Metconazole 16 <0.02 0.028 0.025 0.020 0.021 0.002 **Me tconazole**  **16 <0.04**  **0.162 0.143**  **0.061 0.068**  **0.033** Peach 0.403 - 0.417

0.545 (1 trial) 13 - 14 cis - Metconazole 18 <0.020 0.073 0.066 0.027 0.030 0.015

trans - Metconazole 18 <0.020 <0.020 0.020 <0.020 <0.020 0.00 **Me tconazole**  **18 <0.040**  **<0.093 0.086**  **0.047 0.050**  **0.015** Plum 0.405 - 0.412

0.538 (1 trial) 13 - 14 cis - Metconazole 12 <0.020 0.04 0.06 0.020 0.024 0.008

trans - Metconazole 12 <0.020 <0.020 <0.020 <0.020 <0.020 -- **Me tconazole**  **12 <0.040**  **<0.060 0.060**  **0.040 0.044**  **0.008**

**50% WDG formulation**  Cherry 0.407 - 0.410 14 cis - Metconazole 4 0.027 0.056 0.052 0.039 0.040 0.014 trans - Metconazole 4 <0.02 <0.02 0.02 0.020 0.020 0.020 **Me tconazole**  **4 0.049**  **<0.076 0.076**  **0.068 0.065**  **0.011** Peach 0.418 14 cis - Metconazole 2 <0.02 0.020 0.02 0.02 0.02 -- trans - Metconazole 2 <0.02 <0.02 0.02 0.02 0.02 -- **Me tconazole**  **2 <0.04**  **<0.040 0.04**  **0.04 0.04**  **--** Plum 0.408 14 cis - Metconazole 2 <0.02 0.020 0.02 0.02 0.02 -- trans - Metconazole 2 <0.02 <0.02 0.02 0.02 0.02 -- **Me tconazole**  **2 <0.04**  **<0.040 0.04**  **0.04 0.04**  **--** 1 Values for “Metconazole” and “Total Residues” are reported on a sample basis and are therefore not summations of tabulated data. 2 HAFT = Highest average field trial result. **Table F**  **.5. Summary of Residue Data from** **Tree Nut Crop Field Trials with Metconazole**  **1** Crop matrix Total

Applic. Rate (lb ai/A) PHI

(days) Analyte Residue Levels (ppm) n Min. Max. HAFT 2 Median Mean Std. Dev. **TREE NUTS (proposed use = 0.44 or 0.50 lb ai/A total application rate, 25 -**  **day PHI) 1.81**  **lb/gal FlC form ulation**  Almond, hulls 0.543 - 0.570 25 cis - Metconazole 10 0.42 3.04 2.49 0.65 1.05 0.84 trans - Metconazole 10 0.08 0.65 0.50 0.13 0.22 0.19 **Me tconazole**  **10 0.50**  **3.69 2.82**  **0.78 1.27**  **1.03** 0.394 - 0.408 25 cis - Metconazole 4 0.30 0.62 0.62 0.48 0.47 0.17

trans - Metconazole 4 0.07 0.15 0.14 0.11 0.11 0.04 **Me tconazole**  **4 0.37**  **0.76 0.76**  **0.59 0.58**  **0.21**

### Page **57** of **58**

**Table F**  **.5. Summary of Residue Data from** **Tree Nut Crop Field Trials with Metconazole**  **1** Crop matrix Total

Applic. Rate (lb ai/A) PHI

(days) Analyte Residue Levels (ppm) n Min. Max. HAFT 2 Median Mean Std. Dev. Almond, nutmeat 0.543 - 0.570 25 cis - Metconazole 10 <0.02 <0.02 <0.02 0.02 0.02 -- trans - Metconazole 10 <0.02 <0.02 <0.02 0.02 0.02 -- **Me tconazole**  **10 <0.04**  **<0.04 <0.04**  **0.04 0.04**  **--** 0.394 - 0.408 25 cis - Metconazole 4 <0.02 <0.02 <0.02 0.02 0.02 --

trans - Metconazole 4 <0.02 <0.02 <0.02 0.02 0.02 -- **Me tconazole**  **4 <0.04**  **<0.04 <0.04**  **0.04 0.04**  **--** Pecan, nutmeat 0.502 - 0.537 25 - 32 cis - Metconazole 4 <0.02 <0.02 <0.02 0.02 0.02 -- trans - Metconazole 4 <0.02 <0.02 <0.02 0.02 0.02 -- **Me tconazole**  **6 <0.04**  **<0.04 <0.04**  **0.04 0.04**  **--**

**50% WDG formulation** Almond, hulls 0.402 - 0.407 25 cis - Metconazole 4 <0.02 1.69 1.51 0.68 0.77 0.87 trans - Metconazole 4 <0.02 0.33 0.31 0.15 0.16 0.17 **Me tconazole**  **4 <0.04**  **2.02 1.82**  **0.83 0.93**  **1.04** Almond, nutmeat 0.402 - 0.407 25 cis - Metconazole 4 <0.02 <0.02 <0.02 0.02 0.02 -- trans - Metconazole 4 <0.02 <0.02 <0.02 0.02 0.02 -- **Me tconazole**  **4 <0.04**  **<0.04 <0.04**  **0.04 0.04**  **--** Pecan, nutmeat 0.529 26 cis - Metconazole 2 <0.02 <0.02 <0.02 0.02 0.02 -- trans - Metconazole 2 <0.02 <0.02 <0.02 0.02 0.02 -- **Me tconazole**  **2 <0.04**  **<0.04 <0.04**  **0.04 0.04**  **--** 1 Values for “Metconazole” and “Total Residues” are reported on a sample basis and are therefore not summations of tabulated data. 2 HAFT = Highest average field trial result.

### Page **58** of **58**

**Appendix G**  **. International Residue Limits Status Sheet**



## Metconazole (125619; 08/27/2014) Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 

### Codex 40 CFR §180.617 Metconazole [5 - [(4 - chlorophenyl)methyl] - 2,2 - dimethyl 1 - (1 H - 1,2,4 - triazol - 1 - ylmethyl)cyclopentanol] 5 - [(4 - chlorophenyl)methyl] - 2,2 - dimethyl - 1 - (1 H1,2,4 - triazol - 1 - yl methyl) cyclopentanol None


### Commodity 1 

### Tolerance (ppm) /Maximum Residue Limit (mg/kg) US Canada Mexico 2 

### Codex

F r uit , sto n e , gro u

p 1 2 - 1 2 0.2 0.2 American plums, apricots, beach plums, black

cherries, Canada plums, capulins, cherry plums, chicksaw plums, damson plums, fresh prune plums, Japanese apricots, Japanese plums, klamath plums, nanking cherries, nectarines, peaches, plumcots, plums, sloes, sweet cherries, tart cherries

Nut , tree , gro u

p 14 - 1 2 0.04 0.04 African tree nuts, almond nuts, beechnuts, black walnuts, Brazil nuts, Brazilian pine nuts, bunya nuts, bur oak nuts, butternuts, Cajou nuts, candlenuts, cashew nuts, chestnuts, chinquapin nuts, coconuts, coquito nuts, dika nuts, Engl ish walnuts, ginkgo nuts, Guiana chestnuts, hazelnuts (filbert), heartnuts, hickory nuts, Japanese horse - chestnuts, macadamia nuts, mongongo nuts, monkey -pot nuts, mo nkey puzzle nuts, Okari nuts, Pachira nuts, peach palm nuts, peanuts, pecan nuts, pequi nuts, Pili nuts, pine nuts, pistachio nuts, Sapucaia nuts, tropical almond nuts, yellow horn nuts P e a and b ean , drie d s h elle d , e x cep t so y

b ean , s ub gro u

p 6 C 0.15 0.15 Dry (adzuki beans, beans, blackeyed peas, broad beans, catjang seeds, chickpeas, cow pea seeds, field peas, guar seeds, kidney beans, lablab beans, lentils, lima beans, moth beans, mung beans, navy beans, pigeon peas, pink beans, pinto beans, rice beans, southern peas, tepary beans, urd beans, grain lupin 0.05 dry soybeans Rap esee d sub gro u

p 20 A 0.08 0.08 Seeds (borage, cuphea, echium, flax, gold of

pleasure, hare's ear mustard, milkweed, mustard (oilseed type), oil radish, poppy, rapeseed (canola), sesame, sweet rocket Sun flo we r s ub gro u

p 20 B 0.7 Com pleted: M. Negussie; 08/27/2014 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.