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

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

### MEMORANDUM **Date :**  July

3 , 201 3 **SUBJECT: Py**  **raclostrobin**

– Human Health Risk Assessment for a Section 3 Registration of

N ew U ses on S ugarcane, G lobe Artichoke, Belgium Endive, P ersimmon, Greenhouse Grown T omato Transplants for H ome C onsumer M arket, and Residential O rnamentals, L andscape G ardens, F ruit Trees , and Nut Trees ; Plus Crop Group Expansions/Revisions for Bulb Vegetable Group 3
- 07, Fruiting Vegetable Group 8
- 10, Citrus Fruit Group 10
- 10, Pome Fruit Group 11
- 10, Berry Subgroups 13
- 07A, B, F, and G, and Oilseed Group 20
. **PC Code:** 0 99100 **DP Barcode:** D403462, D 39 8877 , D405065, D406472, D406652 **Decision No s**  **.:** 465126, 468304, 459294, 470110, 467106 **Registration No s**  **. :**  7969
- 185, 7969
- 186, 7969
- 247, 7969
- 258, 7969
- 289, 7969
- 291, 7969
- 199, 7969
- 251, 7969
- GLG, 4
- UII **Petition No .:**  2F8038, 2F8069 **Regulatory Action:** Section 3 Registration **Risk A**  **ss essment Typ**  **e :**  Single Chemical/Aggregate **Case No.:** NA **T XR No.:**  NA **CAS No.:** 175013
- 18
- 0 **MRID No.:** NA **40 CFR:** 180.58 2 

### FROM: Barry

O’Keefe , Senior Biologist Vincent Chen , Toxicologist Steve Funk , Senior Chemist Cassi Walls, Senior 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:** Heather Garvie , Risk Manager

Dominic S chul er , Risk Manager Robert Westin , Risk Manager Fungicide Branch Registration Division (7505P) and Andrew Ertman, Risk Manager Risk Integration, Minor Use and Emergency Response 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 p yr aclostrobin. The toxicology reevaluation was performed by Vincent Chen , the drinking water assessment was conducted by Faruque Khan (EPA Environmental Fate and Effects Division (EFED)), the review of the residue chemistry data and the dietary

exposure assessment w ere conducted by Steve Funk, the occupational and residential exposure assessment was conducted b y Cassi Walls , and human health risk assessment w as conducted b y Barry

O’Keefe
.

### Page 3 of 58

**1.0 Executive Summary** 
................................ ................................ ................................ ........... 5 **2.0 HED Recommendations** 
................................ ................................ ................................ .... 7 **2.1 Data Deficiencies** 
................................ ................................ ................................ ............ 8 **2.2.1 Enforcement Analytical Method** 
................................ ................................ ............... 8 **2.2.2 Recommended Tolerances** 
................................ ................................ ......................... 8 **2.2.3 Revisions to Petitioned**  **- For Tolerances** 
................................ ................................ .. 11 **2.2.4 International Harmonization** 
................................ ................................ ................... 12 **3.0 Introduction** 
................................ ................................ ................................ ...................... 13 **3.1 Chemical Identity** 
................................ ................................ ................................ ......... 14 **3.2 Physical/Chemical Characteristics** 
................................ ................................ ............. 14 **3.3 Pesticide Use Pattern** 
................................ ................................ ................................ .... 14 **3.4 Anticipated Exposure Pathways** 
................................ ................................ ................. 17 **3.5 Consideration of Environ**  **mental Justice**
................................ ................................ .... 18 **4.0 Hazard Characterization and Dose**  **- Response Assessment** 
................................ .......... 18 **4.1 Toxicology Studies Available for Analysis** 
................................ ................................ . 18 **4.2 Absorption, Distribution, Metabolism and Excretion (ADME)** 
.............................. 19 **4.2.1 Dermal Absorption** 
................................ ................................ ................................ ... 19 **4.3 Summary of Toxicological Effects** 
................................ ................................ .............. 19 **4.4 Safety Factor for Infants and Children (FQPA Safety Factor)** 
............................... 20 **4.4.1 Completeness of**  **the Toxicology Database**
................................ .............................. 20 **4.4.2 Evidence of Neurotoxicity** 
................................ ................................ ........................ 20 **4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal** 
........ 20 **4.4.4 Residual Uncertainty in the Exposure Database** 
................................ ................... 21 **4.5.1 Dose**  **- Response**  **Assessment**
................................ ................................ ...................... 21 **4.5.2 Recommendation for Combining Routes of Exposure for Risk Assessment** 
...... 22 **4.5.3 Cancer Classification and Risk Assessment Recommendation** 
............................ 23 **4.5.4 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** 
................................ ................................ ................................ .... 25 **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** 
................................ ................................ ......... 30 **5.4.5 Summary Table** 
................................ ................................ ................................ ......... 30 **6.0 Residential (Non**  **- Occupational) Exposure/Risk Characterization** 
............................. 30 **6.1 Residential Handler Exposure** 
................................ ................................ .................... 31 **6.2 Post**  **- Application Exposure** 
................................ ................................ .......................... 33 **6.3 Combined Residential Risk Estimates (Multiple Exposure Scenarios)** 
................... 35 **6.4 Residential Risk Estimates for Use in Aggregate Assessment** 
................................ .. 35 **6.5 Residential Bystander Post**  **- application Inhalation Exposure** 
................................ . 36 **6.6 Spray Drift** 
................................ ................................ ................................ .................... 36

### Page 4 of 58

**7.0 Aggregate Exposure/Risk Characterization** 
................................ ................................ .. 37 **7.1 Acute Aggregate Risk** 
................................ ................................ ................................ ... 37 **7.2 Short** **- Term Aggregate Risk** 
................................ ................................ ........................ 37 **7.3 Intermediate**  **- Term Aggregate Risk** 
................................ ................................ ........... 38 **7.4 Chronic Aggregate Risk** 
................................ ................................ .............................. 38 **8.0 Cumulative Exposure/Risk Characterization** 
................................ ............................... 38 **9.0 Occupational Exposure/Risk Characterization** 
................................ ............................ 39 **9.1 Short** **- /Intermediate**  **- Term Handler Risk** 
................................ ................................ ... 39 **9.2 Short** **- and Intermediate**  **- Term Post**  **- Application Risk** 
................................ .............. 40 **9.2.1 Dermal Post**  **- Application Risk** 
................................ ................................ ................. 40 **9.2.2 Inhalation Post** **- Application**  **Risk**
................................ ................................ ............ 41 **10.0 References** 
................................ ................................ ................................ ......................... 42 **Appendix A. Toxicology Profile and Executive Summaries**
................................ .................. 43 **A.1 Toxicology Data Requirements** 
................................ ................................ ................... 43 **A.2 Toxicity Profiles** 
................................ ................................ ................................ ............ 43 **Appendix B. Physicochemical Properties of Pyraclostrobin.**
................................ ................. 50 **Appendix C. Review of Human Research**
................................ ................................ ................ 50 **Appendix D. Summaries of Field Residue Data**
................................ ................................ ...... 51 **Appendix E. Summaries of Occupational Handler and Post -**  **application Exposure and Risk Estimates** 
................................ ................................ ................................ ................................ ...... 53 **Appendix F. Summary of Pyraclostrobin DFR Study Results** 
................................ .............. 57 **Appendix G. International Residue Limits Status Sheet**
................................ ....................... 58

### Page 5 of 58

**1.0 Executive Summary**  Introduction Py raclostrobin [carbamic acid, [2
- [[[1
- (4
- chlorophenyl)
- 1 H
-py razol
- 3
- yl ]oxy]methyl] phenyl]methoxy
- , methyl ester] belongs to the strobilurin class of fungicides (β
- methoxyacryl ate class of compounds). Strobilurins are s ynthetic analogs of a natural antifungal substance which inhibit spore germination, mycelial growth, and sporulation of the fungus on the leaf surface. Py raclostrobin is currently

registered on numerous agricultural crops and on residential and golf course turf. Use Profile The proposed actions of py raclostrobin are as follows: 1) BASF Corporation (BASF) is proposing a new agricultural use (PP# 2F8038) on sugarcane ; 2) The Interregional Research Project No. 4 (IR
- 4) is proposing new agricultural uses (PP# 2F8069) on artichoke, Belgium endive, and persimmon; 3 ) BASF is p roposing a new greenhouse tomato use for commercial production and for tomato transplants grown for the home consumer market ; 4 ) Bonide Products is proposing a new use on residential fruit and nut trees ; and 5 ) BASF is proposing new uses on residential orn amentals and landscape gardens
. Additionally, crop group expansions/revisions were requested for the bulb vegetable group 3
- 07, fruiting vegetable 8
- 10, citrus fruit group 10
- 10, pome fruit group 11
- 10, berry subgroups 13
- 07A, B, F, and G, and oilseed group 20. The proposed agricultural labels require occupational handlers to wear the following personal protective equipment (PPE): long
- sleeved shirts, long pants, chemical resistant gloves, and coveralls in a few cases. The 12 hour restricted entry interv al (REI) listed on the labels is appropriate. Exposure Profile The proposed residential u se s result in short
- term handler dermal and inhalation exposures for adults, short
- term post - application dermal exposures for adults, youths (11 to 16 years old), and children 6 to 11 years old, and short
- term post - application dermal and incidental oral exposures for children (1 to <2 ye ars old)
. Exposure pathways include dietary (food and drinking water), and residential exposure sources. Dietary exposures are al so expected for acute and chronic durations. Occupational exposures are expected via dermal and inhalation routes for short
- and intermediate
- term durations. Hazard Assessment Py raclostrobin has moderate to low acute toxicity via the oral, dermal, and inhalation routes of exposure. Py

raclostrobin is not a dermal sensitizer , but was determined to produce a low acute dermal effect and eye irritation . The primary target tissues appear to be mucosal membranes, with pathology

or secondary

effects (e.g. diarrhea) observed in different species. The primary effects were decreased body weight, body weight gain , and food consumption, and diarrhea. Py raclostrobin was classified as “Not likel y to be Carcinogenic to Humans.” There are no concerns for reproductive susceptibility , neurotoxicity , mutagenicity, genotoxicity, or immunotoxicity
. Based on the available data, toxicity endpoints and points of departure (PODs) have been selected for acute and chronic dietary , short
- term incidental oral, and short
- and inter mediate
- term dermal and inhalation exposure scenarios. Dermal absorption is 14%.

### Page 6 of 58

Inhalation toxicity is assumed to be equivalent to oral toxicity for non
- cancer risk assessments. The Food Quality

Protection Act (FQPA) Safety Factor has been reduced to 1 X because the toxicity database is complete, there is no concern for susceptibility in infants and young children, there are no neurotoxicity concerns, and there are no residual unc ertainties regarding exposure. Dietary Exposure The residue chemistry

data 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 ; i.e., for acute dietary 35.6 μg/L from surface water (from turf use) and for chronic dietary

2.3 μg/L from surface water (from turf use). The results of the acute dietary (food and drinking water) anal ys is using tolerance level res idues or highest field trial residues indicate that acute dietary risks do not exceed the Agency ’s level of concern ( LOC < 100% of the acute Population Adjusted Dose ( aPAD ) ) for the U.S. population and all subgroups. Combined dietary exposure from food and drinking water at the 95 th 

### percentile of exposure for the U.S. population is equivalent to 1.5% of the aPAD. The population subgroup with the highest estimated acute dietary exposure to py

raclostrobin is females 13
- 49 years, with an estimated exposure at the 95 th 

### percentile of 8 7 % of the aPAD. The results of the refined chronic dietary (food and drinking water) anal ys is using tolerance level residues or highest field trial residues and percent crop treated values are below the Agency ’s LOC for all population subgroups. The dietary exposure for food and drinking water for the general U.S. populatio n is 8. 0 % of the chronic Population Adjusted Dose (c PAD) and 2 7 % of the cPAD for children 1
- 2 years old , the population subgroup with the highest estimated chronic dietary exposure to py

raclostrobin. Residential Exposure New residential uses were requeste d in this action
. However , py ra clostrobin is currentl y registered for use on residential and golf course turf
. Existing residential exposure s and risks from use on turf w ere reassessed using the updated 2012 HED Residential Standard Operating Procedures 1 

### (SOPs). All residential handler dermal and inhalation exposure risk estimates were not of concern to HED, with m argins of e xposure (MOEs ) ranging from 5 9 0 to 3,9 00,000. All residential post
- application exposure risk estimates were also not of concern to HED, with M OEs rang ing from 150 to 34 0,000. Aggregate Exposure The adult aggregate MOE is 2 3 0, which includes post
- application exposure to treated turf and background dietary

exposure and is not of concern to HED. The aggregate MOE for children 1
- 2 ye ars old, including incidental oral exposures from treated turf, is 1 2 0, which is not of concern to HED. Occupational Exposure Based on the proposed use pattern of p yr aclostrobin , there is potential for short
- and intermediate
- term occupational exposure during mixing, loading, and other handling tasks; and
1 http://www.epa.gov/pesticides/science/residential
- exposure - sop.html

### Page 7 of 58

during post
- application activities. The proposed labels require occupational handlers to wear the following personal protective equipment (PPE): long
- sleeved shirts, long pants, and chemical resistant gloves. All of the dermal MOEs are not of concern with labeled PPE (gloves)
. The handler inhalation MOEs range from 33 to 8 , 500 at baseline PPE (no respirator). The two inhalation scenarios with MOEs below 100 at baseline PPE [mixing/loading of WDG formulation to support aerial and chemigation applications to artichoke and persimmon (MOE=33); and mixing/loading/appl ying (M/L/A) of WDG formulation using a mechanically pressurized handgun to treat greenhouse tomatoes (MOE=85)] were no longer a concern to H ED when assessed with a PF5 respirator (MOE s >100). A PF5 respirator need s to be proposed on the affected Pristine Fungicide [EPA Reg. No.7969
- 199] and Pagent® Fungicide [EPA Reg. No.7969
- 251] labels. The short
- and intermediate
- term post - application dermal exposure risk estimates for workers for all scenarios were not of concern on day 0 (12 hours after application) , with MOEs rang ing from 120 to 12,000. Based on the Agency's current practices, a quantitative occupational post
- application inhalation exposure assessment was not performed for p yraclostrobin 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 inh alation exposure assessment for py raclostrobin
. The 12 hour restricted entry interval (REI) listed on the labels is appropriate. Review of Human Research This risk assessment relies in part on data from studies in which adult human subjects were intentionally

exposed to a pesticide or other chemical. These 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 Residential SOPs (lawns and turf) , and MRID 45773201 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 b y the Human Studies Review Board. Descripti ons 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 considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low - Income Populations," (http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf
. **2.0 HED**  **Recommendations** HED has examined the toxicology and residue chemistry database s for py raclostrobin. Pending submission of revised Sections B and F, there are no toxicology or residue chemistry

issues that would preclude granting Section 3 registration for the requested uses of p yr aclostrobin, or establishment of tolerances for residues of p yr aclostrobin. Additional data are needed, as

### Page 8 of 58

outlined below in Section 2 .1. The specific tolerance recommendations are discussed in Section 2.2, and label modifications are discussed in Section 2.3. **2.1 Data Deficiencies**  None **2.2 Tolerance Considerations**  **2.2.1 Enforcement Analytical Method**  There are adequate residue anal ytical methods for tolerance enforcement. Two adequate methods are available for enforc ement purposes for residues of p yr aclostrobin and the metabolite BF 500
- 3 in/on plant commodities: an L C/MS/MS method (BASF Method D9 9 08) and an HPL C/UV method (Method D9904). The validated method LOQ for both py raclostrobin and BF 500
- 3 is 0.02 ppm in all tested plant matrices, for a combined LOQ of 0.04 ppm. Adequate independent method validation and radiovalidation data were submitt ed for both methods. Py raclostrobin was successfully evaluated through several of the FDA protocols, while recovery of BF 500
- 3 was unsuccessful in all protocols. The results of the multiresidue testing for py raclostrobin were forwarded to FDA on 1/4/02 for the purpose of updating the Pesticide Analytical Manual, Volume I ( PAM I)
. **2.2. 2**  **Recommended Tolerances** HED has examined the residue chemistry database for py

raclostrobin and evaluated the adequacy of submissions associated with the current action s . For the proposed use on sugarcane , a tolerance is required. A time
- limited Section 18 tolerance of 0.02 ppm exists (40 CFR §180.582(b). Based on evaluation of the sugarcane field trial data with the Organization for Economic Cooperation and Development (OECD) tolerance calculation procedure, a permanent tolerance of 0.2 ppm is appropriate for sugarcane, cane. P yraclostrobin residues did not concentrate in sugarcane molasses and sugarcane refined sugar. Therefore , these commodities are covered b y the to lerance for the raw agricultural commodity , sugarcane, cane. The proposed updating of certain existing crop groups and the removal of certain oilseed tolerances and certain previous crop group/subgroup tolerances are acceptable. However, an additional oi lseed tolerance will need to be removed, and IR
- 4 should request the following removal: cotton , undelinted seed (0.3 ppm). The Section 18 tolerance for Belgium endive should be removed concurrent with the establishment of the Section 3 tolerance for Bel gi um endive
. The recommended tolerances for py raclostrobin commodities or commodity groups are presented in Table 2.2.2.1. Compliance with the tolerance levels is to be determined b y measuring only

the sum of py

raclostrobin (carbamic acid, [2
- [[[1
- (4
- chlorophenyl)
- 1 H
- py razol
3
- yl ]oxy]methyl]phenyl]methoxy
- , methyl ester) and its desmethoxy metabolite (methyl N

- [[[1
-

### Page 9 of 58

(4
- chlorophenyl )
- 1 H

-py razol
- 3
- yl ]oxy]methyl]phenyl carbamate), calculated as the stoichiometric equivalent of py raclostrobin. **Table 2.2.2.1.**  **Tolerance Summary for Pyraclostrobin.**  **Comm odity**  **Proposed/Existing Tolerance (ppm)**  **Recommended/ Harm** **onized Tolerance (ppm)**  **Comments; Correct Commodity** 

**Definition** 40CFR§180.582(a) Artichoke, globe 3.0 3.0 Endive, b elgium 3.0 4.0 OECD statistical calculation estimates 4.0 ppm. Persimmon 3.0 3.0 Sugarcane, cane 0.2 0.2 0 Vegetable, bulb, group 3
- 07 0.9 0.9 Crop group update Vegetable, bulb, group 3 0.9 Remove Crop group update Vegetable, fruiting, group 8
- 10 1.4 1.4 Crop group update Vegetable, fruiting, group 8 1.4 Remove Crop group update Fruit, citrus, group 10
- 10 2.0 2.0 Crop group update Fruit, citrus, group 10 2.0 Remove Crop group update Fruit, pome, group 11
- 10 1.5 1.5 Crop group update Fruit, pome, group 11 1.5 Remove Crop group update Oilseed group 20 0.45 0.45 Crop group creation. Cotton, undelinted seed 0.3 Remove To be replaced by oilseed group 20. IR
- 4 needs to request this removal. Borage, seed 0.45 Remove To be replaced by oilseed group 20. Castor oil plant, seed 0.45 Remove To be replaced by oilseed group 20. Chinese tallowtree, seed 0.45 Remove To be replaced by oilseed group 20. Crambe, seed 0.45 Remove To be replaced by oilseed group 20. Cuphea, seed 0.45 Remove To be replaced by oilseed group 20. Echium, seed 0.45 Remove To be replaced by oilseed group 20. Euphorbia, seed 0.45 Remove To be replaced by oilseed group 20. Evening primrose, seed 0.45 Remove To be replaced by oilseed group 20. Flax, seed 0.45 Remove To be replaced by oilseed group 20. Gold of pleasure, seed 0.45 Remove To be replaced by oilseed group 20. Hare's ear mustard, seed 0.45 Remove To be replaced by oilseed group 20.

### Page 10 of 58

**Table 2.2.2.1.**  **Tolerance Summary for Pyraclostrobin.**  **Comm odity**  **Proposed/Existing Tolerance (ppm)**  **Recommended/ Harm** **onized Tolerance (ppm)**  **Comments; Correct Commodity** 

**Definition** Jojoba, seed 0.45 Remove To be replaced by oilseed group 20. Lesquerella, seed 0.45 Remove To be replaced by oilseed group 20. Lunaria, seed 0.45 Remove To be replaced by oilseed group 20. Meadowfoam, seed 0.45 Remove To be replaced by oilseed group 20. Milkweed, seed 0.45 Remove To be replaced by oilseed group 20. Mustard, seed 0.45 Remove To be replaced by oilseed group 20. Niger seed, seed 0.45 Remove To be replaced by oilseed group 20. Oil radish, seed 0.45 Remove To be replaced by oilseed group 20. Poppy, seed 0.45 Remove To be replaced by oilseed group 20. Rapeseed, seed 0.45 Remove To be replaced by oilseed group 20. Rose hip, seed 0.45 Remove To be replaced by oilseed group 20. Safflower, seed 0.45 Remove To be replaced by oilseed group 20. Stokes aster, seed 0.45 Remove To be replaced by oilseed group 20. Sunflower, seed 0.45 Remove To be replaced by oilseed group 20. Sweet rocket, seed 0.45 Remove To be replaced by oilseed group 20. Tallowwood, seed 0.45 Remove To be replaced by oilseed group 20. Tea oil plant, seed 0.45 Remove To be replaced by oilseed group 20. Vernonia, seed 0.45 Remove To be replaced by oilseed group 20. Caneberry subgroup 13
- 07A 4.0 4.0 Group update Bushberry subgroup 13
- 07B 4.0 4.0 Group update Small fruit, vine climbing subgroup (except fuzzy kiwi) 13
- 07F 2.0 2.0 Fruit, small vine climbing, except fuzzy kiwifruit, subgroup 13
- 07F Group update Lo w growing berry subgroup 13
- 07G except cranberry 1.2 1.2 Berry, low growing, subgroup 13
- 07G, except cranberry Group update

### Page 11 of 58

**Table 2.2.2.1.**  **Tolerance Summary for Pyraclostrobin.**  **Comm odity**  **Proposed/Existing Tolerance (ppm)**  **Recommended/ Harm** **onized Tolerance (ppm)**  **Comments; Correct Commodity** 

**Definition** Berry, group 13 4.0 Remove Group update . Replaced with subgroups 13
- 07A and 13
- 07B Grape 2.0 Remove Group update. Replaced with subgroup 13
- 07F Straw berry 1.2 Remove Group update. Replaced with subgroup 13
- 07G 40CFR§180.582(b ) Section 18 emergency exemptions Endive, b elgium 11.0 Remove Replaced with Section 3 tolerance for endive, b elgium Sugarcane, cane 0.02 Revoke Replaced with new tolerance in (a) Sugarcane, molasses 0.4 0 Revoke Replaced with new tolerance in (a) for sugarcane, cane 

### No new tolerances are proposed for p yr aclostrobin based on the proposed greenhouse use on fruiting vegetables. The existing tolerance for fruiting vegetables will cover the requested new uses of the PageantTM 

### fungicide (EPA Reg. No. 7969
- 251) formulation. No new tolerances are proposed for p yr aclostrobin based on the proposed residential use on pome fruit, stone fruit, and tree nuts using the proposed label for the Bonide Products, Inc FT09 ( EPA File Sy

mbol 4
- UII) . The existing tolerances based on the BASF Pristine ® 

### label cover the se residential uses on pome fruit, stone fruit, and tree nuts . The Bonide Products, Inc FT09 label compares favorably

with the BASF Pristine ® 

### label. Therefore, the existing tolerances for pome fruit, stone fruit, and tree nuts will also cover the proposed new residential uses. **2.2. 3**  **Revisions to Petitioned -**  **For Tolerances** The available data for Belgium endive will not support a tolerance level of 3.0 ppm. A revised Section F should be submitted with a tolerance for endive, Belgium at 4.0 ppm. Several crop group conversions were requested. Most were crop group updates. One request was to replace individual oilseed tolerances with an oilseed crop group 20 tolerance. This was accompanied b y a request to remove numerous individual commodity oilseed tolerances. These changes have been made to the proposed labels. In addition to the requested removals, the existing tolerance for cotton undelinted seed will be replaced b y oilseed group 20, and IR
- 4 needs to make this request. The tolerance covering undelinted cotton seed is raised from 0.3 ppm to 0.45 ppm. This is acceptable as cottonseed is one of the three representative commodities for the oilseed group (cottonseed, rapeseed, sunflower), and the highest estimate from the three commodities is adopted for the group. The changes are acceptable, as detailed in Table 2.2.2.1.

### Page 12 of 58

860.1550 Proposed Tolerances
 The available data for Belgium endive will not support a tolerance level of 3.0 ppm. A revised Section F should be submitted with a tolerance for endive, Belgium at 4.0 ppm.
 The existing tolerance for undelinted cottonseed seed should be removed as it is replaced by the proposed and recommended tolerance for oilseed group 20. A revised Section F should be submitted. **2.2. 4**  **International Harmonization** Codex and Canada have not established maximum residue limits (MRL s) for py raclostrobin on sugarcane , Belgium endive and persimmon . Therefore, there is no issue of harmonization at this time (see Appendix G). A Codex MRLhas been established for py raclostrobin in/on globe artichoke at 2.0 ppm. The recommended US tolerance is 3.0 ppm. Residue definitions are different in the US and in Codex, and the US tolerance is based on application of the OECD tolerance calculation procedure to the validated field trial data. The tolerance cannot be lowered to the Codex level as this could result in apparent violations for crops treated in accordance with the label. Canada does not have p yr aclostrobin tolerances for globe artichoke, Belgium endive, or persimmon. Therefore, there is no issue of harmonization with Canada at this time (see Appendix G). The crop group/subgroup conversions were considered for possible harmonization with Codex. The Codex has established an MRLfor one or more commodities in the bulb vegetable group 3
- 07, in the fruiting vegetables group 8
- 10, in the pome fruit group 11
- 10, in the caneb erry subgroup 13
- 07A, in the bushberry subgroup 13
- 07B, in the small fruit vine climbing subgroup 13
- 07F, and in the low growing berry subgroup 13
- 07G. The Codex has established an MRLfor the Codex equivalent of the US citrus fruit group 10
- 10 and for th e oilseed group 20. Harmonization with these groups or subgroups is not possible because the residue definitions used by the US and Codex are different. Therefore, the resulting numerical values refer to different residues. The US and Canadian residue definitions are harmonized. For the crop group conversions, the US is harmonized with Canada for bulb vegetables group 3
- 07, citrus fruit group 10
- 10, pome fruit group 11
- 10, oilseed group 20, caneberry subgroup 13
- 07A, bushberry subgroup 13
- 07B, small fruit, vine climbing subgroup 13
- 07F, and low growing berry subgroup 13
- 07G. The US is not harmonized with Canada for fruiting vegetables group 8
- 10, where the US group tolerances is 1.4 ppm and Canada has 1.0 ppm for tomato and pepper. The US is not harmonized with Canada for caneberry

subgroup 13.07A and for bushberry subgroup 13
- 07B. The US tolerances for caneberry

subgroup 13.07A and for bushberry subgroup 13
- 07B are 4.0 and 4.0 ppm, respectivel y, whereas the Can adian tolerances are 3.5 and 3.5 ppm, respectively
.

### Page 13 of 58

**2.3 Label Recommendations**  860.1200 Directions for Use
 A revised label is required for EPA Reg. No. 7969
- 247 (12.0% EC, Multiva®). The proposed label has a maximum seasonal rate of 0.52 lb ai/acre for sugarcane . However, the directions state that no more than 80 ounces of MultivaTM should be applied per season, which is equivalent to 0.68 lb ai. The 80 ounces is incorrect and must be changed to 62 ounces of product.
 The proposed labels for EPA Reg. No. 7969
- 199 (Pristine® Fungicide), and EPA Reg. No. 7969
- 187(Cabrio® EG Fungicide) provide directions for use on the low growing berry subgroup. Cranberry

must be removed from the list of crops. The title “low growing berry

subgroup” should be changed to “low growing berry subgroup except cranberry .”
 Revised labels are required for EPA Reg. No.7969
- 199 (Pristine Fungicide ) and EPA Reg. No.7969
- 251 (Pagent® Fungicide ). A PF5 respirator needs to be proposed on these labels. **3.0 In**  **troduction** Py raclostrobin belongs to the strobilurin class of fungicides (β
- methoxyacrylate class of compounds). Strobilurins are s ynthetic analogs of a natural antifungal substance which inhibit spore germination, mycel ial growth, and spo rulation of the fungus on the leaf surface. Py raclostrobin is currently

registered on barley , berries, Brassica vegetables, bulb vegetables, citrus, corn (field, pop and sweet), cotton, cucurbit vegetables, fruiting vegetables, grapes, grass grown for see d, hops, leafy vegetables, legumes (dried peas and beans, succulent shelled peas and beans), mint, oats, oilseed group (canola & flax), peanuts, pistachios, pome fruit s , potatoes, root vegetables, rye, soybean, strawberries, stone fruits, sugar beets, sunf lower, tropical fruits (avocado , black s apote , canistel , mamey s apote, m ango ; p apaya , s apodilla , & s tar a pple ), tuberous and corm vegetables, tree nuts, and wheat, as well as s eed treatment on o ats, c anola, and f lax , and residential and golf course turf. The proposed actions of py raclostrobin are as follows: 1) BASF Corporation (BASF) is proposing a new agricultural use (PP# 2F8038) on sugarcane; 2) The Interregional Research Project No. 4 (IR
- 4) is proposing new agricultural uses (PP# 2F8069) on artichoke, Belgium endive, and persimmon; 3) BASF is proposing a new greenhouse tomato use for commerci al production and for tomato transplants grown for the home consumer market ; 4) Bonide Products is proposing a new use on residential fruit and nut trees ; and 5) BASF is proposing new uses on residential ornamentals and landscape gardens . Additionally, crop group expansions/revisions were requested for the bulb vegetable group 3
- 07, fruiting vegetable 8
- 10, citrus fruit group 10
- 10, pome fruit group 11
- 10, berry subgroups 13
- 07A, B, F, and G, and oilseed group 20.

### Page 14 of 58

**3.1 Chemical Identity**  **TABLE 3.**  **1. Pyrac**  **lostrobin Nom**  **enclature.** Chemical Structure

Common name Py raclostrobin Company experimental name BAS 500 F IUPAC name methyl 2
- [1
- (4
- chlorophenyl)pyrazol
- 3
- yloxymethyl]
-N
- methoxycarbanilate CAS name methyl N
- [ 2
- [[[1
- (4
- chlorophenyl)
- 1 H
- pyrazol
- 3
- yl]oxy]methyl]phenyl]
-N
methoxycarbamate CAS registry number 175013
- 18
- 0 End
-use product (EP) Headline® EC Fungicide , EP A Reg. No. 7969
- 186. Cabrio® EG fungicide, EPA Reg. No. 7969
- 187
. Pristine® fungicide, EPA Reg. No. 7969
- 199
. Headline® SC fungicide, EPA Reg. No
. 7969
- 289
. 

### 3.2 **Physical/Chemical Characteristics** Py ra clostrobin has a log octanol/water partition coefficient ( log Kow

### ) of 3.9 9
. P yra clostrobin has a molecular weight of 387.82 g/mol; therefore, the potential to cross biological barriers is somewhat limited
. If released to air, a low vapor pressure of 1.9 ×1 0 - 8 

### mm Hg at 20 oC limiting the potential for volatilization. The physiochemical properties of py raclostrobin are summariz ed in Appendix B. **3.3 Pesticide Use Pattern**  Sugarcane BASF is proposing the use of Headline® Fungicide , Headline® SC Fungicide , MultivaTM Fungicide , and BAS 556 SC Fungicide on sugarcane at a maximum single application rate ranging from 0.13 to 0.20 lb ai/A using ground, aerial, or chemigation equipment. Each product may be applied 4 times per year at a maximum yearly application rate of 0.52 to 0.78 lb ai/A/y r and a 14
- day

retreatment interval. Headline® Fungicide (EPA Reg
. No. 7969
- 186) and Headline® SC Fungicide (EPA Reg
. No.7969
- 289) are suspension concentrate (SC) fungicides containing 23.6% py raclostrobin. MultivaTM Fungicide (EPA Reg
. No.7969
- 247) and BAS 556 SC Fungicide (EPA Reg
. No.7696
- 291) are multiple active ingredient (MAI) SC fungicides containing 12% p yrac l o strobin and 7.4 % metconazole, and 13.64% py rac l o strobin and 5.14% metconazole, respectively
. Globe artichoke, Belgium endive, and persimmon IR
- 4 is proposing the use of Pristine Fungicide on globe artichoke s, Belgium endive, and persimmons. Pristine Fungicide (EPA Reg
. No.7969
- 199) is a multiple active ingredient (MAI) N N Cl O N O C H 3 O OCH 3

### Page 15 of 58

water dispersible granular (WDG) fungicide containing 12.8% p yr aclostrobin and 25.2% boscalid. Belgium endive may be treated at a maximum rate of 0.013 lb ai/1000 lb roots prior to cold storage and 0.014 lb ai/70 ft2 

### prior to forcing, each at one application per season. The maximum single application rate for artichoke and persimmon is 0.18 lb ai/A using aerial, ground, or chemigation equipment. Pristine may be applied to artichoke and persimmon 3 times per crop cycle at a maximum crop
- cycle application rate of 0.55 lb ai/A/yr. Greenhouse tomato use for commercial production and for tomato transplants grown for the home consumer market BASF is proposing the use of Pagent® Fungicide on greenhouse grown tomatoes. Pagent® Fungicide label (EPA Reg
. No.7969
- 251) is a MAI WDG f un gi cide containing 12.8% py raclostrobin and 25.2% boscalid. Pagent may be applied at a maximum single application rate of 0.18 lb ai/A (or 0.0018 lb ai/gal). Pagent may be applied 3 times per crop cycle at a maximum crop - cycle application rate of 0.55 lb ai/A (or 0.0055 lb ai/gal). Handlers may appl y Pagent using handheld equipment. R esidential fruit and nut trees Bonide Products is proposing a new product, Bonide® Fruit Tree Spray Concentrate (FT09), for use on home orchard fruit and nut trees. Bonide® Fruit Tree Spray Concentrate (EPA Reg
. No. 4
- UII) is a MAI SC fungicide containing 0.500% lambda
- cy halothrin, 3.06% py

raclostrobin, and 5.622% boscalid
. The maximum single application rate is 0.12 lb ai/A with no more than 4 or 5 applications per ye ar, depending on the tree type. The retreatment interval ranges from 7 to 10 days. Residential handlers may appl y FT09 using handheld spray equipment. R esidential ornamentals and landscape gardens BASF is proposing a new product, Homeowner Garden Spray Fungici de, for use on residential ornamentals and landscape gardens via a residential applicator. Homeowner Garden Spray Fungicide (EPA Reg
. No. 7969
- GLG) is a MAI SC fungicide containing 9.0% py raclostrobin and 18.0% boscalid
. The maximum single application rate for this product is 0.0016 lb ai/gal via residential handheld spray equipment or hose
- end sprayers. The proposed agricultural labels require occupational handlers to wear the following personal protective equipment (PPE): long
- sleeved shirts, long pants, chemical resistant gloves, and coveralls in a few cases. The 12 hour restricted entry interval (REI) listed on the labels is appropriate. The proposed uses of p yr aclostrobin are summarized in Table 3.3
.

### Page 16 of 58

**Table 3.3. Use Profile for Proposed Pyraclostrobin Uses**  **Proposed Use**  **Product Formulation**

**[EPA Reg. No.] Application**  **Equipment Max. Single** 

**Applic. Rate (lb ai/A** **) Max.** 

**No. Applic.**  **Per Season**  **Max.**

**Seasonal Applic.**  **Rate (lb ai/A/yr** **) PHI** 

**(days) Use Directions and** 

**Lim itations** 

Sugarcane Headline® Fungicide

[EPA Reg
. No. 7969
- 186] SC 23.6% pyraclostrobin Headline® SC Fungicide [EPA Reg No.7969
- 289] SC 23.3% pyraclostrobin
G round, Aerial, or Chemigation 0.20 4 0.78 14 Do not make more than two sequential applications. Continue treatment on a 14 to 28 day interval. MultivaTM Fungicide [EPA Reg
. No.7969
- 247] SC 12% pyraclostrobin 0.13 4 0.52 14 Do not make more than two sequential applications. Continue treatment on a 14 to 28 day interval. BAS 556 SC Fungicide [EPA Reg
. No.7696
- 291] SC 13.64% pyraclostrobin 0.19 4 0.76 14 Do not make more than two sequential applications. Continue treatment on a 14 to 28 day interval. Globe Artichoke Persimmon Pristine Fungicide

[EPA Reg. No.7969
- 199] WDG 12.8% pyraclostrobin G round, Aerial, or Chemigation 0.18 3 0.55 0 Continue treatment on a 7 to 14 day interval.

Belgium endive Make one app as a spray to roots when brought into cold storage prior to forcing. Apply again at the beginning of forcing after the roots have been packed in forcing trays Prior to cold

storage: 0.013 lb ai/1000 lb roots 1 19 Prior to Cold Storage: make one app as a spray to the roots as they move along a conveyor belt used to bring the roots from field transportation into cold storage bins. Prior to forcing: 0.014 lb ai/70ft2 of forcing tray 1 Prior to Forcing: make one app as a spray to roots at the beginning of forcing, after they have been packed into forcing trays.

Gr eenhouse tomatoes Pagent® Fungicide

[EPA Reg
. No.7969
- 251] WDG 12.8% pyraclostrobin Chemigation, Gr ound, or Handheld spray equipment 0.18 lb ai/A or 0.0018 lb ai/gal 3 0.55 0 For commercial production : Apply as a foliar spray in a minimum of 100 gal/A water volume. Allow at least 7 days between applications. Do not make more than one application before alternations to a fungicide with a different mode of action for at least on application

### Page 17 of 58

**Table 3.3. Use Profile for Proposed Pyraclostrobin Uses**  **Proposed Use**  **Product Formulation**

**[EPA Reg. No.] Application**  **Equipment Max. Single** 

**Applic. Rate (lb ai/A** **) Max.** 

**No. Applic.**  **Per Season**  **Max.**

**Seasonal Applic.**  **Rate (lb ai/A/yr** **) PHI** 

**(days) Use Directions and** 

**Lim itations** 

0. 14 lb ai/A or 0.0014 lb ai/gal 0.42 NA For tomato transplants grown for the home consumer market : Do not exceed 100 gal/A spray volume. Allow at least 7 days between applications. Do not use in transplant production for commercial field
- grown tomatoes. Do not apply more than 2 consecutive applications in any crop production cycle.

Residential fruit and nut trees Bonide® Fruit Tree Spray

Concentrate (FT09) [EPA Reg. No.4
- UII] SC 3.06% pyraclostrobin Handheld spray equipment 0.0041 lb ai/gal

0.0000028 lb ai/ft2 0.12 lb ai/A Pome

and Tree nuts: 4 Stone: 5 Pome: 21 Stone: 14 Almon ds: 25 Tree Nuts: 14 Apply thoroughly as a foliar cover spray to both sides of plant leaves and surfaces. Spray leaf surfaces to the point of drip but do not exceed 2 fl oz of product per 1,500ft2

Residential ornamentals Homeowner Garden Spray

Fungicide [EPA Reg. No. 7969
- GLG] SC 9.0% pyraclostrobin Handheld spray equipment 0.0016 lb ai/gal

0.16 lb a/A 1 6 NA For manual spray applications: spray until foliage is wet. For hose
- end sprayers: typically hose
- end applicators are designed to deliver the desired dial setting per gallon of water in 30 seconds. Retreatment interval is 14 days. 1 Assumed 100 gallons treats 1 acre based on other similar labels; HED recommends that the Homeowner Garden Spray Fungicide (EPA Reg No. 7969
- GLG) label should be clarified by including the spray volume (i.e., number of gallons of spray treated per acre). This information is needed so that the application rate can be presented in terms of lbs ai/A as well as, lbs ai/gal (which is currently on the label). 

### 3.4 **Anticipated Exposure Pathways** The Registration Division has requested an assessment of human health risk to support proposed new use s of p yr aclostrobin on the following: 1) agricultural crops sugarcane, artichoke, Belgium endive, and persimmon; 2) greenhouse tomato use for commercial production and for tomato transplants grown for the home consumer market ; 3) residential fruit and nut trees ; and 4) residential ornamentals and landscape gardens
. Humans may be exposed to py

raclostrobin in food and drinking water, since py ra clostrobin may be applied directly to growing crops and application may

result in py

raclostrobin reaching surface and ground water. There are residential

### Page 18 of 58

uses of p yra clostrobin so there is exposure to residential handlers and those entering treated areas following application. In occupational settings, applicators may be exposed while handling py raclostrobin . 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 py ra clostrobin . This risk assessment considers all of the aforementioned exposure pathways based on the proposed new uses of p yr aclostrobin , but also considers existing uses of p yr ac lostrobin , particularl y in the dietary and residential exposure assessment s . **3.5 Consideration of Environmental Justice**  Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low - Income Populations," (http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf
. As a part of every

pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well
- established procedures. In line with OPP policy, HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consumption, and activities in and around the home that involve pesticide use in a residential setting. Extensive data on food consumption patterns are compiled by the 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 registered 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, spec ialized 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 evaluated. 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 patterns among specific subgroups. **4.0 Hazard Characterization and Dose**  **- Response Assessment**  Py raclo strobin , a strobilurin fungicide, blocks f ung al growth by disrupting mitochondrial respiration through inhibiting Complex III electron transfer at the Cy tochrome bc1 (ubiquinol oxidase) Q 0 

### site. There are no mammalian molecular data to specificall y show this mode of action in the test animals. **4.1 Toxicolog** **y Studies Av**  **ailable for Analysis** The py ra clostrobin toxicity database is complete. The toxicity studies available for risk assessment include an acute toxicity battery ; subchronic toxicity studies (oral, dermal, and inhalation) in rats, dogs or rabbits ; chronic toxi city studies in dogs and rats ; carcinogenicity studies in mice and rats ; developmental toxicity studies in rats and rabbits ; a 2
- generation

### Page 19 of 58

reproduction study in rats ; a battery of mutagenicity

studies ; acute neurotoxicity studies in the rat ; metabolism studies in rats ; in vivo dermal penetration studies in rats, and an immunotoxicity study in mice. **4. 2**  **Absorption, Distribution, Metabolism and Excretion (ADME)** The available ADME data in rats indicated that orally
- administered radiolabeled p yraclostrobin exhibits fast yet modest absorption, broad distribution with no specific tissue accumulation, extensive metabolism, and fast body clearance. There was no evidence of bioaccumulation. The data collected in male and non
-pregnant female rats at two different dose levels (5 and 50 mg/kg) suggest a time to peak plasma levels (tmax

### ) of 8.0/0.5 hrs [M/F] with absorption of 35% of the orall y administered dose (AD). The plasma elimination half
- life (t 1⁄2

### ) was biphasic at the low
- dose with the initial t 1⁄2 

### of 9.0/10.5 hrs [M/F] and the terminal t 1⁄2 

### of 37.5/31.6 hrs [M/F]; at the high
- dose the t 1⁄2 

### was 20.7/19.7 hrs [M/F]. Py raclostrobin was rapidl y and widely distributed in tissues. The highest levels of radioactivity were measured in the liver, thy roid, kidney , lungs, adrenal glands, and pancreas; radioactivity was higher in females than in males. Py raclostrobin levels in the tissues decreased substantially over the first 24 hours and was essentially complete after 72 hours; feces was the primary route of e limination (>79% AD). There were no significant dose
- or sex - dependent differences in tissue distribution or route of elimination. Py raclostrobin was extensively metabolized, resulting in 33 metabolites, in both male and female rats. Py raclostrobin under

went phase
- I reactions such as N
- demethoxylation, various hydrox yl ations, and cleavage of the ether bond with subsequent oxidation; these reactions were followed b y phase II glucuronidation and sulfation. The most abundant metabolite was 500M08 which re sulted from N
- demethoxylation and hydroxylation of the p yr azol ring. The parent was quantified along with an N
- demethyl ated metabolite and was less than 14% AD. **4.2.1 Dermal Absorption**  The Agency

evaluated an available dermal penetration study, but it was deemed initially unacceptable due to material on the dressings being unavailable for absorption. In2003 however, the H ED re - evaluated the study and derived a dermal penetration rate o f 14% (TXR# 0051553; 10 FEB 2003). **4.3 Summary of Toxicological Effects**  The most consistently

observed effects of py

raclostrobin exposure across species, genders, and treatment durations were diarrhea and decreased body weight, body weight gain , and f o od consumption
. P yraclostrobin also causes intestinal disturbance as indicated by increased incidence of diarrhea or duodenum mucosal thickening. These intestinal effects appeared to be related to the irritating action on the mucus membranes as demonstrated b y irritation seen in the primary eye irritation study
. In the rat acute and subchronic neurotoxicity studies, neuropathology

and behavior changes were not observed.

### Page 20 of 58

In the rat and rabbit developmental toxicity studies, developmental toxicity (i.e. skeletal variations, post
- implantation loss, and fetal resorption) occurred at doses greater than or equal to those doses causing maternal toxicity (i.e. diarrhea , decreased body weight , body weight gain , food consumption, and clinical signs of toxicity)
. In the reproduction studies (guideline and range - finding studies), s ystemic toxicity manifested as decreased body weight and body weight gain in both the parents and offspring ; no reproductive toxicity was seen. Py raclostrobin was classified by the Canc er Assessment Review Committee (CARC) as “Not Likel y to be Carcinogenic to Humans” based on the lack of treated related increase in tumor incidence in adequatel y conducted carcinogenicity studies in rats and mice (CARC 01 FEB 2007). Py

raclostrobin did not cause mutagenicity or genotoxicity in the in vivo and in vitro assays nor did it cause immunotoxicity in T
- cell dependent antibody response (TDAR) assays in mice with preliminary

review. Py raclostrobin has moderate to low acute toxicity via the oral, der mal, and inhalation routes of exposure ( Toxicity

Categories II
- IV). Py

raclostrobin is not a dermal sensitizer. However, py raclostrobin was determined to have a low effect dermal and eye irritant ( Toxicity Category III)
. **4.4 Safety Factor for Infants and**  **Children (FQPA Safety Factor)** For all assessment scenarios, the default 10X FQPA Safety Factor can be reduced to 1X because the toxicity

database is complete and there is no neurotoxicity, and no residual uncertainty in the exposure data. Although there are indications of qualitative susceptibility, the points of departure are protective of the effects in the developing organism. **4. 4**  **. 1**  **Completeness of the Toxicology Database** The toxicology

database is complete, acceptable, and sufficient for assess ing susceptibility to infants and children as required by FQPA. **4.4.2 Evidence of Neurotoxicity**  There are no indications in any of the studies available that the nervous s ys tem is a target for py raclostrobin
. Effects seen in the acute and subchronic neurotoxicity studies in rats are considered to reflect perturbations in mitochondrial respiration leading to effects on energy production. In the absence of frank neurotoxicity or neuropathology

findings in the neurotoxicity battery or elsewhere in the database, a developmental neurotoxicity study is not required. **4. 4**  **.3 Evidence**  **o f Sensitivity/Su**  **sceptibility in the Developing o r Young Animal**  There is no evidence that py raclostrobin results in increased susceptibility in in utero rats or rabbits in the prenatal developmental studies or in young rats in the 2
- generation reproduction

### Page 21 of 58

study . Although there is qualitative evidence of increased susceptibility in the prenatal development study

in rabbits, HED did not identify any residual uncertainties after establishing toxicity endpoints and traditional UFs to be used in the risk assessment of py raclostrobin. The degree of concern for prenatal and/or postnatal toxicity is low. **4. 4**  **.4 Residual**  **Uncertainty in the Expo sure Datab**  **ase** There are no residual uncertainties identified in the exposure databases. The acute dietary exposure assessments were performed assuming 100% of the crop s were treated with py raclostrobin and tolerance
- level or highest field trial residues. The chronic dietary exposure assessments were performed us ing average percent crop treated estimates and tolerance
- level or highest field trial residues. EPA made conservative (protective) assumptions in the ground and surface water modeling used to assess exposure to py raclostrobin in drinking water. EPA used similarly conservative assumptions to assess post
- application exposure of adults and children as well as incidental oral exposure of children
. The residential expo sure assessment is based on the updated 2012 Residential SOPs employing surrogate study data, including conservative exposure assumptions based on Day 0 dermal/oral contact to turf and surfaces treated at the maximum application rate. These data are relia ble and are not expected to underestimate risks to adults or children. The Residential SOPs are based upon reasonable “worst
- case” assumptions are not expected to underestimate risk. Although some of the residue values used in the dietary exposure assess ment were refined, th ese assessments will not underestimate the exposure and risks posed by

p yr aclostrobin
. **4. 5**  **Toxicity Endpoint and Point of D**  **eparture Selections 4.5.1**  **Dose -**  **Response Assessment** A variety of oral toxicity

studies were used for the different risk assessment scenarios including the rabbit developmental toxicity study , the acute neurotoxicity study in rats, the rat carcinogenicity

study , and the 13
- week study in dogs. In addition, the 28
- day inhalation study

in rats will now be used f

or short
- and intermediate
- term occupational and residential inhalation risk assessments. The endpoints in these studies are well characterized and are the most sensitive among available comparable toxicity studies in other species. All dietary endpoints (i.e., acute and chronic RfDs), are calculated from the respective study ’s NOAEL after applying a 100
- fold safety factor (10 X to account for interspecies extrapolation and 10X for intraspecies variation). For all other scenarios, including dermal, inhal ation, and incidental oral, an MOE approach will be used with a Level of Concern (LOC) at 100. The selected endpoint from the acute neurotoxicity study of 300 mg/kg/day

for the acute dietary (general population) risk assessment is appropriate because the decreased body weight gain in males occurred during the first week after a single oral high dose of 1000 mg/kg. The rabbit developmental toxicity study findings are used for endpoint selections for acute dietary (Females 13+) as well as for short
- and intermediate
- term dermal exposures. For the acute dietary

endpoint (Females 13+), the rabbit developmental findings of increased resorptions/post
- implantation loss at the LOAEL of 10 mg/kg/day are assumed to occur

### Page 22 of 58

following a single in utero exposure. The se effects were dose
- dependentl y increased at the next (high) dose of 20 mg/kg/day
. The same study and developmental endpoint are used for short
and intermediate
- term dermal exposures after applyinga dermal absorption factor of 14%. Additionally , the m aternal endpoints of decreased body weight gain and decreased food intake and food efficiency

were found at the LOAEL of 10 mg/kg/day
. This selection mitigates any concern from the observed developmental toxicity findings in rabbits which are not assessed in the rat dermal toxicity

study
. The rat carcinogenicity

study findings are used for endpoint selections for chronic dietary and dermal exposures based on findings of decreased body weight/gain and kidney

tubular casts/atrophy in both sexes in addition to liver necrosis and stomach lesions in males at the high dose (LOAEL) of 9.2 mg/kg/day
. This study has the lowest NOAEL (3.4 mg/kg/day) in the most sensitive species following chronic exposure. The dermal absorption factors of 14% will be applied to th e dermal long
- term risk scenario. The short
- and intermediate
- term in cident oral exposures are from the s ubchronic toxicity study in the dog , and are based increased incidence of diarrhea, clinical chemistry changes, duodenum mucosal hy

pertrophy , and decreased body weight and food intake/efficiency at a LOAEL of 12.9 mg/kg/day , with an o ral NOAEL of 5.8 mg/kg/day
. The short
- , intermediate
- , and long
- term inhalation exposures are based on the 28
- day inhalation toxicity study in rats which had dose
- dependent adverse findings in the respiratory s ys tem and duodenum. The study ’s oral equivalents NOAEL/LOAEL are 0.23/6.92 mg/kg/day (corresponding to study’s air concentration of 0.001/0.03 mg/Lair). The findings are well characterized in that the severity, frequency, and location (e.g., along the respiratory tract) are dose
- dependent ranging from no effects at the NOAELof 0.001 mg/Lair to severe respiratory effects and death at the highest dose of 0.3 mg/L air. **4.5.2 Recommendation for Combining Routes of Exposure for Risk Assessment**  As per FQPA, 1996, when there are potential residential exposures to a pesticide, aggregate risk assessment must consider exposures from three major s ources: oral, dermal and inhalation exposures. When common toxicity endpoints are selected for these routes of exposure they may be aggregated. Aggregate assessments are required for acute and chronic dietary (food + water) exposures, and short
- term resi dential exposures (i.e., chronic dietary plus incidental oral and dermal exposures). Residential short
- /intermediate
- term dermal exposure for adults and toddlers were assessed using the NOAEL (5 mg/kg/day) from the rabbit developmental study . While the developmental effect of increased resorptions is not applicable to toddlers, it should be noted that the maternal NOAEL from this study

is also 5 mg/kg/day , and is based on reduced body weight gain, food consumption, and food efficiency at the LOAEL of 10 m g/kg/day ; this more relevant endpoint was used to assess toddler dermal exposure. For incidental oral ingestion, exposure was assessed using the endpoint from a 13
- week feeding study in the dog. The NOAEL from this study is 5.8 mg/kg/day , based on increa sed incidence of diarrhea, clinical chemistry changes, duodenum mucosal hy

pertrophy , and decreased body weight and food intake/efficiency at the LOAEL of

### Page 23 of 58

12.9 mg/kg/day . A common effect (i.e., decreased body weight gain, food intake, and food efficiency) was seen in the studies selected to evaluate toddler dermal and incidental oral ingestion exposure; therefore, route
- specific MOEs were aggregated for toddlers. **4.5.3 Cancer Classification and Risk Assessment Recommendation**  Py raclostrobin was classified by the Cancer Assessment Review Committee (CARC) as “Not Likel y to be Carcinogenic to Humans” based on adequate carcinogenicity and mutagenicity studies (CARC 01 FEB 2007). **4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk**  **As sessment**  **Table 4.5.4.1 :**  **Summary of Toxicological Doses and Endpoints for use in Dietary and Non -**  **Occupational Human Health**

**Risk Assessments Exposure Scenario**  **Point of**

**Departure (P o**  **D) Uncertainty /** 

**FQPA Safety Factors**  **RfD, PAD, Level**

**of Concern for Risk**  **Assessment Study and Toxicological Effects**  Acute Dietary General population ( including infants and children) N OAEL = 3 0 0 mg/kg/day UF A = 10x

UF H = 10x FQPA = 1 x aRfD =

3.0 mg/kg/day aPAD = 3.0 mg/kg/day Acute Neurotoxicity

– Rat

LOAEL = 1000 mg/kg/day based on decreased body weight gain in males.
Acute Dietary, Females (13
- 49 years old) N OAEL = 5.0 mg/kg/day UF A = 10x

UF H = 10x FQPA = 1 x aRfD =

0.05 mg/kg/day aPAD = 0.05 mg/kg/day Developmental Toxicity

– Ra bbi t LOAEL = 10.0 mg/kg/day based on developmental toxicity findings of increased resorptions. Chronic Dietary NOAEL = 3.4 mg/kg/day UF A = 10x

UF H = 10x FQPA = 1x c RfD =

0.034 mg/kg/day cPAD = 0.034 mg/kg/day Carcinogenicity

– Rat

LOAEL = 9.2 mg/kg/day based on decreased body weight/body weight gain, kidney tubular casts and atrophy in both sexes; increased incidence of liver necrosis and erosion/ulceration of the glandular
- stomach and fore
stomach in males. Incidental Oral Short Term (1
- 30 days) Intermediate Term (1
- 6 mo nths) Oral N OAEL = 5.8 mg/kg/day UF A = 10x

UF H = 10x FQPA = 1 x Residential LOC

for MOE = 100 Subchronic Toxicity

– Dog

LOAEL = 12.9 mg/kg/day based on increased incidence of diarrhea, clinical chemistry changes, duodenum mucosal hypertrophy, and decreased body weight and food intake/efficiency. Dermal Short Term (1
- 30 days) Intermediate Term (1
- 6 months) Oral N OAEL = 5.0 mg/kg/day (Dermal Absorption Rate = 14%) UF A = 10x

UF H = 10x FQPA = 1 x Residential LOC

for MOE = 100 Developmental Toxicity

– Ra bbi t LOAEL = 10.0 mg/kg/day based on developmental toxicity findings of increased resorptions and maternal toxicity based on decreased body weight gain and decreased food intake/efficiency.

### Page 24 of 58

**Table 4.5.4.1 :**  **Summary of Toxicological Doses and Endpoints for use in Dietary and Non -**  **Occupational Human Health**

**Risk Assessments Exposure Scenario**  **Point of**

**Departure (P o**  **D) Uncertainty /** 

**FQPA Safety Factors**  **RfD, PAD, Level**

**of Concern for Risk**  **Assessment Study and Toxicological Effects**  Dermal Long Term (>6 months) Oral NOAEL =

3.4 mg/kg/day (Dermal Absorption Rat = 14%) UF A = 10x

UF H = 10x FQPA = 1 x Residential LOC

for MOE = 100 Carcinogenicity

– Rat

LOAEL = 9.2 mg/kg/day based on decreased body weight/body weight gain, kidney tubular casts and atrophy in both sexes; increased incidence of liver necrosis and erosion/ulceration of the glandular
- stomach and fore
stomach in males. Inhalation Short Term (1
- 30 days) Intermediate Term (1
- 6 months) Long Term (>6 months) N OAEL =

0.23 mg/kg/day (Air Concentration = 0.001 mg/L) UF A = 10x

UF H = 10x FQPA = 1 x Residential LOC

for MOE = 100 Inhalation Toxicity

– Rat

LOAEL = 6.9 mg/kg/day (air concentration = 0.03 mg/L) based on duodenum mucosal hyperplasia and respiratory system findings including alveolar histiocytosis and olfacto ry atrophy/necrosis in nasal tissue.
Cancer (oral, dermal, and inhalation) Classification: “Not likely to be Carcinogenic to Humans” based on the absence of significant tumor

increases in two adequate rodent carcinogenicity studies. Point of Departure (P o D) = 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). 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 4.5.4.2 :**  **Summary of Toxicological Doses and Endpoints for use in Occupational Human Healt h Risk Assessments**  **Exposure Scenario Point of** 

**Departure (P o**  **D) Uncertainty /** 

**FQPA Safety Factors**  **Level of**

**Concern for Risk Assessment**  **Study and Toxicological Effects** Dermal Short Term (1
- 30 days) Intermediate Term (1
- 6 months) Oral N OAEL = 5.0 mg/kg/day (Dermal Absorption Rate = 14%) UF A = 10x

UF H = 10x FQPA = 1 x Residential LOC

for MOE = 100 Developmental Toxicity

– Ra bbi t LOAEL = 10.0 mg/kg/day based on developmental toxicity findings of increased resorptions and maternal toxicity based on decreased body weight gain and decreased food intake/efficiency. Dermal Long Term (>6 months) Oral NOAEL =

3.4 mg/kg/day (Dermal Absorption Rat = 14%) UF A = 10x

UF H = 10x FQPA = 1 x Residential LOC

for MOE = 100 Carcinogenicity

– Rat

LOAEL = 9.2 mg/kg/day based on decreased body weight/body weight gain, kidney tubular casts and atrophy in both sexes; increased incidence of liver necrosis and erosion/ulceration of the glandular
- stomach and fore
stomach in males. Inhalation Short Term (1
- 30 days) Intermediate Term N OAEL = 0.23 mg/kg/day (Air Concentration = UF A = 10x

UF H = 10x FQPA = 1 x Residential LOC

for MOE = 100 Inhalation Toxicity

– Rat

LOAEL = 6.9 mg/kg/day (air concentration = 0.03 mg/L) based on duodenum mucosal hyperplasia and respiratory system findings including

### Page 25 of 58

**Table 4.5.4.2 :**  **Summary of Toxicological Doses and Endpoints for use in Occupational Human Healt h Risk Assessments**  **Exposure Scenario Point of** 

**Departure (P o**  **D) Uncertainty /** 

**FQPA Safety Factors**  **Level of**

**Concern for Risk Assessment**  **Study and Toxicological Effects** (1
- 6 months) Long Term (>6 months) 0.001 mg/L) alveolar histiocytosis and olfactory atrophy/necrosis in nasal tissue.
Cancer (oral) Classification: “Not likely to be Carcinogenic to Humans” based on the absence of significant tumor

increases in two adequate rodent carcinogenicity studies. Point of Departure (P o D) = 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). FQPA SF = FQPA Safety Factor. 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 R ationale**  The residues of concern for dietary risk assessment and the tolerance expression are summarized in Table 5.1 (HED MARC, DP278044, L . Cheng, 10/9/01)
. HED has concluded that the residues of concern in plants include py raclostrobin and its desmethox y metabolite (BF 500
- 3) for purposes of tolerance enforcement and risk assessment. For livestock commodities, HED has determined that for purposes of tolerance setting and risk assessment the residues of concern consist of py

raclostrobin and its metabolites convertible to 1
- (4
- chlorophenyl)
- 1 H
-py razol
- 3
- ol (BF 500
- 5) and 1
- (4
- chloro
- 2
- hydrox yphenyl )
- 1 H
-py razol
- 3
- ol (BF 500
- 8). For drinking water, the resid u e of concern for p yr aclostrobin is the parent only
. **Table 5.1. Summary of Metabolites an**  **d Degradates to be included in the Risk Assessment and Tolerance Expression**  **. Matrix**  **Residues included in Risk Assessment**  **Residues included in Tolerance Expression**  Plants Primary Crop parent, BF 500
- 3 parent, BF 500
- 3

Rotational Crop parent, BF 500
- 3 parent, BF 500
- 3 Livestock Ruminant parent, BF 500
- 5, BF 500
- 8 parent, BF 500
- 5, BF 500
- 8

Poultry parent, BF 500
- 5, BF 500
- 8 parent, BF 500
- 5, BF 500
- 8 Drinking Water p arent only Not Applicable 

### 5 **.2 Food**  **Residue Profile**  Field trial data on sugarcane (MRID 48237401) , artichoke (MRID 48897401) , Belgium endive (MRID 48897402) , and persimmon (MRID 48897403) have been submitted to support the proposed tolerances. These data are adequate to support dietary risk assessment as well as the proposed tolerance s of py raclostrobin on sugarcane, artichoke, Belgium endive, and persimmon.

### Page 26 of 58

The number and geographic distribution of the field trials are adequate. The anal ytical method was demonstrated to be acceptable via concurrent recoveries of fortified control samples. The intervals of frozen storage of samples are covered by previous storage stability studies, and no corrections for loss of residue are needed. The trials were conducted according to the proposed label s (single and seasonal application rates, PHI) . Summaries of the residue data from the crop field trials are presented in Appendix D, Table D
- 1 through D
- 4. A processing study was submitted for sugarcane (MRID 48237401). The study is adequate. Residues of py

raclostrobin and BF 500
- 3 did not concentrate in blackstrap molasses or refined sugar, relative to the concentration in the raw agricultural commodity (sugarcane). Therefore, tolerances are not necessary for these processed commodities. Greenhouse Grown Tomato Transplants Grown for Home Consumer Market BASF Corporation has requested the addition of greenhouse tomato use for commercial production and for tomato transplants grown for the home consumer market to the PageantTM Fungicide label (EPA Reg. No. 7969
- 251). This product is identical to PristineTM Fungicide ( EPA Reg. No. 7969
- 199), which includes use on greenhouse tomatoes, but does not cover tomato transplants for consumers or use of lath type structures. No residue chemistry data were submitted with this request. Residues on tomato fruits from such use of PristineTM Fungicide ( EPA Reg. No. 7969
- 199) for tomato transplants in green house, lath house, and other production structures would be expected to be less than those found in the greenhouse trials supporting the approved greenhous e use. The existing tolerance for fruiting vegetables will cover the requested new uses of the PageantTM Fungicide ( EPA Reg. No. 7969
- 251) formulation. Residential Use of FT09 (EPA File Sy mbol 4
- UII) on Pome Fruit, Stone Fruit, and Tree Nuts The submitted use directions are sufficient to allow for evaluation of the proposed residential use of FT09 based on comparison to the existing BASF Pristine ® 

### label for agricultural uses. The BASF formulation is a water dispersible granule. It is a solid material that forms a dispersion when mixed with water. The Bonide formulation is a suspension concentrate or suspension of solid materials in water. It also will form a dispersion when mixed with water. The formulations are expected to behave similarly when applied in the same manner (same rate) to crops. The Organization of Economic Cooperation and Development (OECD) Crop Field Trial Guidance recognizes such formulations as yielding the same residues at PHIs greater than 7 days. All relevant Bonide PHIs exceed 7 days, and therefore the resulting residues based on formulation will not be greater than residues from the BASF formulation. The PHIs for the Bonide formulation are equal to or longer/greater than the BASF Pristine® formulation PHI s. Theref ore, residues from use on the Bonide formulation are anticipated to be no more than or less than residues from the BASF formulation, based on comparison of the PHIs. The application rates (lbs ai/A) for the Bonide formulation, both per application and p er season, are approximately

equal to or less than the corresponding application rates for the BASF Pristine® formulation. Therefore, residues from the use of the Bonide formulation are anticipated to be no more than or less than residues from the BASF formulation, based on

### Page 27 of 58

comparison of the application rates. Residential use of the Bonide FT09 per the proposed label will not yield residues in excess of those from agricultural use of the BASF formulation Pristine ® 

### per the approved label. Livestock The livestock feedstuff associated with the proposed uses in th e s e petition s is sugarcane blackstrap molasses
. Sugarcane blackstrap molasses is a carbohydrate concentrate (CC) feed item for dairy

cattle and beef cattle and may comprise up to 10% of the diet of each. The processing factor for conversion of sugarcane to blackstrap molasses is 0.3X (S. Funk, 482374 01.der2). N o significant changes to the dietary burden result from the present considerations. No changes to the existing livestock tolerances are indicated. Additionally , s ugarcane blackstrap molasses is not a poultry or swine feed item. Rotational Crops An adequate confined rotational crop study was reviewed in PP#0F6139 (DP278668, L . Cheng, 11/28/01) . The study

showed that the metabolism of py raclostrobin in rotated crops is similar but more extensive than that in primary crops. P yr aclostrobin undergoes demethoxylation to yi eld BF 500
- 3, followed by further degradation to medium polar and polar metabolites, and subsequent conjugation reactions and incorporation into natural products. The HED MARC has determined that the residues of concern in rotational crops consist of py raclostrobin and metabolite BF 500
- 3. A limited field rotational crop study was reviewed in PP#0F6139. The results indicate that residues of p yr aclostrobin and its metabolite BF 500
- 3 were each less than the method LOQ (<0.02 ppm) in/on rotational crop matrices (radish, roots and tops; cabbage, with and without wrapper leaves; and wheat forage, hay , and grain) planted 14 days following the last of six sequential foliar applications to the primary crop, cucumb ers, of the 2 lb/gal EC formulation at 0.19
- 0.20 lb ai/A/application. Residues of py raclostrobin in/on one sample of wheat straw from the CA test site were at the LOQ (0.02 ppm), but residues of p yr aclostrobin in/on a replicate sample from the same plot were below the LOQ (0.012 ppm) for an average residue of <0.02 ppm. Residues of metabolite BF 500
- 3 were nondetectable (<0.02 ppm) in/on all samples of wheat straw. The registered p yraclostrobin end
- use product labels presentl y specif y a 14
- day

plantback interval restriction for all crops that are not registered. **5.3 Water Residue Profile**  The drinking water residues used in the dietary risk assessment were provided by EFED (D403871, D405066, F. Khan, 04/04/2013 ) and incorporated directl y into th e dietary assessment. Water residues were incorporated in the DEEM
- FCID into the food categories “water, direct, all sources” and “water, indirect, all sources.” For surface water, the EDWCs were generated using EFED’s standard suite of models. Pesticide Root Zone Model (PRZM v3.12.2, May 12, 2005) and Exposure Anal ys is Modeling S ys tem

### Page 28 of 58

(EXAMS v2.98.04.06, Apr. 25, 2005) are simulation models coupled with the input shell PRZM/EXAMS (PE v5.0, Nov. 15, 2006) to generate EDWCs of p yraclostrobin residues that may occur in surface water for drinking water. For ground water, Screening Concentration in Ground Water (SCI
- GROW v2.3, Jul. 29, 2003) is a regression model used as a screening tool to estimate pesticide concentrations found in ground water used as drinking water. In addition, Tier 1 ground water EDWCs for py raclostrobin, resulting from its use on various crops were also derived using the PRZM
- GW model (Pesticide Root Zone Model for Groundwater, version 1.0, August 31, 2012), with the GW
- GUI (Graphical U ser Interface, version 1.0, August 31, 2012). F or the proposed use s of py raclostrobin , the use o n fruiting vegetables resulted in the highest surface water concentrations at 16.6 μg/L for the 1
- 10 year peak value from ground application and at 1.1 μg/L for the 1
- 10 annual year average value from aerial application. The acute and chronic EDWCs resulting from the proposed application uses are lower than the EDWCs for surface water in the previously recommended drinking water assessments for py raclostrobin for turf uses (USEPA 2007 D389729+ )
. Since the EDWCs for surface water for proposed uses are lower than the previously recommended EDWCs for this chemical, the EDWCs for surface water will not supersede the EDWCs previousl y recommended for turf use. Table 5.3 provides a summary of the estimated concentrations of py raclostrobin in surface water. In the acute anal ys is, the 1
- in
- 10 year peak surface water value of 35.6 ppb was used and in the chronic analysis the surface wat er value of 2.3 ppb was used. Estimates of py raclostrobin concentration in drinking water were less for ground water sources. The models and their descriptions are available at the EPA internet site: http://www.epa.gov/oppefed1/models/water/
. **Table 5**  **. 3.**  **EDWCs of Pyraclostrobin Crop Scenario**  **PRZ M/EXAMS Estim**  **ated Concentrations in Surface Water (**  **g/L) Acute**  **1 (μg/L)**  **Chronic (μg/L)** Surface Water NJ Nursery (no irrigation) Turf 35.6 2.3 Ground W ater2 N/A 0.0 6 0.02 1 These are the highest EDWCs for previously evaluated use scenarios and the estimated acute and annual average surface water concentrations were 35.6 and 2.3 μg/L respectively. Previously estimated ground water concentrations for acute was 0.02 μg/L 2007, D389729
. 2 EDWCs based on PRZM
- GW model 

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

exposure analysis incorporates all current and proposed tolerances for residues of py raclostrobin, including its metabolites and degradates. A slightly refined acute dietary

exposure assessment was perfo r med for p yr aclostrobin. The anal ys is used tolerance
- level residues or highest field trial residues and empirical or default processing factors. Experimentally derived processing factors were used for fruit juices, tomato, sugarcane, and wheat commodities . For all other processed commodities, DEEM default

### Page 29 of 58

processing factors were assumed. Estimated drinking water concentrations (EDWCs) were also used
. The estimated acute drinking water concentration for p yr aclostrobin ( 0.0356 ppm) was calculated based on a turf scenario for surface water. A refined chronic dietary anal ys is was conducted for this assessment , since some refinement was needed for the aggregate assessment. The chronic dietary anal ys is included tolerance
- level or average field trial residues, average percent crop treated estimate s (2012) when available , and empirical processing factor s. Screening level estimates of agricultural uses of py raclostrobin were provided by

the Biological & Economic Analysis Division (BEAD). Experimentally derived processing fa ctors were used for fruit juices, tomato, sugar cane, and wheat commodities
. For all other processed commodities, DEEM default processing factors were assumed. The estimated drinking water concentration for py raclostrobin ( 0.0023 ppm) was calculated based on a turf scenario for surface water. Py ra clostrobin is classified as “no t likel y to be carcinogenic to humans”
. Therefore, a cancer dietary exposure assessment was not conducted. **5.4.2 Percent Crop Treated Used in Dietary Assessment**  The acute dietary

assessment was based on 100% crop treated (%CT). BEAD provided updated percent crop treated information for py raclostrobin ( S. Haddad, 11/18/2012 ). For the chronic anal ys es, average %CT was incorporated
. One hundred percent crop treated was assumed for commodities with no %CT information , including sugarcane and Belgium endive
. The following average percent crop treated estimates were used in the chronic dietary risk assessments for the crops that are currentl y registered for p yr aclostrobin: almonds 40%; apples 15%; apricots 25%; barley 10%; green beans 5%; blueberrie s 45%; broccoli 5%; cabbage 10%; can eberries 50% ; cantaloupes 15%; carrots 35%; cauliflower 2.5%; celery 2.5%; cherries 50%; corn 10%; cotton 2.5%; cucumber 5%; dry beans/peas 10%; garlic 15%; grapefruit 25%; grapes 30%; hazelnuts (filberts) 15%; lemons 2. 5%; lettuce 5%; nectarines 10%; onions 20%; oranges 5%; peaches 20%; peanuts 25%; pears 15%; green peas 5%; pecans 2.5%; peppers 10%; pistachios 30%; plums/prunes 5%; potatoes 15%; pumpkins 20%; soy beans 5%; spinach 5%; squash 15%; strawberries 65%; sugar beets 45%; sweet corn 5%; tangelos 15%; tangerines 10%; tomatoes 25%; walnuts 1%; watermelons 30%; wheat 5%. **5.4.3 Acute Dietary Risk Assessment**  The results of the acute dietary anal ys is for food and drinking water indicate that acute dietary risks are not of concern ( < 100% of the aPAD) for the U.S. population and all subgroups. Combined dietary exposure from food and drinking water at the 95 th 

### percentile of exposure for the U.S. population is equivalent to 1.5% of the acute Population Adjusted Dose (aPAD). The population subgroup with the highest estimated acute dietary exposure to py

raclostrobin is females 13
- 49 years, with an estimated exposure of 8 7 % of the aPAD at the 95 th 

### percentile
.

### Page 30 of 58

**5.4.4 Chronic Dietary Risk Assessment**  **s** The results of the refined chronic dietary (food and drinking water) anal ys is are below the Agency ’s level of concern for all population subgroups. The dietary exposure for food and drinking water for the general U.S. population is 8. 0 % of the chronic Population Adjusted Do se (c PAD) and 2 7 % of the cPAD for children 1
- 2 years old , the population subgroup with the highest estimated chronic dietary exposure to py

raclostrobin. **5.4. 5**  **Summary Table Table**  **5.4.5 . Summary of Dietary Exposure and Risk for Pyraclostrobin Food & Drin**  **king Water.**

**Population Subgroup Acute Dietary**  **(95th Percentile) Chronic Dietary**  **Dietary Exposure (m**  **g/kg/day) % aPAD**  **Dietary Exposure (m**  **g/kg/day) % cPAD**  General U.S. Population 0.044721 1.5 0.002707 8.0 All Infants (< 1 year old) 0.061716 2.1 0.004353 13 **Children 1 -**  **2 years old** 0.083049 2.8 **0.009206 27**  Children 3
- 5 years old 0.074666 2.5 0.006204 18 Children 6
- 12 years old 0.044251 1.5 0.003525 10 Youth 13
- 19 years old 0.031506 1.0 0.001832 5.4 Adults 20
- 49 years old 0.041724 1.4 0.002224 6.5 Adults 50
- 99 years old 0.041722 1.4 0.002252 6.6 **Fem ales 13**  **- 49 years old**  **0.043481 87**  0.002005 5.9 

### *The subpopulations with the highest risk estimates are bolded. **6.0 Residential (Non**  **- Occupational) Exposure/Risk Characterization**  The proposed residential uses for p yr aclostrobin will result in residential handler and post
application exposures. In addition, the existing use on residential turf (Insignia Fungicide label; EPA Reg. No. 7969
- 184) was reassessed in this document to refl ect updates to HED’s 2012 Residential SOPs 2 

### along with policy changes for body

weight assumptions , since the revisi on s to these exposures could impact the human health aggregate risk assessment for py raclostrobin. Registered and proposed products do not l ead to any residential handler or post
- application risk estimates of concern.

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

### Page 31 of 58

**6.1 Residential Handler Exposure**  The residential handler assessment includes short
- term exposures via the dermal and inhalation routes. Exposures occur from treating gardens, trees, and turf. HED’s LOC for the MOE is defined b y the uncertainty factors that are applied to the assessment. HED applies a 10X factor to account for variability among species and a 10X factor to account for variability within species. The total uncertainty factor that has been applied to the non
- cancer assessment of p yra clostrobin is 100X for residential exposure. Residential exposure and risk resulting in MOEs greater than or equal to 100 will not be of concern to HED (LOC = 100). Summaries of the inhalation and dermal risk estimates for residential handlers are included in Table 6.1
. The maximum application rate for each exposure scenario is presented as the worst case scenario. The residential handler dermal MOEs range from 740 (hose end turf application of WDG formulation) to 13 ,000 (hose end sprayer application to trees using a liquid formulation). The residential handler inhalation MOEs range from 5 9 0 ( manually pressurized handwand turf application of WDG formulation) to 3,400 ,000 (hose end sprayer application to trees using a liquid formulation). The dermal and inhalation risks to handlers are not of concern to HED for any of the residential handler scenarios.

### Page 32 of 58

**Table 6.1. Residential Handler Non -**  **cancer Exposure and Risk Estimates for Pyraclostrobin. Exposure Scenario**  **Level of Concern**  **Dermal**

**Unit Exposure**  **(m g/lb ai)**  **Inhalation**

**Unit Exposure**  **(m g/lb ai)**  **Ma xim**  **um**

**Application Rate 1**  **Area Treated or Am**  **ount Handled Daily**  **2 Dermal**  **Inhalation**

**Dose (m** **g/k g/day)**  **3 MOE**  **4 Dose**  **(m g/k** **g/day) 5**  **MOE 6**  Mixer/Loader/Applicator Liquid Garden/Trees : manually pressurized handwand 100 63 0.018 0.0041 lb ai/gal 5 gal 0.0026 1,900 0.0000046 50,000 Liquid Garden/Trees : manually pressurized handwand 100 63 0.018 0.0000028 lb ai/ft2 1200 ft2 0.00043 12,000 0.00000076 300,000 Liquid Garden/Trees : hose
- end sprayer 100 58 0.0014 0.0000028 lb ai/ft2 1200 ft2 0.00040 13,000 0.000000059 3,900,000 Liquid Garden/Trees : hose
- end sprayer 100 58 0.0014 0.0041 lb ai/gal 11 gal 0.0053 940 0.00000079 290,000 Liquid Garden/Trees : backpack sprayer 100 130 0.14 0.0000028 lb ai/ft2 1200 ft2 0.00089 5,600 0.0000059 39,000 Liquid Garden/Trees : backpack sprayer 100 130 0.14 0.0041 lb ai/gal 5 gal 0.0054 920 0.000036 6,400 Liquid Garden/Trees : sprinkler can 100 58 0.0014 0.0000028 lb ai/ft2 1200 ft2 0.00040 13,000 0.000000059 3,900,000 Liquid Garden/Trees : sprinkler can 100 58 0.0014 0.0041 lb ai/gal 5 gal 0.0024 2,100 0.00000036 640,000 WDG Lawn/turf : manually pressurized handwand 100 69 1.1 0.0057 lb ai/gal 5 gal 0.0040 1,300 0.00039 590 WDG Lawn/turf : hose
- end sprayer 100 13.4 0.022 0.5 lb ai/A 0.5 A 0.0068 740 0.000069 3,300 WDG Lawn/turf : backpack sprayer 100 69 1.1 0.0057 lb ai/gal 5 gal 0.0040 1,300 0.00039 590 WDG Lawn/turf : sprinkler can 100 13.4 0.022 0.000011 lb ai/ft2 1000 ft2 0.00031 16,000 0.0000032 73,000 1 Based on the proposed garden/tree use on Bonide FT09 label (EPA Reg. No. 4
- UII) and registered turf use on I nsignia® Fungicide label (EPA Reg. No. 7969
- 184). 2 Based on HED’s 2012 Residential SOPs (http://www.epa.gov/pesticides/science/residential
- exposure - sop.html). 3 Dermal Dose = Dermal Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A/day or gallons/day) × Dermal Absorption Factor (%) ÷ Body Weight (kg). 4 Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day). 5 Inhalation Dose = I

nhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A/day or gallons/day) ÷ BW (kg). 6 Inhalation MOE = I

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

### Page 33 of 58

**6.2 Post**  **- Application Exposure**  There is the potential for post
- application exposure for individuals as result of being in an environment that has been previously treated with py

raclostrobin. Short
- term dermal exposures were assessed for adults, youth 11 to 16 years old, and children 6 to 11 years old. Short
- term dermal and incidental oral exposures were assessed for children 1 to <2 ye ars old. A series of assumptions and exposure factors served as the basis for completing the residential post
application risk assessment. Each assumption and factor is detailed in the 2012 Residential SOPs 6



### . Dislodgeable Foliar Residues Chemical
- specific 

### dislodgeable foliar residue (DF R) data were previously submitted by

the registrant to support earlier registration requests for food crops. An overvi ew of each study was provided in a previous assessment (D269670, K. O’Rourke, 9/30/2002 ). 

### Py raclostrobin DFR studies were conducted on peaches, peanuts, strawberries, grapes
. The Canadian Pesticide Management Regulatory

Agency (PMRA) performed the primary review of these data , and considered the results useful for risk assessment purposes; summaries of their reviews and a summary of the DFR study results is provided in a previous HED assessment ( D269670, K. O’Rourke, 9/30/2002 )


### . It should be noted that PMRA only used the DFR data to calculate % dissipation per day and half
lives. Therefore, HED went back to the initial study to calculate the DFR on day zero based on the results of the D F R study . The calculated DFR values on day zero were used in the post - application dermal assessments. The PA peach DFR data, which resulted in the highest DFR values of the three study sites, were used in the residential fruit/nut tree and garden assessment s . The CA strawberry DF R data, which also resulted in the high est DFR values of the three study sites, were used in the residential exposure to retail tomato transplants. The DFR data used in this assessment are presented in Appendix F, Tables F
- 1 through F
- 3. 

### Turf Transferable Residues Turf transferrable residue (TTR) data (MRID 45118725) are available from an earlier submission in support of a request for use on golf course turf. This study was not used in the previous turf exposure assessments because the study used an emulsifiable co ncentrate formulation, rather than the water dispersible granule formulation that is currently registered. The effect of formulation ty

pe on residue values can be significant. At that time, HED concluded that using the results from the TTR study may be under protective due to formulation effects (D298017, K. O’Rourke, 8/19/200 4)


### . However, HED has since determined that there is no statistical difference between residues resulting from liquid, wettable powder (applied as a spray), or water dispersible granular (applied as a spray) applications. Therefore, the residue data from the py raclostrobin
specific TTR study were used in this assessment ( 2012 Residential SOPs 6 

### ). Combined Risks Since the toxicological endpoint s for dermal and incidental oral exposure routes are based on toxicity studies that have a common effect (i.e., decreased body weight gain and food efficiency) , risk estimates have been combined for those routes. The incidental oral sc enarios (i.e., hand
- to mouth, object
- to - mouth , and soil ingestion) should be considered inter
- related and it is likely that

### Page 34 of 58

they occur interspersed amongst each other across time. Combining these scenarios with the dermal exposure scenario would be overl y- conservative because of the conservative nature of each individual assessment. Therefore, the post
- application exposure scenarios that were combined for children ( 1 to <2 years old) are the dermal and hand
- to - mouth scenarios. This combination should be considered a protective e stimate of children’s exp osure to pesticides used on turf
. Summary of Residential Post
- application Non
- Cancer Exposure and Risk Estimates All the short
- term MOEs for each scenario are greater than the LOC of 100 , and therefore, are not of concern
. **Table 6**  **.2. Residential Post**  **- application Non**  **- cancer Exposure and Risk Estimates for Pyraclostrobin.**  **Lifestage Post** **- application Exposure Scenario**  **Application Rate**  **1 Dose** 

**(m g/k** **g/day) 2**  **MOEs 3**  **Combined MOEs**  **4 Use Site**  **Route of Exposure** Adult To mato

Transplants Dermal 0.18 lb ai/A DFR = 0.379 μg/cm2 0.0013 3,800

NA Child (6
- 11 years old) 0.00077 6,500 Adult Gardens Dermal 0.12 lb ai/A DFR = 0.457 μg/cm2 0.017 290 Child (6
- 11 years old) 0.010 490 Adult Fruit and Nut

Trees Dermal 0.12 lb ai/A DFR = 0.457 μg/cm2 0.0016 3,200 Child (6
- 11 years old) 0.00093 5,400

Adult

Lawn/Turf Dermal High contact

0.5 lb ai/A

TTR = 0.035 μg/cm2 0.019 2 60 Dermal Mowing turf 0.000 39 13,0 00 Dermal Golfing 0.0015 3,3 00
Youth (11
- 16 years old) Dermal Mowing turf 0.000 39 13,0 00 Dermal Golfing 0.0015 3,3 00 Child (6
- 11 years old) Dermal Golfing 0.0018 2 ,800

Child (1< 2 years old) Dermal High contact 0.0 33 150 130 Incidental Oral Hand to mouth 0.0048 1,200 Incidental Oral Object to mouth 0.000 15 40 ,000 NA Incidental Oral Soil Ingestion 0.000017 34 0,000 NA 1 Based on the proposed garden/tree use on Bonide FT09 label (EPA Reg. No. 4
- UII); the proposed tomato transplant use on Pagent® Fungicide ( EP A Reg. No.7969
- 251); and the registered turf use on Insignia® Fungicide label (EPA Reg. No. 7969
- 184). 2 Dose (mg/kg/day) equations:

### Page 35 of 58

Dermal Dose (turf) Dermal Dose (gardens/trees) Dermal Dose (tomato transplants) Hand

- to -Mouth Dose = hand residue loading (mg/cm 2 ) × fraction of hand mouthed (0.127) × surface area of 1 hand (150 cm2 ) × exposure time (1.5 hrs/day) × # of replenishment intervals/hr (4 int/hr) × (1
- ((1
- saliva extraction factor (0.5))^(Number of hand
- to - mouth events per hour (13.9 events/hr) ÷ # of replenishment intervals/hr)) ÷ body weight (kg). Object

- to -Mouth Dose = object residue loading (μg/cm2 ) × unit conversion factor (0.001 mg/μg) × object surface area mouthed / event (10 cm2/event) × exposure time (1.5 hrs/day) × # replenishment intervals/hr (4 int/hr) × (1
- ( (1
- saliva extraction factor (0.50))^(# Object
- to - Mouth Events/hr (8.8 events/hr) ÷ # replenishment intervals/hr)) ÷ body weight (kg). Soil Ingestion = soil residue (μg/g) × ingestion rate (50 mg/day) × conversion factor (0.000001 g/μg) ÷ body weight (11 kg). TTR = 0.035 μg/cm2 (based on pyraclostrobin TTR study) 3 Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day). Incidental Oral MOE = Oral NOAEL (mg/kg/day) ÷ Incidental oral Dose (mg/kg/day). 4 Combined MOE = 1 ÷ (1/dermal MOE) + (1/incidental oral MOE), where applicable 

### 6.3 **Combined Residential Risk Estimates (Multiple Exposure Scenarios)** Because dermal post
- application exposure s to treated gardens , fruit or nut trees, tomato transplants, and turf could conceivabl y co - occur within the same day for adult s and children 6 to 11 year s old , combined exposures from these scenarios were co nsidered
. However, all four of these use sites/scenarios involved different labeled products, and therefore, the probability of co
occurrence is considered improbable. Therefore, assessments of these combined exposures were not conducted. **6.4 Residential Risk Estimates for Use in Aggregate Assessment**  Since the toxicity

effect from the inhalation route of exposure is different than the effect from the dermal route of exposure, inhalation and dermal exposures are not aggregated together. Therefore, separate inhalation and dermal aggregate assessments are evaluated. The scenarios with the highest exposures and corresponding lowest MOEs , provide d in Tables 6.1 and 6.2 , reflect the residential risk estimates that are recommended for use in the short
- term aggregate assessment for p yr aclostrobin. Table 6.4 summarizes the residential risk estimates that are recommended for use in the short
- term aggregate assessments for py raclostrobin.  The recommended residential inhalation exposure for use in the adult aggregate assessment reflects inhalation exposure from application of the WDG formulation to turf via manually

pressurized handwand or backpack sprayer.  The recommended residential dermal exposure for use in the adult aggregate assessment reflects dermal exposure from post
- application activities on treated turf.  The recommended residential dermal exposure for use in the child (11
- 16 yr) aggregate asse ssment reflects dermal exposure from post
- application golfing on treated turf.  The recommended residential dermal exposure for use in the child (6
- 11 y r) aggregate assessment reflects dermal exposure from post
- application activities in treated gardens.  The recommended residential exposure for use in the children (1<2 ye ars old) aggregate assessment reflects dermal and hand
- to - mouth exposures from post
- application exposure to treated turf.

### Page 36 of 58

**Table 6.4. Recommendations for the Residential Exposures for th e Pyraclostrobin Short** **- term Aggregate Assessments.**  **Lifestage Route of Exposure**  **Scenario Dose**  **(m g/k** **g/day) 4**  **MOE 5** 
Adult Inhalation Applying WDG formulation to turf via manually pressurized handwand or backpack sprayer 0.000 39 5 9 0 Dermal Post
- application activities on treated turf 0.019 260 Child (11
- 16 yr) Dermal Post
- application golfing on treated turf 0.0015 3,300 Child (6
- 11 yr) Dermal Post
- application activities in treated gardens 0.010 490 Child (1<2 years old) Combined

(incidental oral + dermal) Post
- application activities on treated turf 0.038 130 

### 6.5 **Residential Bystander Post**  **- application**  **Inhalation Exposure** Based on the Agency's current practices, a quantitative post
- application inhalation exposure assessment was not performed for p yr aclostrobin at this time primarily because of the low vapor pressure (1.9 x 10 - 8 

### mm Hg at 20 degrees) and the low proposed use rate (0.2 lb ai/A). However, 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 volatiliz ation 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 3 

### . The Agency is in the process of evaluating the SAP report and may , as appropriate, develop policies and procedures to identify the need for and, subsequently , the way to incorporate post
- application inhalation exposure into the Agency's risk assessments. If new policies or procedures are developed, the Agency may revisit the need for a quantitative post
application inhalation exposure assessment for p yraclostrobin. **6.6 Spray Drift**  Spray drift is always a potential source of exposure to residents nearby to spraying operations. This is particularly

the case with aerial app lication, but, to a lesser extent, could also be a potential source of exposure from the ground application method employed for py raclostrobin
. The Agency

has been working with the Spray Drift Task Force, EPA Regional Offices and State Lead Agencies for p esticide regulation and other parties to develop the best spray drift management practices (see the Agency ’s Spray Drift website for more information4 

### ). The Agency has completed its evaluation of the new database submitted by the Spray

Drift Task Force, a membership of U.S. pesticide registrants, and is developing a policy on how to appropriatel y apply

the data and the AgDRIFT computer model to its risk assessments for pesticides applied b y air, orchard airblast and ground hydraulic methods. After the pol icy is in place, the Agency

may impose further refinements in spray drift management practices to reduce off
- target drift with specific products with significant risk estimates associated with drift.

3 Available: http://www.ep a.gov/scipoly/SAP/meetings/2009/120109meeting.html 4 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm

### Page 37 of 58

It is noted that the 0.5 lb ai/acre application rate fo r turf was modeled to estimate post
application residential exposure of children. As this rate is equal to or higher than many of agricultural application rates, this scenario is protective of any exposure of farm children via spray drift from agricultural py raclostrobin applications. Although a quantitative residential post
- application inhalation exposure assessment was not performed as a result of pesticide drift from neighboring treated agricultural fields, an inhalation exposure assessment was perform ed for flaggers. This exposure scenario is representative of a worse case inhalation (drift) exposure and may be considered protective of most outdoor agricultural and commercial post
- application inhalation exposure scenarios
. **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 py raclostrobin , 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 py raclostrobin in food and drinking water, and does not include dermal, inhalation , or incidental oral exposure. The acute risk estimate for the U.S. population and all other population subgroups, resulting from aggregate exposure to py

raclostrobin in food and drinking water , is not of concern . The food and drinking water exposure estimates are 1.5 % of the aPAD for the U.S. general population, and 88 % for the most highly

exposed subgroup, females 13
- 49 years old. **7.2 Short** **- Term Aggregate Risk**  There is potential short
- term exposure to py rac lostrobin via dietary

(which is considered background exposure) and residential (which is considered primary) exposure pathways. For adults, these pathways lead to exposure via oral (background) as well as dermal and inhalation (primary) routes. The most conservative scenario s w ere ch osen for each population (e.g., hand
to - mouth exposure from treated turf for children 1
- 2 years old). For a description of the residential exposure scenarios considered in the aggregate assessment, see Section 6.4. The adult greatest exposure non - cancer aggregate MOE is 2 3 0 and is not of concern to HED. The aggregate MOE for children 1
- 2 years old, including incidental oral exposures from treated turf, is 1 2 0 and is not of concern to HED.

### Page 38 of 58

**Table 7.2.1**  **. Short** **- /Intermediate**  **- Term Aggregate Risk Calculations**  **Population Dermal Exposure**  **Oral Exposure Total**  **Combined MOE**  **2 NOAEL**  **mg/kg/day Exposure** 

**mg/kg/day MOE**  **1 NOAEL**  **mg/kg/day Incidental Oral** 

**Exposure mg/kg/day**  **Ch ronic Dietary** 

**(Food + Water) mg/kg/day**  **MOE 1**  Child 1
- 2 yrs 5 0.033 150 5.8 0.0048 0.009206 630 120 Child 6
- 11 yrs 5 0.01 490 5 NA 0.003525 1,400 360 Youth 11
- 16 yrs 5 0.0015 3,300 5 NA 0.001832 2,700 1,500 Adult Handler 5 0.004 1,300 5 NA 0.002707 1,800 760 Adult Post
- application 5 0.019 260 5 NA 0.002707 1,800 230 1 The Level of Concern MOE is 100. 2 Total Combined MOE = 1/ [(1/MOE Dermal ) + (1/MOE Oral )] 

### 7.3 **Intermediate -**  **Term Aggregate Risk** Based on the registered residential uses of p yraclostrobin on residential and golf course turf, intermediate
- term post application exposures are possible. However, since the short
- and intermediate
- term endpoints and PODs for dermal and oral routes are th e same, the short
- term exposure and risk estimates are considered to be protective of potential intermediate
- term exposure and risk. **7. 4**  **Chronic Aggregate Risk** Chronic exposure from the residential pathway is not anticipated based on the current py racl ostrobin 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 )
. The dietary exposure is estimated at 0.00 2944 mg/kg/day for the general U.S. population ( 8.7 % of the cPAD) and 0.00 9888 mg/kg/day ( 29 % of the cPAD) for children 1
- 2 years old, the population subgroup with the highest estimated chronic dietary exposure to p yr aclostrobin . See Section 5. 4.4 for details. **8.0 Cumulative Exposure/Risk**  **Characterization** Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to py ra clostrobin and any other substances and py raclostrobin does not appear to produce a toxic metabolite produced b y other substances. For the purposes of this tolerance action, therefore, EPA has not assumed that py ra clostrobin has a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by

EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

### Page 39 of 58

**9.0 Occupational Exposure/Risk Characterization**  Py raclostrobin is proposed for new occupational uses on sugarcane, globe artichoke, Belgium endive, persimmon, and greenhouse grown tomatoes. Application methods, maximum application rates, and use sites are summarized in Section 3.3 and Table 3.3. Based on the proposed use pattern s , there is a potential for short
- and intermediate
- term occupational exposure to py ra clostrobin during handling (mixing, loading, and appl ying) and post
- application activities. Py ra c lostrobin uses are propos ed for multiple app lications, with the retreatment intervals ranging from 7 to 28 days. The proposed labels require occupational handlers to wear the following personal protective equipment (PPE): long
- sleeved shirts, long pants, chemical resistant gloves, and coveralls in a few cases . The 12 hour restricted entry interval (REI) listed on the labels is appropriate. **9.1 Short** **- /Intermediate**  **- Term Handler Risk**  HED uses the term handlers to describe those individuals who are involved in the pesticide application process. HE D believes that there are distinct job functions or tasks related to applications 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 exposure levels to differ in a manner specific to each application event. Based on the anticipated use patterns from the proposed label s , ty pes of equipment and techniques that can potentially be used, occupational handler exposure is expected from the proposed uses. HED’s LOC for the MOE is defined by the uncertainty

factors that are applied to the assessment. HED applies a 10X factor to account for variability among species and a 10X factor to account for variability within species. The total uncertainty factor that has been applied to the non
- cancer assessment of py racl ostrobin is 100X for occupational exposure. Occupational exposure and risk resulting in MOEs greater than or equal to 100 will not be of concern to HED. Dermal and inhalation exposure estimates were not combined in this assessment, since the toxicological PODs are based on different toxicological effects. Summaries of the short
- and intermediate
- term non - cancer risk estimate s for occupational handlers appl ying py

ra clostrobin are provided in Appendix E , Tables E
- 1 and E
- 2
. The dermal MOEs range from 47 (mixing/loading of SC formulation to support aerial applications to sugarcane ) to 7 , 800 (applyingwith aerial equipment to ty pical acreage crops) at baseline PPE. The proposed labels require occupational handlers to wear the following personal protective equipment (PPE): long
- sleeved shirts, long pants, and chemical resi stant gloves. All of the dermal MOEs are greater than the LOC of 100 when assessed using labeled PPE (gloves) and are not a concern to HED. The inhalation MOEs range from 33 (mixing/loading of WDG formulation to support aerial and chemigation applicati ons to artichoke and persimmon) to 8 , 500 (applying with manually pressurized handwand equipment to greenhouse tomatoes) at baseline PPE (no respirator). The two inhalation scenarios with MOEs below 100 at baseline PPE [mixing/loading of WDG

### Page 40 of 58

formulation to support aerial and chemigation applications to artichoke and persimmon (MOE=33); and M/L/A of WDG formulation using a mechanically pressurized handgun to treat greenhouse tomatoes (MOE=85)] were no longer a concern to HED when assessed with a PF5 respirator (MOE s >100). A PF5 respirator needs to be proposed on the affected Pristine Fungicide [EPA Reg. No.7969
- 199] and Pagent® Fungicide [EPA Reg. No.7969
- 251] labels. **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, th e ty pe of pesticide application, and the chemical’s degradation properties. 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** Based on the proposed use patterns, short
- and intermediate
- term post - application dermal exposures to workers re
- entering treated areas is possible. Therefore, a post
- application risk assessment for dermal exposures is needed. It should be noted th at there is no post
- application dermal exposure anticipated for the proposed Belgium endive use, because the roots are treated with py raclostrobin prior to forcing in the trays. Thus there would be negligible exposure to the residue when the crop is harve sted or maintained. Dislodgeable Foliar Residues Chemical
- specific DFR data was previously submitted by the registrant to support earlier registration requests for food crops. An overview of each study was provided in a previous assessment (D269670, K. O’Rourke, 9/30/2002 ). 

### Py raclostrobin DFR studies were conducted on peaches, peanuts, strawberries, and grapes . PMRA performed the primary review of these data , and considered the results useful for risk assessment purposes. It should be noted that PMRA used the DF R data only

to calculate percent dissipation per day and half
- lives. Therefore, HED went back to the initial study to calculate the DFR on day zero based on the results of the DFR study. The calculated DFR values on day zero were used in the post - application dermal assessments. The PA peach DFR data, which resulted in the highest DFR values of the three study sites, were used in the persimmon assessment. The CA strawberry DFR data, which also resulted in the highest DFR values of the three s tudy

sites, were used in the artichoke and greenhouse tomato assessments. The TX peanut DFR data, which resulted in the highest DFR values of the three study sites, were used in the sugarcane assessment. The peanut DFR data were selected for use in the sugarcane assessment because the climate of regions where both of these crops are grown is very similar. The DFR data used in this assessment are presented in Appendix F, Tables F
- 1 through F
- 3. 

### Occupational Post
- application Non
- Cancer Dermal Risk Estimat es The short
- and intermediate
- term non - cancer post - application risk estimates for workers are provided in Appendix E, Table E
- 3. All post
- application scenarios resulted in MOEs greater

### Page 41 of 58

than 100 on day

0 (12 hours after application) , and therefore , are no t of concern to HED . The MOEs for p yraclostrobin ranged from 120 to 12,000. Restricted Entry

Interval The REI specified on the proposed label is based on the acute toxicity of py raclostrobin
. Py raclostrobin is classified as Toxicity Category III via the dermal route and for skin and eye 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 irrigation are assigned a 12
- hour REI
. Furtherm ore, the s hort
- and intermediate
- term post - application risk estimates were not a concern on day

0 (12 hours following application) for all post
- application activities. Therefore, the [156 subpart K] Worker Protection Statement interim REIof 12 hours is adequate to protect agricultural workers from post
- application exposures to py raclostrobin. **9.2.2 Inhalation Post** **- Application**  **Risk** Based on the Agency's current practices, a quantitative post
- application inhalation exposure assessment was not performed for p yr aclostrobin at this time primarily because of the low vapor pressure ( 1.9 x 10 - 8 

### mm Hg at 20 degrees C) and the low proposed use rate (0.2 lb ai/A). However, there are multiple potential sources of post
- application inhalation exposure to individual s 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 5 

### . The Agency is in the process of evaluating the SAP report as well as available post
- application inhalation exposure data generated by the ARTF and may , as appropriate, develop policies and procedures, to identify

the need for and, subsequently , the way to incorporate occupational post
application inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post - application inhalation exposure assessment for py raclostrobin. Although a quantitative 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. The Worker Protection Standard for Agricultural Pesticides contains requirements for protecting workers from inhalation exposures during and after greenhouse applications through the use of ventilation requirements [40 CFR 170.110, (3) (Restrictions associated with pesticide applications)].

5 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html

### Page 42 of 58

**1 0.0**  **References** S. Funk, 4/ 30 /13 , DP403449. Py raclostrobin: Request for the Use on Sugarcane
. Summary of Analy tical Chemistry

and Residue Data. S. Funk, 4/ 30 /13 , DP 398877
. Boscalid and P yr aclostrobin: Application by Bonide Products, In c. to Register an End Use Product Containing P yraclostrobin, Boscalid, and Lambda Cy halothrin for Homeowner Use on Pome Fruit, Stone Fruit, and Tree Nuts. S. Funk, 4/ 30 /13 , DP 406471
. Py raclostrobin and Boscalid: Request to Add Indoor Use on Greenhouse Tomato for Commercial Production and on Greenhouse/Lathhouse Transplants for Consumer Home Market. PagentTM Fungicide Reg. No. 7969
- 251. S. Funk, 6 /24/13 , DP 4 10737
. Amended: Py raclostrobin: Petition for the Establishment of Permanent Tolerances and Registration for Use on Belgium Endive, Persimmon, and Globe Artichoke. Request for Crop Group Expansions/Revisions for Bulb Vegetable Group 3
- 07, Fruiting Vegetable 8
- 10, Citrus Fruit Group 10
- 10 , Pome Fruit Group 11
- 10, Berry Subgroups 13
- 07A, B, F, and G, and Oilseed Group 20. Summary of Anal ytical Chemistry

and Residue Data S. Funk, 4/30/13 , DP 410739. Py raclostrobin
. Acute and Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessments to Support New Uses on Sugarcane, Persimmon, Globe Artichoke, and Belgium Endive. C. Walls, 4/ 30 / 13 , DP 403449
. Py raclostrobin. Occupational and Residential Exposure Assessment for proposed new uses of p yr aclostrobin on sugarcane, globe artichoke, Belgium endive, persimmon, greenhouse grown tomato transplants grown for home consumer market, and residential ornamentals, landscape gardens, fruit trees and nut trees
. F. Khan, 4/4/13, DP403871. Addendum of Drinking Water Exposure Assessment for the Section 3 New Uses of Pyraclostrobin on Various Agricultural Crops and Residential Ornamentals. S. Haddad, 11/18/2012, SIAB/BEAD, Screening Level Estimates of Agricultural Uses (SLUA) for the Fungicide Py

raclostrobin (099100)

### Page 43 of 58

**A ppendix**  **A .**  **Toxi cology Profile and Executive Summaries**  **A.1 Toxicology Data Requirements**  The requirements (40 CFR 158.500) for food uses are in the table below. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used. **Table A.1: Toxicology Studies**  **Required Subm** **itted Satisfied**  870.1100 Acute Oral Toxicity
................................ ................................ ................................ 870.1200 Acute Dermal Toxicity
................................ ................................ ............................... 870.1300 Acute Inhalation Toxicity
................................ ................................ .......................... 870.2400 Acute Eye Irritation
................................ ................................ ................................ 870.2500 Acute Dermal Irritation
................................ ................................ .............................. 870.2600 Skin Sensitization
................................ ................................ ................................ yes yes yes yes yes yes yes

yes yes yes yes yes yes

yes yes yes yes yes 870.3100 90
- Day Oral Toxicity in Rodents
................................ ................................ 870.3150 90
- Day Oral Toxicity in Non
- Rodents
................................ ................................ 870.3200 21/28
- Day Dermal Toxicity
................................ ................................ ....................... 870.3250 90
- Day Dermal Toxicity
................................ ................................ ............................ 870.3465 90
- Day Inhalation Toxicity
................................ ................................ ........................ yes yes yes no (CR) yes (CR) yes

yes yes no yes yes

yes yes

--- yes 870.3700 Prenatal Developmental Toxicity Study (Rodent)
................................ ...................... 870.3700 Prenatal Developmental Toxicity Study (Non
- Rodent)
................................ 870.3800 Reproduction and Fertility Effects
................................ ................................ yes yes yes yes

yes yes yes

yes yes 870.4100 Chronic Toxicity (Rodent)
................................ ................................ ......................... 870.4100 Chronic Toxicity (Non
- Rodent)
................................ ................................ ................. 870.4200 Carcinogenicity ( Two Rodent Species; Rat and Mouse )
................................ 870.4300 Combined Chronic Toxicity/Carcinogenicity
................................ ............................ yes no yes no yes

yes yes no yes

--- yes yes 870.5100 Bacterial Reverse Mutation Test
................................ ................................ ................ 870.5300 in vitro Mammalian Cell Gene Mutation Test
................................ ............................ 870.5375 in vitro Mammalian Chromosome Aberration Test
................................ .................... 870.5385 Mammalian Bone Marrow Chromosomal Aberration Test
................................ 870.5395 Mammalian Erythrocyte Micronucleus T est ................................ .............................. 870.5550 Unscheduled DNA Synthesis in Mammalian Cells in Culture
................................ yes yes yes

--- yes no yes

yes yes no yes yes yes

yes yes

--- yes

- -- 870.6100 Delayed Neurotoxicity of Organophosphorus Substances (Acute, Hen)
.................... 870.6100 Delayed Neurotoxicity of Organophosphorus Substances (28
- Day, Hen)
................. 870.6200 Neurotoxicity Screening Battery (Acute, Rat)
................................ ........................... 870.6200 Neurotoxicity Screening Battery (Subchronic, Rat)
................................ ................... 870.6300 Developmental Neurotoxicity Study
................................ ................................ no (CR) no (CR) yes yes no (CR) no

no yes yes no - --

- -- yes yes

- -- 870.7200 Companion Animal Safety
................................ ................................ ......................... 870.7485 Metabolism and Pharmacokinetics
................................ ................................ 870.7600 Dermal Penetration
................................ ................................ ................................

in vitro Dermal Penetration
................................ ................................ ........................ 870.7800 Immunotoxicity
................................ ................................ ................................ no (CR) yes no (CR) no yes no

yes yes no yes -- -

yes

---

---

--- CR : Conditionally Required 

### A.2 **Toxicity Profile s**  **Table A.2.1. Acute Toxicity of Pyra clostrobin**  **Table A.2.1: Acute Toxicity**  **Profile Guideline**  **Study Type MRID**  **Results Toxicity**  **Category** 870.1100 Acute Oral Toxicity 45118302 LD 50 ≥ 5000 mg/kg IV 870.1200 Acute Dermal Toxicity 45118305 LD 50 >2000 mg/kg III 870.1300 Acute Inhalation Toxicity 45118308 0.31 mg/L < LC 50 < 1.07 mg/L II 870.2400 Acute Eye Irritation 45118311 Minimal Eye Irritation Maximum Average Score (MAS): 4.6 / 110 24 hr Maximum Irritation Score (MIS): 6.3 / 110 III

### Page 44 of 58

**Table A.2.1: Acute Toxicity**  **Profile Guideline**  **Study Type MRID**  **Results Toxicity**  **Category** 870.2500 Acute Dermal Irritation 45118314 Moderate Skin Irritation Maximum Average Score (MAS): 2.2 / 8.0 24 h Maximum Irritation Score (MIS): 2.7 / 8.0 III 870.2600 Dermal Sensitization 45118317 Not a dermal sensitizer N/A 

### Table A.2.2. Non **- acute Toxicity Profile for Pyra**  **clostrobin Table A.2.**  **2 .**  **Subchronic, Chronic, and Other Toxicity Profiles Guideline**  **Study Type MRID (year) / Doses / Classification**  **Results** 870.3050 Repeated Dose

28
- Day Oral Toxicity in Rodents (Rat) 45118322 (1999)

Dietary Concentration (ppm): 0, 20 , 100 , 5 0 0 , 150 0 Intake Dose (mg/kg/day) : M: 0, 1.8 , 9.0 , 42.3, 120.2 F : 0, 2.0 , 9.6 , 46.6, 126.3 Acceptable / Guideline NOAEL (mg/kg/day) : M = 9.0 F = 9.6 LOAEL (mg/kg/day) : M = 42.3 F = 46.6 Based on changes in hematology parameters, increased spleen weight (both absolute and relative) , and histopathology in the spleen and liver, in addition to increased duoden al mucosal hyperplasia
. 870.3100 90
- Day Oral Toxicity

in Rodents (Rat) 45118321 ( 1999 )

45118322 (1999)

– Dose Selection Dietary Concentration (ppm): 0, 50 , 150 , 5 0 0 , 100 0 1500 Intake Dose (mg/kg/day) : M: 0, 3
. 5 , 10.7 , 34.7, 68.8, 105.8 F: 0, 4.2 , 12.6 , 40.8, 79.7, 118.9 Acceptable / Guideline NOAEL (mg/kg/day): M = 10.7 F = 12.6 LOAEL (mg/kg/day): M = 34.7 F = 40.8 B ased on decreased body weights/body weight gains (males), decreased food consumption, increased relative liver weight and absolute and relative spleen weight in females, and histopathology of the duodenum, spleen and liver. 90
- Day Oral Toxicity in Rodents (Mouse ) 45118320 (199 9 )

Dietary Concentration (ppm): 0, 50 , 150 , 5 0 0 , 100 0 1500 Intake Dose (mg/kg/day) : M: 0, 9.2 , 30.4 , 119.4, 274.4, 475.5 F: 0, 12.9 , 40.4 , 162.0, 374.1, 634.8 Acceptable / Guideline NOAEL (mg/kg/day) : M = 9.2 F = 12
. 9 LOAEL (mg/kg/day) : M = 30.4 F = 4 0 .4 Based on decreased body weights/body weight gains (males), changes in clinical chemistry (increased urea and decreased triglycerides), and increased incidences in females of lymph node apoptosis, thymus atropy, and ulcer/erosion in the glandular stomach. 870.3150 90
- Day Oral Toxicity

in Non
- Rodents (Dog) 45118323 ( 1999 )

Dietary Concentration (ppm): 0, 100 , 200 , 4 50 Intake Dose (mg/kg/day) : M: 0, 2.8 , 5.8 , 12.9 F: 0, 3.0 , 6.2 , 13.6 Acceptable / Guideline NOAEL (mg/kg/day) : M = 5.8 F = 6.2 LOAEL (mg/kg/day) : M = 12.9 F = 13.6 Based on an increased incidence of diarrhea, clinical chemistry changes and mucosal hypertrophy of the duodenum (both sexes) and body weight loss, decreas ed food intake and decreased food efficiency (females only). 870.3200 21/28
- Day

Dermal Toxicity (Ra bbi t) 4 5118324 ( 1999 )

Applied Dose (mg/kg/day) : M: 0 , 40 , 100 , 250 F: 0 , 40 , 100 , 250 Unacceptable / G

uideline Unacceptable due to the lack of systemic effects at the highest dose tested (250 mg/kg/day); the limit dose is 1000 mg/kg/day. Dermal NOAEL (mg/kg/day) : M = 40 F = 40 LOAEL (mg/kg/day) : M = 100 F = 100 Based on scale formation, hyperkeratosis, and epidermal thickening at the site of application. Systemic NOAEL (mg/kg/day) : M = 250 F = 250 LOAEL (mg/kg/day) : M > 250 F > 250

### Page 45 of 58

**Table A.2. 2**  **. Subchronic, Chronic, and Other Toxicity Profiles**  **Guideline Study Type**  **MRID (year) / Doses / Classification Results**  870.3465 28
- Day

Inhalation Toxicity (Rat) 46638801 (2005)

Applied Dose (mg/L) : M: 0 , 0.001 , 0.030 , 0.300 F: 0 , 0.001 , 0.030 , 0.300 Acceptable / G

uideline NOAEL (mg/L) : M = 0.001 F = 0.001 LOAEL (mg/L) : M = 0.030 F = 0.0 3 0 Based on findings of hyperplasia in the duodenum, alveolar histiocytosis in the lungs, and olfactory atrophy/necrosis in the nasal tissues. 870.3700 Prenatal

Developmental Toxicity Study (Rat) 45118325 (19 99 ) Gavage Dose (mg/kg/day) : F: 0 , 10 , 25 , 50 Acceptable / Guideline Maternal NOAEL (mg/kg/day) = 10 LOAEL (mg/kg/day) = 25 Based on decreased body weights and body weight gains and reduced food consumption and reduced food efficiency. Developmental NOAEL (mg/kg/day) = 25 LOAEL (mg/kg/day) = 50 Based on increased incidence of dilated renal pelvis and cervical ribs. Prenatal Developmental Toxicity Study (Rabbit) 45118326 (1999)

45437001 (2001) Gavage Dose (mg/kg/day): F: 0 , 1 , 3 , 5, 10, 20 Acceptable / Guideline Maternal NOAEL (mg/kg/day) = 5 LOAEL (mg/kg/day) = 10 Based on body weight gains, reduced food consumption and reduced food efficiency. Developmental NOAEL (mg/kg/day) = 5 LOAEL (mg/kg/day) = 10 Based on increased resorptions per litter, increased post
implantation loss and dams with total resorptions. 870.3800 Reproduction and

Fertility Effects (Rat) 45118327 ( 1999 )

Dietary Concentration (ppm): 0, 25 , 75 , 30 0 Intake Dose (mg/kg/day) : M 0 : 0, 2.5 , 7.4 , 29.0 F 0 : 0, 2.6 , 7.8 , 30.4 M 1 : 0, 2.8 , 8.6 , 35.0 F 1 : 0, 3.0 , 9.0 , 36.0 Acceptable / Guideline Parental NOAEL (mg/kg/day) : M = 29.0 F = 30.4 LOAEL (mg/kg/day) : M > 29.0 F > 30.4 Reproductive NOAEL (mg/kg/day) : M = 29.0 F = 30.4 LOAEL (mg/kg/day) : M > 29.0 F > 30.4 Offspring NOAEL (mg/kg/day) : M = 29.0 F = 30.4 LOAEL (mg/kg/day) : M > 29.0 F > 30.4 45596210 (2002 ) Dietary Concentration (ppm): 0, 200 , 400 , 60 0 Intake Dose (mg/kg/day) : M: 0, 20.5 , 39.9 , 59.1 F: 0, 21.3 , 42.5 , 60.4 Acceptable / Non
- Guideline One
- Generation Study Parental NOAEL (mg/kg/day) : M = 20.5 F = 42.5 LOAEL (mg/kg/day) : M = 39.9 F = 60.4 B ased on reduced body weights and body weight gains
. Reproductive NOAEL (mg/kg/day) : M < 20.5 F < 21.3 LOAEL (mg/kg/day) : M ≤ 20.5 F ≤ 21.3 Offspring NOAEL (mg/kg/day) : M ≥ 59.1 F ≥ 60.4 LOAEL (mg/kg/day) : M > 59.1 F > 60.4 Based on a reduced pup body weights and body weight gains (a threshold body weight effect).

### Page 46 of 58

**Table A.2. 2**  **. Subchronic, Chronic, and Other Toxicity Profiles**  **Guideline Study Type**  **MRID (year) / Doses / Classification Results**  870.4100 Chronic T oxicity

( Rat) 45118329 (199 9 )

Dietary Concentration (ppm): 0, 25 , 75 , 2 0 0 Intake Dose (mg/kg/day) : M: 0, 1.1 , 3.4 , 9.0 F: 0, 1.5 , 4.6 , 12.3 Unacceptable / Guideline Unacceptable due to low dose selection NOAEL (mg/kg/day) : M = 9.0 F = 1 2 .3 LOAEL (mg/kg/day) : M > 9 .0 F > 12. 3 There was no evidence of carcinogenic potential

Chronic T oxicity (Dog) 45118328 (199 9 )

Dietary Concentration (ppm): 0, 100 , 200 , 4 0 0 Intake Dose (mg/kg/day) : M: 0, 2.7 , 5.4 , 10.8 F: 0, 2.7 , 5.4 , 11.2 Acceptable / Guideline NOAEL (mg/kg/day) : M = 5.4 F = 5.4 LOAEL (mg/kg/day) : M = 10.8 F = 11.2 Based on an increased incidence of diarrhea and clinical chemistry changes (both sexes) and decreased body weight gain, decreased food intake and decreased food efficiency (females only). 870.4200 Carcinogenicity (Rat) 45118331 (199 9 ) Dietary Concentration (ppm): 0, 25 , 75 , 2 0 0 Intake Dose (mg/kg/day) : M: 0, 1.2 , 3.4 , 9.2 F: 0, 1.5 , 4.7 , 12.6 Acceptable / Guideline NOAEL (mg/kg/day) : M = 3.4 F = 4.7 LOAEL (mg/kg/day) : M = 9.2 F = 12.6 Based on differences in body weight and body weight gains, increased incidences of kidney tubular casts and atrophy in males and females, and in males, an increased incidence of necrosis of the liver, gross and microscopic evidence of erosion/ulcer of the glandular stomach and an increased incidence of acanthosis and ulcers of the forestomach. Under the conditions of th is study, there wa s no evidence of carcinogenic potential
. Carcinogenicity ( Mouse ) 45118330 (199 9 )

Dietary Concentration (ppm): M: 0, 10 , 30 , 120 F: 0, 10 , 30 , 120 , 180 Intake Dose (mg/kg/day) : M: 0, 1.4 , 4.1 , 17.2 F: 0, 1.6 , 4.8 , 20.5 , 32.8 Unacceptable / Guideline Unacceptable due to low dose selection NOAEL (mg/kg/day) : M ≥ 17.2 F ≥ 32.8 LOAEL (mg/kg/day) : M > 17.2 F > 32.8 Under the conditions of this study, there was no evidence of carcinogenic potential
.

870.5100 Bacterial Reverse

Mutation Test ( Salmonella typhimurium) 45118332 (1997)

Applied Dose ( μg/

plate ) :  S9: 0 , 20 , 100 , 500 , 2500 , 5000 Acceptable / G

uideline ±S9: Negative up to 2500 μg/plate in the absence of cy totoxicity with precipitation above this concentration. There was no evidence of treatment
- induced mutant colonies above background levels. 870.5300 in vitro Mammalian

Cell Gene Mutation Test (Mouse Lymphoma Cells) 45118335 (1998)

Applied Dose ( μg/mL) :  S9: 0.625 , 1.25 , 2.5 , 5.0 , 10.0 , 20.0

 S9: 3 , 4 , 5 , 6 , 7 , 8  S9: 1.25 , 2.5 , 5.0 , 10.0 , 20.0 Acceptable / G

uideline BAS 500 F was tested up to cytotoxic and solubility limit concentrations. The positive controls induced the appropriate response. There was no evidence of induced mutant colonies over background.

### Page 47 of 58

**Table A.2. 2**  **. Subchronic, Chronic, and Other Toxicity Profiles**  **Guideline Study Type**  **MRID (year) / Doses / Classification Results**  870.5375 in vitro Mammalian

Chromosome Aberration Test ( C hinese H amster O vary cells ) 45118333 (1999)

Applied Dose ( μg/mL) :  S9: 0 , 6.25 , 12.5 , 25.0 +S9: 0 , 3.125 , 6.25 , 12.5

 S9: 0 , 0.005 , 0.010 , 0.050 , 0.100 Acceptable / G

uideline BAS 500 F was tested up to preciptating concentrations. Positive controls induced the appropriate response. There was no evidence of an increase in the number of structural or numerical chromosomal aberrations induced over background. It is therefore concluded that BAS 500 F is not a clastogeni c agent under the conditions of this study. 870.5395 Mammalian

Erythrocyte Micronucleus Test (Mouse) 45118334 (1 998 )

Gavage Dose (mg/kg/day): M : 0 , 75 , 150 , 300 F : 0 , 75 , 150 , 300 Acceptable / Guideline There was no significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow at any dose level tested, at any time af ter treatment. It is therefore concluded that BAS 500 F did not induce a clastogenic effect in either sex at any sacrifice time. 870.55 5 0 Unscheduled DNA

Synthesis in Mammalian Cells in Culture (Rat Hepatocytes) 45118336 (1998)

Applied Dose ( μg/mL) : Run 1: 0.01 , 0.03 , 0.1, 0.3, 1.0 Run 2: 0.004 , 0.02 , 0.5 Acceptable / G

uideline BAS 500 F was tested up to cytotoxic concentrations. The positive controls induced the appropriate response. There was no evidence that BAS 500 F induced unscheduled DNA sy

nthesis, as determined by net nuclear silver grain counts. 870.6 2 00 Acute N eurotoxicity

Screening Battery (Rat) 45118337 (1 999 )

Gavage Dose (mg/kg/day): M : 0 , 100 , 300 , 1000 F : 0 , 100 , 300 , 1000 Acceptable / Guideline Neurotoxicity NOAEL (mg/kg/day): M = 1000 F = 1000 LOAEL (mg/kg/day): M > 1000 F > 1000 Systemic NOAEL (mg/kg/day): M = 300 F = 1000 LOAEL (mg/kg/day): M = 1000 F > 1000 For males, based on 33% decreased body weight gain (p  0.01) on days 0
- 7; no similar effect was detected on days 0
- 14. 90
- Day Neurotoxicity Screening Battery (Rat) 45118 401 (1999)

Dietary Concentration (ppm): 0, 50 , 250 , M: 750

F: 1500 Intake Dose (mg/kg/day): M: 0, 3.5 , 16.9 , 49.9 F: 0, 4.0 , 20.4 , 111.9 Acceptable / Guideline Neurotoxicity NOAEL (mg/kg/day): M = 49.9 F = 111.9 LOAEL (mg/kg/day): M > 49.9 F > 111.9 Systemic NOAEL (mg/kg/day): M = 16.9 F = 20.4 LOAEL (mg/kg/day): M = 49.9 F = 111.9 Based on decreased body weight gain, food intake and food efficiency (both sexes) and decreased water intake (males only).

### Page 48 of 58

**Table A.2. 2**  **. Subchronic, Chronic, and Other Toxicity Profiles**  **Guideline Study Type**  **MRID (year) / Doses / Classification Results**  870.7485 Metabolism and

Pharmacokinetics (Rat) 45118403 (19 98 )

45118404 (1999) Gavage Dose (mg/kg): Single: 5, 50 Repeated: 50 Acceptable / G

uideline Nearly 35% of an oral dose of pyraclostrobin is absorbed with urinary and fecal excretions accounting for about 15% and 85%, respectively, and bile elimination accounted for about 30%. Two peak plasma concentrations were reached at 0.5
- 1 and 8 hours with lower plasma concentrations in males than females (by 16
- 38%) during the early peak phase. Elimination was biphasic at a low dose with plasma half lives of nearly 10/35 hours and monophasic at a high dose with a half
life of nearly 20 hours. Tissue distribution was fast, peaking at 0.5 hours, and was slightly higher among females. Some of the highest concentrations were found in the liver, thyroid, kidney, lung, adrenal glands, and pancreas but all levels dropped by more than 20
- fold within 72 hours. About 33 metabolites were identified in urine, feces, and bile with no sex
- or dose
- related differences but the position of the label seemed to alter the profile, particularly in the urine. Desmethoxy pyraclostrobin (500M07) is one of the major metabolites in rat and is also found in large amounts in plants (BF 500
- 3) and livestock (500M07). The rat metabolic pathway included phase
- I reactions such as N
- demethoxylation, various hydroxylations, and cleavage of the ether bond with subsequent oxidation; these reactions were follo wed by phase II glucuronidation and sulf ation.

### Page 49 of 58

**Table A.2. 2**  **. Subchronic, Chronic, and Other Toxicity Profiles**  **Guideline Study Type**  **MRID (year) / Doses / Classification Results**  870.7600 Dermal Penetration

(Rat) 4 5118402 ( 1999 )

Applied Dose (mg/cm2 ) : M: 0.015 , 0.075 , 0.375 Unacceptable / G

uideline Unacceptable because the actual dose was indeterminate due to material retained on the dressings being unavailable for absorption. The HIARC calculated and recommended a dermal penetration rate of 14%. (TXR#0051553: 10 FEB 2003) In all three doses the largest portion of the dose was found in the Dressings (72.38
- 84.36%, 78.51
- 81.58% and 76.38
- 80.24% for the respective doses) The dressings consisted of silicone ring, nylon mesh cover and porous band age. This material must be considered unavailable for ab sorption. Dermal penetration of [ 14 C
- tolyl]
-pyraclostrobin was low for all dose groups and time intervals (0.44
- 2.60%). After an 8
- hour exposure period, absorbed radioactivity accounted for 0.65%, 0.86% and 0.50% of the applied dose at nominal doses of 0 .015, 0.075 and 0.375 mg/cm2 , respectively. After removal of the test substance and washing the site, absorption continued
- an additional 0.93
- 1.74% of the dose in each dose group over the next 64 hours; however, there was no concomitant decrease in radio activity in the skin. The percent of the dose absorbed was not dose dependent; however, the actual amount of the test material absorbed did increase with increasing dose level. Immediately following the 8
- hour exposure period, absorbed radioactivity accounted f or 0.105, 0.757 and 2.27 μg/cm2 at mean achieved doses of 0.017, 0.087 and 0.428 mg/cm2

. Com paring the increases from the low to high
- dose groups, the amount of actual absorption increased by 21.6x compared to the 25.2x increase in the dose level. Th is pattern of absorption is commonly seen with a chemical which directly damages the stratum corneum of the skin. 870.7800 Immunotoxicity

(Mouse) 4 8830601 (1999)

Dietary Concentration (ppm): 0, 50 , 20 0 , 750 Intake Dose (mg/kg/day): F: 0, 13 , 50 , 1 65 Unclassified Preliminary review of the studies does not indicate any immunotoxicity or systemic toxicity below 165 mg/kg/day.
48830602 (2012) Dietary Concentration (ppm): 0, 50 , 20 0 , 750 Intake Dose (mg/kg/day): F: 0, 13 , 50 , 202 Unclassified 48830603 (2012) Dietary Concentration (ppm): 0, 50 , 20 0 , 750 Intake Dose (mg/kg/day): F: 0, 14 , 55 , 1 91 Unclassified

### Page 50 of 58

**Appendix B. Physicochemical Properties of Pyra**  **clostrobin .**  **TABLE B. Physicochemical Properties of Technical Grade Pyraclostrobin.**  Parameter Value References 1 (MRID) Melting point/range 63.7
- 65.2oC 45118213 pH Not applicable Density 1.367 g/cm3 4511821 4 Water solubility at 20 oC 1.9 ± 0.17 mg/L (deionized water, pH 5.8) 451182 3 3 Solvent solubility n - heptane (0.37 g/100mL); 2
- propanol (3.0 g/100mL); 1
- octanol (2.42 g/100mL); olive oil (2.80 g/100m/L); methanol (10.08 g/100mL); >50 g/100mL in acetone, ethyl acetate , acetonitrile, dichloromethane and toluene. 451182 28

Vapor pressure 2.6 x 10 - 10 hPa at 20 oC 4511821 4 Dissociation constant, pKa None (no dissociable moieties) Octanol/water partition coefficient, Log(KOW) at room temperature 3.990 mean log Pow; Pow is 9772 4511821 5 UV/visible absorption spectrum The structural identity of BAS 500 F was confirmed by NMR and MS spectra. UV molecular extinction (e [1 mol - 1 cm- 1 ]): 2.5x10 4 at 205 nm; 2.4x10 4 at 275 nm. 1996/10955 2

1 Product Chemistry data were reviewed by the Registration Division (D P# 269848 and D P# 274191, 5/3/01, 5/15/01, and 6/7/01, S. Malak)
. 2 BASF Document Number. 

### 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 C hemicals 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 51 of 58

**Appendix D. Summaries of Field Residue Data TABLE**  **D -**  **1 .**  **Summary of Residue Data from Crop Field Trials with Pyraclostrobin**  **on Sugarcane .**  Commodity Total

Applic. Rate (lb ai/A) [ kg ai/ha] PHI

(days) Analyte Residue Levels 1 (ppm) n Sample Min. Sample

Max. LAFT 2 HAFT 2 Median Mean Std. Dev.
Sugarcane 0.78
- 0.81

(0.88
- 0.91) 13
- 14 Py raclostrobin 8 <0.02 0.1049 <0.02 0.099 0.058 <0.060 0.026 BF 500
- 3 8 <0.02 0.0267 < 0.02 0.027 <0.02 <0.021 0.002 Combined 8 <0.04 <0.125 <0.040 <0.119 <0.076 <0.076 0.029 27
- 28 Py

raclostrobin 8 <0.02 0.0866 <0.020 0.068 0.043 <0.044 0.016 BF 500
- 3 8 <0.02 <0.02 <0.02 <0.02 <0.02 <0.02 N/A Combined 8 <0.04 <0.1066 <0.04 0 < 0.088 <0.062 <0.061 0.017 Sugarcane (for processing) 3.94
- 3.99

[4.42
- 4.47] 14 Py raclostrobin 2 0.0238 0.2935 0.028 0.255 0.141 0.141 N/A BF 500
- 3 2 <0.02 0.0253 <0.02 0.025 <0.022 <0.022 N/A Combined 2 <0.044 0.319 <0.048 0.280 <0.164 <0.164 N/A 28 Py raclostrobin 2 0.0203 0.3811 3 0.026 0.268 0.147 0.147 N/A BF 500
- 3 2 <0.02 0.0405 <0.02 <0.030 <0.025 <0.025 N/A Combined 2 <0.040 0.422 <0.046 <0.299 <0.172 <0.172 N/A
**TABLE D**  **- 2. S**  **ummary of Residue Data from Globe Artichoke**  **Crop Field Trials with Pyraclostrobin.**  Commodity Total Applic.

Rate (lb ai/A) [kg ai/ha] PHI

(days) Analyte Residue Levels 1 (ppm) n Sample Min. Sample

Max. LAFT 2 HAFT 2 Median Mean Std. Dev. Artichoke Flower Head 0.549
- 0.562

(0.615
- 0.630) 0 Py raclostrobin 3 0.514 1.110 0.618 1.045 0.759 0.807 0.218 BF 500
- 3 3 <0.02 0.0 56 <0.02 0.056 <0.02 8 <0.0 35 0.0 19 Combined 3 <0. 534 1.166 <0. 638 1.101 <0. 787 <0. 842 0. 236 1 Except for sample min/max, values reflect per trial averages; n = no. of field trials. For calculation of median, mean, and standard deviation, the LLMV (0.02 ppm) was used for any results reported as <LLMV in Table C.3. 2 LAF T = lowest average field trial; HAFT = highest average field trial.

### Page 52 of 58

**TABLE D**  **- 3.**  **Summary o f Residue Data from**  **Belgium Endive Crop Field Trials with Pyraclostrobin.**  Commodity Rate 1 PHI (days) Analyte Residue Levels 2 (ppm) n Sample Min. Sample

Max. LAFT 3 HAFT 3 Median Mean Std. Dev. **Treat me**  **nt 02: One pre -**  **cold -**  **storage application to**  **roots** Belgium endive heads 0.578
- 0.597 g

ai/100 lb of roots 25
- 27 Py

raclostro bin 3 <0.02 0.0679 <0.023 0.059 <0.040 <0.041 0.018 BF 500
- 3 3 <0.02 <0.02 <0.02 <0.02 <0.02 <0.02 N/A Combined 3 <0.04 <0.088 <0.043 <0.079 <0.06 <0.061 0.018 **Treat me**  **nt 03: One pre -**  **forcing application to**  **roots in packing tray** Belgium endive heads 0.089
- 0.097 g

ai/ft2 17
- 19 Py

raclostrobin 3 0.1239 1.7620 0.150 1.347 0.900 0.799 0.605 BF 500
- 3 3 <0.02 <0.02 <0.02 <0.02 <0.02 <0.02 N/A Combined 3 <0.144 <1.782 <0.170 <1.367 <0.920 0.819 0.605 **Treat me**  **nt 04: One pre -**  **cold -**  **storage application to**  **roots + One pre -**  **forcing application to**  **roots in packing tray** Belgium endive heads 0.584
- 0.591 g

ai/100 lb of roots **and** 3 0.092
- 0.101 g ai/ft2 17
- 19 Py

raclostrobin 3 0.2250 0.8710 0.256 0.771 0.551 0.526 0.258 BF 500
- 3 3 <0.02 <0.02 <0.02 <0.02 <0.02 <0.02 N/A Combined 3 <0.245 <0.891 <0.276 <0.791 <0.571 <0.546 0.258 1 Rate for pyraclostrobin , as calculated by the study reviewer based on the certificate of analysis of applied product in the study report. 2 Except for sample min/max, values reflect per trial averages; n = no. of field trials. For calculation of median, mean, and standard deviation, the LLMV (0.02 ppm) was used for any results reported as <LLMV in Table C.3. N/A = Not Applicable. 3 LAF T = lowest average field trial; HAFT = highest average field trial.
**TABLE D**  **- 4**  **. Summary of Residue Data from**  **Persimmon Crop Field Trials with Pyraclostrobin.**  Commodity Total Applic.

Rate (lb ai/A) [kg ai/ha] PHI

(days) Analyte Residue Levels 1 (ppm) n Sample Min. Sample

Max. LAFT 2 HAFT 2 Median Mean Std. Dev. Persimmon Fruit 0.564
- 0.573

(0.6 32
- 0.6 42 ) 0 Py raclostrobin 3 0.421 1.278 0.092 1.155 0.437 0.561 0.542 BF 500
- 3 3 <0.02 0.077 <0.02 0.073 <0.02 <0.038 0.031 Combined 3 <0.103 1.355 <0.112 1.228 <0.457 <0.599 0.571 1 Except for sample min/max, values reflect per trial averages; n = no. of field trials. For calculation of median, mean, and standard deviation, the LLMV (0.02 ppm) was used for any results reported as <LLMV in Table C.3. N/A = Not Applicable. 2 LAF T = lowest average field trial; HAFT = highest average field trial.

### Page 53 of 58

**Appendix E. Summaries of Occupational Handler and Post -**  **application Exposure and Risk Estimates Table**  **E -**  **1. Occupational Handler Non**  **- Cancer Exposure a**  **nd Risk Estimates for Pyr aclostrobin**  **. Exposure Scenario**  **Crop Dermal Unit**  **Exposure ( μ**  **g/lb ai) 1**  **Inhalation Unit**

**Exposure ( μ**  **g/lb ai) 1**  **Ma xim**  **um Application**  **Rate 2**  **(lb ai/A) Area** 

**Treated or Am**  **ount Handled**  **Daily 3**  **Dermal Inhalation**  **Baseline Baseline**  **Dose (m** **g/k g/day)**  **4 MOE**  **5 Dose**  **(m g/k** **g/day) 6**  **MOE 7**  Mixer/Loader Aerial applications of WDG and Chemigation application of

WDG Artichoke

Persimmon 227 8.96 0.18 350 0.029 170 0.0071 **33** Aerial applications of SC Sugarcane 220 0.219 0.20 1200 0.11 **47** 0.00069 350 Airblast application of WDG Persimmon 227 8.96 0.18 40 0.0033 1,500 0.00081 290 Chemigation application of

WDG and Groundboom application of WDG Greenhouse

tomatoes 227 8.96 0.18 60 0.0050 1,000 0.0012 190 Chemigation applications of SC Sugarcane 220 0.219 0.20 350 0.031 160 0.00019 1,200 Groundboom application of WDG Artichoke 227 8.96 0.18 80 0.0066 750 0.0016 140 Groundboom application of SC Sugarcane 220 0.219 0.20 200 0.018 280 0.00011 2,100 Applicator Aerial application Artichoke Persimmon 5 0.068 0.18 350 0.00064 7,800 0.000054 4,300 Aerial application Sugarcane 5 0.068 0.20 1200 0.0024 2,100 0.00020 1,100 Airblast application Persimmon 1770 4.71 0.18 40 0.026 190 0.00042 540 Groundboom application Greenhouse 78.6 0.34 0.18 60 0.0017 2,900 0.000046 5,000

### Page 54 of 58

**Table E**  **- 1.**  **Occupational Handler Non -**  **Cancer Exposure a nd Risk Estimates for Pyr**  **aclostrobin .**  **Exposure Scenario Crop**  **Dermal Unit Exposure (**  **μ g/lb ai)**  **1 Inhalation Unit** 

**Exposure ( μ**  **g/lb ai) 1**  **Ma xim**  **um Application**  **Rate 2**  **(lb ai/A) Area** 

**Treated or Am**  **ount Handled**  **Daily 3**  **Dermal Inhalation**  **Baseline Baseline**  **Dose (m** **g/k g/day)**  **4 MOE**  **5 Dose**  **(m g/k** **g/day) 6**  **MOE 7**  tomatoes Groundboom application Artichoke 78.6 0.34 0.18 80 0.0023 2,200 0.000071 3,200 Groundboom application Sugarcane 78.6 0.34 0.20 200 0.0064 780 0.00017 1,400 Flagger Flagger Artichoke

Persimmon 11 0.35 0.18 350 0.0014 3,500 0.00028 830 Flagger Sugarcane 11 0.35 0.20 350 0.0016 3,200 0.00031 750 Mixer/Loader/Applicator Backpack application of WDG Greenhouse

tomatoes 13,200 140 0.0018 lb ai/gal 40

gal 0.0019 2,600 0.00013 1,800 Manually pressurized handwand app of WDG Greenhouse tomatoes 100,000 30 0.0018 lb ai/gal 40

gal 0.015 340 0.000027 8,500 Mechanically pressurized handgun of WDG Artichoke Persimmon 1300 3.9 0.0018 lb ai/gal 1000

gal 0.0048 1,100 0.00088 2,600 Mechanically pressurized handgun of WDG Greenhouse tomatoes 3500 120 0.0018 lb ai/gal 1000

gal 0.013 390 0.0027 **85** Mechanically pressurized handgun of WDG Belgium

Endive

– prior to cold storage 1300 3.9 0.000014 lb ai/ lb root 200,000

lb root 0.0074 680 0.00014 1,700 Mechanically pressurized handgun of WDG Belgium

Endive

– prior to forcing 1300 3.9 0.0002 lb ai/ft2 10,890

ft2 0.0057 870 0.00011 2,200

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2013) ; 2 Based on proposed label (See Table 4 ). 3 Exposure Science Advisory Council Policy #9.1. 4 Dermal 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) × DAF (%) ÷ BW (kg). 5 Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day). 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 (kg). 7 Inhalation MOE = I

nhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

### Page 55 of 58

**Table E**  **- 2.**  **Occupational Handler Non -**  **Cancer Exposure a nd Risk Estimates for Pyraclostrobin with PPE**  **. Exposure Scenario**  **Crop Dermal Unit**  **Exposure ( μ**  **g/lb ai) 1**  **Inhalation Unit**

**Exposure ( μ**  **g/lb ai) 1**  **Ma xim**  **um Application**  **Rate 2**  **(lb ai/A) Area** 

**Treated or Am**  **ount Handled**  **Daily 3**  **Dermal Inhalation**  **Baseline + gloves PF5 Respirator**  **Dose (m** **g/k g/day)**  **4 MOE**  **5 Dose**  **(m g/k** **g/day) 6**  **MOE 7**  Mixer/Loader Aerial applications of WDG and Chemigation application of

WDG Artichoke

Persimmon 51.6 1.792 0.18 350 0.0066 760 0.0014 16 0 Aerial applications of SC Sugarcane 37.6 0.0438 0.20 1200 0.018 270 0.00013 1,800 Mixer/Loader/Applicator Mechanically pressurized handgun of WDG Greenhouse tomatoes 2500 24 0.0018 lb ai/gal 1000

gal 0.0091 550 0.00054 430 1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2013) ; 2 Based on proposed label (See Table 4 ). 3 Exposure Science Advisory Council Policy #9.1. 4 Dermal 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) × DAF (%) ÷ BW (kg). 5 Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day). 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 (kg). 7 Inhalation MOE = I nhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

### Page 56 of 58

**T able**  **E -**  **3. Occupational Post** **- application**  **Non -**  **Cancer Exposure and Risk Estimates for Pyraclostrobin**  **. Crop/Site**  **Activities Transfer**  **Coefficient (cm** **2 /hr)**  **DFR 1**  **Derm al Dose**  **(m g/kg/day)**  **2 MOE**  **3**
Sugarcane Scouting 1,100 0.152 0.0027 1,800 Hand Harvesting 17,600 0.043 120 Hand Weeding 70 0.00017 29,000

Artichoke Hand Harvesting 1,100
0.379 0.0068 740

Hand Weeding, Thinning, Pruning 70 0.00043 12,000

Irrigation (hand set) 1,900 0.012 430 Scouting 210 0.0013 3,900 Transplanting 230 0.0014 3,500

Persimmon Scouting, Hand pruning, Training 580
0.686 0.0065 770

Hand weeding, Propping, orchard

maintenance 100 0.0011 4,500 Hand Harvesting 1,400 0.016 320 Transplanting 230 0.0026 2,000 Thinning 3,600 0.040 120 Greenhouse Tomatoes Hand harvesting, pinching, hand pruning,

Scouting, Turning, T yi ng, Hand weeding, 1200 0.379 0.0074 680 Irrigation (hand watering), Transplanting 230 0.0014 3,500 1 DFR chemical
- specific study ( see Appendix D, Tables D4, D5, and D6 ) 2 Daily Dermal Dose = [DFR (μg/cm2 ) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption (%)]  BW (kg). 3 MOE = POD (mg/kg/day) / Daily Dermal Dos e. Daily Dermal Dose = [DFR (μg/cm2 ) 

### × TC 

### × 0.001 mg/μg 

### × 8 hrs/day 

### × dermal absorption factor (%) ]  BW (kg)
.

### Page 57 of 58

**Appendix F.**  **Summary of Pyraclostrobin DFR Study Results Table**  **F -**  **1 . Summary of DFR Values and Regression Analysis Results for Treated Peach Foliage with**  **Pyraclostrobin**

Input/Parameter Georgia Pennsylvania California Application Rate (lb ai/A) (Study Target Rate = 0.12 lb ai/A) 0.12 0.12 0.12 Spray Volume (GPA) 105 92.2 152 Measured Average Day 0 Residue (μg/cm2 ) 0.175 0.29 0.29 Predicted Day 0 Residue (μg/cm2 ) 0.176 **0.457** 0.389 Slope
- 0.0963
- 0.105
- 0.0297 Half
- life (days) 7.2 6.6 23 R2 0.98 0.90 0.59
**Table F**  **- 2**  **. Summary of DFR Values and Regression Analysis Results for Treated Strawberry Foliage with Pyraclostrobin** 

Input/Parameter North Carolina California Oregon Application Rate (lb ai/A) (Study Target Rate = 0.18 lb ai/A) 0.18 0.18 0.18 Spray Volume (GPA) 45.8 45.8 45.8 Measured Average Day 0 Residue (μg/cm2 ) 0.505 0.431 0.19 Predicted Day 0 Residue (μg/cm2 ) 0.1 **0.379** 0.0963 Slope
- 0.139
- 0.166
- 0.106 Half
- life (days) 5 4.2 6.5 R2 0.62 0.99 0.85
**Table F -**  **3. Summary of DFR Values and Regression Analysis Results for Treated Peanut Foliage with**  **Pyraclostrobin**

Input/Parameter Texas Georgia North Carolina Application Rate (lb ai/A) (Study Target Rate = 0.25 lb ai/A) 0.25 0.25 0.25 Spray Volume (GPA) Not provided Not provided Not provided Measured Average Day 0 Residue (μg/cm2 ) 0.497 0.438 0.511 Predicted Day 0 Residue (μg/cm2 ) **0.19** 0.104 0.133 Slope
- 0.122
- 0.104
- 0.112 Half
- life (days) 5.7 6.7 6.2 R2 0.78 0.46 0.63 Note: Bolded text indicates DFR values used in exposure assessments.

### Page 58 of 58

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



## Pyraclostrobin ( 099100; 02/19/2013 ) Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 

### Codex 3 40 CFR §180.582. Plants: Tolerances are established for residues of the fungicide pyraclostrobin, including its metabolites and degradates. Compliance with the tolerance levels is to be determined by measuring on the sum of pyraclostrobin (carbamic acid, [2
- [[[1
- (4
- chl orophenyl)
- 1 H

- pyrazol
- 3
- yl]oxy]methyl]phenyl]methoxy
- , methyl ester) and its desmethoxy metabolite (methyl N
- [[[1
- (4
- chlorophenyl)
- 1 H

- pyrazol
- 3
- yl]oxy]methyl]phenyl carbamate), calculated as the stoichiometric equivalent of pyraclostrobin
. methyl [2
- [[[1
- (4
- chlorophenyl)
- 1 H

pyrazol
- 3
- yl]oxy]methyl]phe nyl]methoxycarba mate, including the metabolite [2
- [[[1
- (4
- chlorophenyl)
- 1 H
- pyrazol
- 3
- yl]oxy]methyl]phe nyl]carbamate - Py raclostrobin. Residue is NOT fat soluble.



### Commodity 1 

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

### Codex 3 Artichoke, globe 3.0 None 2. Belgium endive (witloof chicory) 4.0 None None Persimmon 3.0 None None Vegetable, bulb, group 3
- 07 0.9 0.9 Garlic 0.15 Leek 0.7 Bulb onion 1.5 Spring onion 1.5 Vegetable, fruiting, group 8
- 10 1.4 Tomato 1 Pepper 1 Tomato 0.3 Pepper 0.5 Eggplant (aubergine) 0.3 Fruit, citrus, group 10
- 10 2.0 2.0 2 Fruit, pome, group 11
- 10 1.5 1.5 Apple 0.5 Oilseed group 20 0.45 0.45 0.4 Caneberry subgroup 13
- 07A 4.0 3.5 Blackberry 3 Bushberry subgroup 13
- 07B 4.0 3.5 Blueberry 4 Small fruit, vine climbing subgroup (except fuzzy kiwi) 13
- 07F 2.0 2.0 Grape 2 Lo w growing berry subgroup 13
- 07G except cranberry 1.2 1.2 Straw berry 1.5

1 Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and not those proposed by the applicant.
2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes. 3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.