Page **1** of **46** UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460 **OFFICE OF CHEMICA** **L SA FETY**  **AND POLLUTION PREVENTION**  **MEMORANDUM D**  **ATE :**  March 12 , 201 5 **SUBJECT: Pyraclostrobin** 

– Human Health Risk Assessment for a Section 3 Registration of

N ew U ses on Herb Subgroup 19A and Dill Seed , Plus Crop Group Conversions on Stone Fruit Group 12
- 12 and Tree Nut Group 14
- 12. **PC Code:**  099100 **DP Barcode:** D 416700 **Decision No.:** 484923 **Registration No. :**  7969
- 199 **Petition No .:**  3E8216 **Regulatory Action:** Section 3 Registration **Risk A**  **ss essment Typ**  **e :**  Single Chemical/Aggregate **Case No.:** 7034 **T XR No.:**  NA **CAS No.:** 1 7 5 013
- 1 8
- 0 **MRID No.:** NA **40 CFR:** 180.58 2 **FROM:** Barry

O’Keefe , Senior Biologist Vincent Chen , Toxicologist 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:** Andrew Ertman , Risk Manager

Risk Integration, Minor Use and Emergency Response Branch (RIMUERB) Registration Division (7505P) This document and attachments provide an assessment of the human health risk resulting from the proposed and registered uses of py raclostrobin
. The toxicology reevaluation was performed by Vincent Chen , the drinking water assessment was conducted by Edom Seifu (EPA Environmental Fate and Effects Division (EFED)), the review of the residue chemistry data an d dietary exposure assessment w ere conducted b y Steve Funk, the occupational and residential exposure assessment was conducted b y Cassi Walls , and the human health risk assessment w as conducted b y Barry

O’Keefe
.Page **2** of **46 Table of Contents**  **1.0 Executive Summary** 
................................ ................................ ................................ ........... 4 **2.0 HED Recommendations** 
................................ ................................ ................................ .... 7 **2.1 Da** **ta Deficiencies**
................................ ................................ ................................ ............ 7 **2.2.1 Enforcement Analytical Method** 
................................ ................................ ............... 7 **2.2.2 Recommended Tolerances** 
................................ ................................ ......................... 8 **2.2.3 Revisions to Petitioned**  **- For Tolerances** 
................................ ................................ .... 8 **2.2.4 International Harmonization** 
................................ ................................ ..................... 8 **2.2.5 Label Recommendations** 
................................ ................................ ............................ 9 **3.0 Introduction** 
................................ ................................ ................................ ........................ 9 **3.1 Chemical Identity** 
................................ ................................ ................................ ........... 9 **3.2 Phys**  **ical/Chemical Characteristics**
................................ ................................ ............... 9 **3.3 Pesticide Use Pattern** 
................................ ................................ ................................ .... 10 **3.4 Anticipated Exposure Pathways** 
................................ ................................ ................. 10 **3.5 Consideration of Environmental Justice** 
................................ ................................ .... 11 **4.0 Hazard Characterization and Dose**  **- Response Assessment** 
................................ .......... 11 **4.1 Summary of Toxicological Effects** 
................................ ................................ .............. 11 **4.2 Safety Factor for Infants and Children (FQPA Safety Factor)** 
............................... 12 **4.2.1 Completeness of the Toxicology Database** 
................................ .............................. 12 **4.2.2 Evidence of Neurotoxicity** 
................................ ................................ ........................ 12 **4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal** 
........ 13 **4.2.4 Residual Uncertainty in the Exposure Database** 
................................ ................... 13 **4.3 Toxicity Endpoint and Point of Departure Selections** 
................................ .............. 13 **4.3.1 Dose**  **- Response Assessment** 
................................ ................................ ...................... 13 **4.3.2 Cancer Classification and Risk Assessment Recommendation** 
............................ 15 **4.3.3 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk**  **Assessment**
................................ ................................ ................................ ............................... 16 **5.0 Dietary Exposure and Risk Assessment** 
................................ ................................ ......... 18 **5.1 Residues of Concern Summary and Rationale** 
................................ .......................... 18 **5.2 Food Residue Profile** 
................................ ................................ ................................ .... 18 **5.3 Water Residue Profile** 
................................ ................................ ................................ .. 19 **5.4 Dietary Risk Assessment** 
................................ ................................ .............................. 20 **5.4.1 Description of Residue Data Used in Dietary Assessment** 
................................ .... 20 **5.4.2 Percent Crop Treated Used in Dietary Assessment** 
................................ .............. 20 **5.4.3 Acute Dietary Risk Assessment** 
................................ ................................ ............... 21 **5.4.4 Chronic Dietary Risk Assessments** 
................................ ................................ ......... 21 **5.4.5 Summary Table** 
................................ ................................ ................................ ......... 21 **6.0 Residential (Non**  **- Occupational) Exposure/Risk Characterizatio**  **n** ............................. 22 **6.1 Residential Bystander Post**  **- application Inhalation Exposure** 
................................ . 22 **6.2 Spray Drift** 
................................ ................................ ................................ .................... 23 **7.0 Aggregat**  **e Exposure/Risk Characterization**
................................ ................................ .. 23 **7.1 Acute Aggregate Risk** 
................................ ................................ ................................ ... 23 **7.2 Short** **- Term Aggregate Risk** 
................................ ................................ ........................ 24 **7.3 Chronic Aggregate Risk** 
................................ ................................ .............................. 24 **8.0 Cumulative Exposure/Risk Characterization** 
................................ ............................... 24Page **3** of **46**

**9.0 Occupational Exposure/Risk Characterization** 
................................ ............................ 25 **9.1 Short** **- /Intermediate**  **- Term Handler Risk** 
................................ ................................ ... 25 **9.2 Short** **- and Intermediate**  **- Term Post**  **- Application Risk** 
................................ .............. 26 **9.2.1 Dermal Post**  **- Application Risk** 
................................ ................................ ................. 26 **9.2.2 Inhalation Post** **- Application Risk** 
................................ ................................ ............ 26 **10.0 References** 
................................ ................................ ................................ ......................... 28 **Appendix A. Toxicology Profile and Executive Summaries**
................................ .................. 29 **A.1 Toxicology Data Requirements** 
................................ ................................ ................... 29 **A.2 Toxicity Profiles** 
................................ ................................ ................................ ............ 30 **Append ix B. Methodologies for Human**  **- Equivalent Concentration (HEC) Calculations.** 
.. 36 **Appendix C. Physicochemical Properties of Pyraclost robin.** 
................................ ................ 41 **Appendix D. Review of Human Research**
................................ ................................ ................ 42 **Appendix E. Occupational Handler and Post -**  **application Exposure and Risk Estimates**
.. 43 **Appendix F. Summaries of Field Residue Data**
................................ ................................ ...... 45 **Appendix G. International R esidue Limits Status Sheet** 
................................ ....................... 46Page **4** of **46**

**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, on residential and golf course turf, residential ornamentals, landscape gardens, residential fruit and nut trees, and greenhouse grown tomato transplants for the home consumer market. Use Profile The Interregional Research Project No. 4 (IR
- 4) is proposing new use s on herb subgroup 19A and dill as additions to the Pristine ® Fungicide label (EPA Reg. No. 7969
- 199). Additionally , IR
- 4 is proposing crop group conversions for the stone fruit group 12
- 12 and the tree nut group 14
- 1 2
. The Pristine ® Fungicide label also includes the active ingredient boscalid ; therefore, a separate HED exposure and risk assessment document will be completed to evaluate the proposed new uses and crop conversions for boscalid
. The Pristine ® label require s occupational handlers to wear the following personal protective equipment (PPE): long
- sleeved shirts, long pants, shoes , socks, and chemical resistant gloves. The 12 hour restricted entry interval (REI) listed on the label is adequate to protect workers
. Exposure Profile Exposure pathways include dietary (food and drinking water), residential, and occupational exposure sources. Dietary exposures are expected for acute and chronic durations. Existing residential u se s result in short
- term handler dermal and inhalation expo sures for adults, and short
- term post - application dermal exposures for adults, youths (11 to 16 years old), children 6 to 11 years old , and children 1 to <2 years old
. Additionally , existing residential uses result in short
- term incidental oral exposures to children 1 to <2 years old. Occupational handler and post - application exposures are expected via dermal and inhalation routes for short
- and intermediate
- term durations. Hazard Assessment The primary

target tissues following repeated p yr aclostrobin e xposure appear to be mucosal membranes, with histopathology or secondary

effects (e.g., diarrhea) observed in different species. The primary

effects were decreased body weight and food consumption in addition to diarrhea. The developmental study in rabbits indicated qualitative susceptibility where increased fetal resorptions, post
- implantation loss, and total resorptions occurred at the same doses as maternal effects (i.e., decreased food consumption and food efficiency); however, toxicity endpoints and traditional UFs are protective of these effects and therefore, the degree of concern for prenatal and postnatal toxicity is low. This assessment use s the results from a new inhalation toxicity study
. Py

raclostrobin is classified as “Not Likel y to be Carcinogenic to Humans.” There was no observed 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 inci dental oral, and short
- and intermediate
- term dermal and inhalation exposure scenarios. The toxicity of py raclostrobin through the inhalation routePage **5** of **46**

predominatel y consist ed of portal of entry (POE) effects ; therefore, a Human Equivalent Dose (HED) and a Human Equivalent Concentration (HEC) have been used to assess inhalation risks
. The Food Quality

Protection Act (FQPA) Safety Factor (SF) 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. Py raclostrobin has moderate to low acute toxicity via the oral, dermal, and inhalation routes of exposure. Py

raclostrobin is a mild dermal and eye irritant. Py raclostrobin is not a dermal sensitizer. Dietary Exposure The residue chemistry

and environmental fate data are adequate to assess human dietary exposure . The assessments are based on reliable data and will not underestimate exposure or risk. E stimated drinking water concentrations (EDWCs) were incorporated directly into the dietary exposure assessments. The results of the partially refined acute dietary (food and drinking water) anal ys is using tolerance level residues 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. For children 1 to 2 years old, the population subgroup with the highest exposure for this aPAD, exposure is equivalent to 2.8% of the aPAD. Additionally , the population subgroup females 13 to 49 ye ars old are assessed with a different aPAD and have the highest estimated acute dietary

risk estimate, with an estimated exposure at the 95 th percentile of 87% 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. population is 8. 1 % of the chronic Population Adjusted Dose (c PAD) and 27% of the cPAD for children 1
- 2 years old , the population subgroup with the highest estimated chronic dietary exposure to py

raclostrobin. Resid ential Exposure N o n ew residential uses were requested in this action
. However, py raclostrobin is currently registered for use on residential and gol f course turf , residential ornamentals and landscape gardens, and residential fruit and nut trees
. Residential exposure is expected to be short
- term only
. Residential exposure s from these existing residential use s w ere previously assessed 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 margins of exposure (MOEs) rang ing from 590 to 3,9 00,000 (LOCs <100). The only new residential exposure assessment conducted in this current document was for handler inhalation exposure from a ppl ying WDG formulation to turf via manually pressurized handwand or backpack sprayer using the results from the new inhalation toxicity study and using HEDs/HECs. This was from the previous highest exposure risk estimate MOE of 590, and using the HED /HEC method
1 http://www.epa.gov/pesticides/science/residential
- exposure - sop.htmlPage **6** of **46**

resulted in an MOE of 97 (LOC <30), which is still not of concern . All previously assessed residential post
- application dermal and incidental oral exposure risk estimates were also not of concern to HED, with MOEs ranging from 150 to 34 0,000. Aggregate Exposure There is potential for acute, short
- term , and chronic aggregate exposure to py raclostrobin
. The short
- term aggregate exposure results from dietary (which is considered background exposure) and residential (which is considered primary) exposure pathways. The acute and chronic aggregate exposure s are the same as acute and chronic dietary exposure s from food and drinking water, which are all below the HED’s level of concern. The adult short
- term aggregate MOE is 230, which includes post
- application exposure to treated turf and background dietary exposure and is not of concern to HED. The short
- term aggregate MOE for children 1
- 2 years old, including incidental oral exposures from treated turf and background dietary exposure , is 1 1 0, which is not of concern to HED. The short
- term aggregate MOE for children 6
- 11 years old, including post
- application dermal exposures from treated gardens and background dietary exposure, is 3 8 0, which is not of concern to HED. The short
- term aggreg ate MOE for youths 11
- 16 years old, including post
- application dermal exposures from treated turf from golfing and background dietary

exposure, is 1, 6 00, which is not of concern to HED. Occupational Exposure Based on the proposed agricultural use s , there is potential for short
- and intermediate
- term occupational exposure during handling and post
- application activities. The proposed label require s occupational handlers to wear the following PPE: long
- sleeved shirts, long pants, shoes , socks, and chemical resistant gloves. The dermal MOEs range from 63 (mixing/loading/applying of WG formulation to support mechanically

pressurized handgun applications) to 2, 6 00 ( ground application to herbs) at baseline PPE. When assessed with labelled PPE (e.g., including gloves), all dermal MOE s are ≥210. Since all dermal MOEs at labelled PPE are greater than the LOC of 100, they are not a concern to HED. The inhalation MOEs range from 34 (mixing/loading of WG formulation to support ground applications to dill se ed) to 1 ,1 00 ( ground application to herbs) at baseline PPE (no respirator). A ll handler scenario MOEs at labelled PPE (e.g., no respirator) are greater than the LOC of 30 , which are not a concern to HED. All post
- application scenarios resulted in dermal MOEs greater than 100 on day 0 (12 hours after application) and therefore are not of concern to HED . The MOEs for py raclostrobin ranged from 380 to 10 ,000. DFR studies are not re quired at this time for py raclostrobin since the lowest dermal MOE ( 38 0 ) is greater than 2 times the LOC based on default input values. Based on the Agency's current practices, a quantitative occupational post
- application inhalation exposure assessment was not performed for p yr aclostrobin at this time. I f new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post - application inhalation exposure assessment for py raclostrobin
. The 12 hour RE I listed on the label is appropriate.Page **7** of **46**

Review of Human Research This risk assessm ent 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 Outdoor Residential Exposure Task Force (ORETF) , and the Residential SOPs (lawns and turf) are subject to ethics review pursuant to 40 CFR 26, have received that review, and are compliant with applicable ethi cs requirements. For certain studies that review may have included review by the Human Studies Review Board. Descriptions of data sources as well as guidance on their use can be found at http://www.epa.gov/pesticides/science/handler
- exposure - data.html and http://www.epa.gov/pesticides/science/post
- app - exposure - data.html
. Environmental Justice Considerations Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Pop ulations and Low - Income Populations," (http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf
. **2.0 HED**  **Recommendations** HED has examined the toxicology , residue chemistry , and exposure database s for py raclostrobin
. Pending submission of a revised Section F, there are no toxicology or residue chemistry

issues that would preclude granting Section 3 registration for the requested uses of py raclostrobin , or establishment of tolerances for residues of py raclostrobin
. No additional data are needed
. The specific tolerance recommendations a re discussed in Section 2.2
. **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. The anal ytical methods for plant commodities are liquid chromatography with tandem mass spectrometry (L C/MS/MS ; BASF Method D9908 ) and high pressure liquid chro matography with ultraviolet detector ( HPL C/UV ; BASF Method D9904 ) , which both measure p yr aclostrobin and its desmethox y metabolite (BF 500
- 3)
. The validated method limit of quantitation ( 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 submitted for both methods. The anal ytical methods for livestock commodities , gas chromatography with mass spectrometry (GC/MS ) and L C/MS /MS, convert p yraclostrobin and related metabolites toPage **8** of **46**

chlorophenylpy

razolol (BF 500
- 5) and hydrox yl ated chlorophenylpy razolol (BF 500
- 8) in goats and chlorophenylpy

razolol (BF 500
- 5) and a hydroxylated chlorophenylpyrazolol isomer of BF 500
- 8 (BF 500
- 9) in poultry
. **2.2. 2**  **Recommended Tolerances** Sufficient data are available to support tolerances for residues of the fungicide py raclostrobin , including its metabolites and degradates, in or on dill seed and the herb subgroup 19A. The tolerance expression is aligned with the requirements of the S. Knizner 05/27/2009 memo. A summary of the proposed and recommended tolerances may be found in Table 2.2.2 below. **Table 2.2.2**  **. Tolerance Summary for Pyraclostrobin** 

**Comm odity**  **Proposed Tolerance**  **(ppm) Existing** 

**Tolerance HED** 

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

**( correct commodity**  **definition )**  Herb subgroup 19A 85
- 40 Dill, seed 100
- 40 Fruit, stone, group 12 2.5 Revoke Crop group conversion Fruit, stone, group 12
- 12 2.5
- 2.5 Crop group conversion Nut, tree, group 14 0.04 Revoke Crop group conversion Nut, tree, group 14
- 12, except pistachio 1 0.04
- 0.04 Crop group conversion 1 A separate tolerance exists for pistachio (0.7 ppm). **2.2. 3**  **Revisions to Petitioned -**  **For Tolerances** The proposed tolerances for the herb subgroup 19A and dill seed are based on the use of field trial data without adjustment for the exaggerated application rate (2.7X) represented b y those trials. Each of the two applications of py raclostrobin were conducted at 2.7X the label rate, and the total seasonal rate was 2.7X the label rate. Using the assumption of proportionality , i.e., that the residue levels are proportional to the rate of application, the residue results may be adjusted to the concentrations exp ected at the 1X rate. The tolerance estimates at the 1X rate are 40 ppm for herb subgroup 19A and 40 ppm for dill seed. A revised section F must be submitted. **2.2. 4**  **International Harmonization** The Codex and US residue definitions for p yraclostrobin residues on plant commodities are different. The Codex definition is py raclostrobin, whereas the US definition is py raclostrobin and its desmethox y metabolite. Codex has not established MRL s for py raclostrobin on herbs or dill seed, and therefore there are no harmonization issues. Codex has established MRL s for some members of the stone fruit group, i.e., cherries (3 mg/kg), peach/nectarine (0.3 mg/kg), and plums (0.8 ppm), but does not have a group tolerance. Codex has established a tree nut group tolerance at 0.02 mg/kg. The US tolerance cannot be lowered, as it includes parent and a metabolite, each at 0.02 ppm, or 0.04 ppm total. The Canada and US definitions for the py raclostrobin residue are harmonized. Canada has not established MRL s for herbs or dill seed. Canada has MRL s for tree nuts, and these are harmonized with the US. Canada has established MRL s for various stone fruits at 0.7 ppm. ThePage **9** of **46**

US tolerance for stone fruits prior to 2009 was 0.9 ppm. However, the tolerance was increased to 2.5 ppm to accommodate European Union import requirements (D359194, M. Negussie, 04/01/2009; PP#8F7390). Refer to Appendix G for the International Residue Limits status table
. **2.2. 5**  **Label Recommendations**  None. **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 sporulation of the fungus on the leaf surface. Py raclostrobin is currently

registered on numerous agricultural crops, as well as s eed treatment use on o ats, c anola, and f lax . Additionally, it is registered for use on residential and golf course turf , residential fruit and nut trees , residential ornamentals and landscape gardens , and tomato transplants grown for the home consumer market
. With the current action , IR
- 4 is proposing new use s on herb subgroup 19A and dill seed as additions to the Pristine ® Fungicide label (EPA Reg. No. 7969
- 199). Additionally , IR
- 4 is proposing crop group conversions for the stone fruit group 12
- 12 and the tree nut group 14
- 1 2
. **3.1 Chemical Identity**  The chemical structure and nomenclature of py raclostrobin is presented in Table 3.1. **T able**  **3.1. Pyraclostrobin 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) Pristine® Fungicide, EPA Reg. No. 7969
- 199 **3.2 Physical/Chemical Characteristics**  Py raclostrobin has a log octanol/water partition coefficient (log Kow) of 3.99
. P yraclostrobin 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 1.9×10 - 8 mm Hg at 20 oC limiting N N Cl O N O C H 3 O OCH 3Page **10** of **46**

the potential for volatilization. The physiochemical properties of py raclostrobin are summarized in Appendix C
. **3.3 Pesticide Use Pattern**  **Note: An updated label was received; and therefore, the use pattern assessed in the occupational and residential exposure chapter and in the residu**  **e chemistry summary document are different**  **from this comprehensive risk assessment document . Applications**  **by chemigation and aerial methods were removed on the updated label.** Interregional Research Project No. 4 (IR
- 4) is proposing new use s of py raclostrobin on herb subgroup 19A and dill seed as additions to the Pristine ® Fungicide label (EPA Reg. No. 7969
- 199). Pristine ® Fungicide is a multiple active ingredient water dispersible granule (WDG) fungicide containing 12.8% py raclostrobin and 25.2% boscalid. Herbs and dill may be treated at a maximum single application rate of 0. 15 lb ai/A (18.5 fl oz/A) using ground application equipment. Pristine ® Fungicide may be applied two times per year at a maximum yearl y application rate of 0. 3 lb ai/A (37 fl oz/A). The label requires occupational handlers to wear the following PPE: long
- sleeved shirts, long pants, shoes and socks, and chemical resistant gloves. The 12 hour REI listed on the label is app ropriate. Additionally , IR
- 4 is proposing crop group conversions for the stone fruit group 12
- 1 2 and the tree nut group 14
- 1 2
. The proposed uses of py

raclostrobin are summarized in Table 3.3
. **Table 3.3. Summary of Directions for the Proposed Uses of**  **Py raclostrobin**  **.**
**Use Site Application** 

**Me thod**  **Maximum**

**Single Application**  **Rate (lb ai/A)**  **Maximum**

**Number of Applications** **/ Year**  **Maximum**

**Application Rate/Acre/**  **Year (lb ai/A/yr)**  **Minim um** 

**Retreatm ent**  **Interval (days)**  **PHI**

**(days)**
Herb Subgroup Ground 0. 15 2 0. 3 7 0 Dill Seed 0. 15 2 0. 3 7 0 **3.4 Anticipated Exposure Pathways**  Humans may

be exposed to py

raclostrobin in food and drinking water, since py raclostrobin may be applied directly

to growing crops and application may result in py

raclostrobin reaching surface and ground water drinking water sources . There are existing residential uses of py raclostrobin 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
.Page **11** of **46**

Risk assessments have been completed for proposed and existing uses of py racl ostrobin . This risk assessment considers all of the aforementioned exposure pathways based on the proposed new uses of py

raclostrobin , but also considers existing uses of py raclostrobin , 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 Ameri ca, (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 , specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, non
- dietary

exposures based on home use of pesticide products and associated risks for adult applicators and for toddlers, youth s, 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 mitochon drial 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 S**  **ummary of Toxicological Effects** The most consistently

observed effects of py

raclostrobin exposure across species, genders, and treatment durations were diarrhea , decreased body weight, and decreased f ood consumption
. Py raclostrobin 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 by redness and chemosis (i.e., swelling of the conjunctiva) seen in the primary eye irritation study
. In the rat acute and subchronic neurotoxicity studies, neuropathology

and behavior changes were not observed.Page **12** of **46**

In the rat and rabbit developmental toxicity studies, developmental toxicity (i.e. skeletal variations, post
- implantatio n loss, and fetal resorption) occurred at doses greater than or equal to those doses causing maternal toxicity (i.e. diarrhea , decreased body weight , food consumption, and clinical signs of toxicity)
. In the reproduction study , s ys temic toxicity manifeste d as decreased body weight in both the parents and offspring ; no reproductive or offspring toxicity was observed. In the rat subchronic inhalation toxicity studies , inhalation toxicity consisted of both portal of entry effects (i.e., olfactory

atrophy /ne crosis and histiocy

tosis in the lungs) and systemic effects (i.e., hy perplasia in the duodenum). Py raclostrobin was classified by the Cancer Assessment Review Committee (CARC) as “Not Likel y to be Carcinogenic to Humans” based on the lack a of treatment
- related increase in tumor incidence in adequatel y conducted carcinogenicity studies in rats and mice (CARC , 02/15/2007, TXR0054516)
. Py

raclostrobin did not cause mutagenicity or genotoxicity

in the in vivo and in vitro assays. Py

raclostrobin did not cause immunotoxicity in T
- cell dependent antibody response (TDAR) or Natural Killer (NK) assay s in mice. Py raclostrobin has moderate to low acute toxicity via the oral, dermal, and inhalation routes of exposure ( Toxicity

Categories II
- IV). Py

raclostrobin is a mild dermal and eye irritant ( Toxicity Category III) . Py raclostrobin is not a dermal sensitizer. **4. 2**  **Safety Factor for Infants and Children (FQPA Safety Factor)** For all asses sment scenarios, the 10 x FQPA Safety Factor can be reduced to 1 x because the to xicity 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 .2.1**  **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. **4.2.2 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 be a reflection of the perturbations in mitochondrial respiration leading to effects on energy production. In the absence of definitive neurotoxicity or neuropathology

findings in the neurotoxicity battery or elsewhere in the database, a developmental neurotoxicity study is not required.Page **13** of **46**

**4.2.3 Evidence o**  **f Sensitivity/Susceptibility in the Developing or Young Animal** There is no concern for pyraclostrobin causing an increased susceptibility in in utero rats or rabbits in the prenatal developmental studies or in young rats in the 2
- generation reproduction s tudy
. Although there is some concern for qualitative susceptibility in the prenatal development study in rabbits the toxicity

endpoints and traditional UFs are protective of these effects
. The degree of concern for prenatal and postnatal toxicity is low. **4.2.4 Residual Uncertainty in the Exposure Database**  There are no residual uncertainties identif ied in the exposure databases. The acute dietary exposure assessments were performed assuming 100% of the crops were treated with py raclostrobin and incorporating 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) assumption s in the ground and surface water modeling used to assess exposure to py raclostrobin in drinking water. Although the acute and chronic assessments included minor refinements, the use of field trial and %CT estimates ensures that actual exposures/risks from residues in food will not be underestimated. EPA used similarly conservative assumptions to assess post
- application exposure of adults and children
. The residential exposure assessment is based on the updated 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 applicati on rate. These data are reliable and are not expected to underestimate risks to adults or children. The Residential S OPs are based upon reasonable “worst
- case” assumptions are not expected to underestimate risk. Although some of the residue values used in the dietary exposure assessment were refined, these assessments will not underestimate the exposure to p yr aclostrobin. **4.3 Toxic**  **ity Endpoint and Point of Departure Selections 4.3.1**  **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, a new 28
- day inhalation study in rats w as used for 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. For acute dietary

(general population) risk assessment, the point of departure (POD) is based on decreased body weight gain in males at the lowest observable adverse effect level (LOAEL) of 1,000 mg/kg/day

seen in the acute neurotoxicity study ( no observable adverse effect level NOAEL) of 300 mg/kg/day). This selected endpoint is appropriate for acute dietary risk assessment because the decreased body weight gain (33%) in males occurred during the first week after administration of the highest dose of 1000 mg/kg.Page **14** of **46**

For acute dietary

(females 13
- 49), and short
- and intermediate
- term dermal exposures, the POD is based on increased resorptions/post
- implantation loss at the LOAEL of 10 mg/kg/day are assumed to occur following a single in utero exposure in the rabbit developmental toxicity study
. These effects were dose
- dependentl y increased at the next and highest dose tested of 20 mg/kg/day. Additionally, the maternal 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 dermal absorption factor of 14% will be applied to the dermal exposure assessments. For chronic dietary , th e POD is based on decreased body weight and kidney

tubular casts/atrophy in both sexes , and liver necrosis and stomach lesions in males at the high est dose tested (LOAEL) of 9.2 mg/kg/day (NOAEL of 3.4 mg/kg/day)
. For short
- and intermediate
- term in cident al oral exposures , the POD is based on 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 in the s ubchronic toxicity study in the dog (NOAEL of 5.8 mg/kg/day)
. The short
- and intermediate
- term inhalation POD s were derived from a route - specific 28
- day inhalation study

in rats where the NOAEL is 0.0 1 0 mg/L/day ; the LOAE L is 0.0 30 mg/L/day for both sexes based on olfactory atrophy /necrosis in the nasal tissues
. In another subchronic inhalation study , the LOAEL at 0.0 3 0 mg/L/day for both sexes was based on findings of hy perplasia in the duodenum, alveolar histiocy tosis in the lungs, and olfactory atrophy /necrosis in the nasal tissues
. Inprevious risk assessments, HED converted the NOAELand LOAEL values from mg/L/day

into mg/kg/day

in rats onl y. However, HED’s standard operating procedure for the assessment of inhalation exposures have changed since the last risk assessment to account for rat
- human pharmacokinetic differences thereby reducing uncertainty

from 100 x to 30 x . Refinements were conducted to better match hazard reference values with exposure estimates for a more accurate estimation of inhalation risk. Therefore, HED is trans lating an inhalation hazard reference concentration to a daily dose estimate for more accurate risk characterization. Adjustments for species differences in breathing rates, respiratory tract architecture, and deposition fraction (aerosols) have been made
. The methods and dosimetry equations described in EPA’s RfC guidance (1994) are suited for calculating HECs based on the inhalation toxicity N OAEL for use in MOE calculations. The regional deposited
- dose ratio (RDDR), which accounts for the particulate diameter (mass median aerodynamic diameter [MMAD] and geometric standard deviation [  g ] of aerosols), can be used to estimate the different dose fractions that are deposited along the respiratory tract. The RDDR is also based on interspecies differences in ventilation and respiratory
- tract surface areas. Thus, the RDDR can be used to adjust an observed animal particulate inhalation exposure to the predicted inhalation exposure for a human. For the 4
- week inhalation study with py raclostrobin, an RDDR wa s estimated at 0.1 31 based on the reported MMAD of 2
. 20 μm and standard deviation (  g) of 3
. 7 0 and the respiratory
- tract surface area of the rat relative to the human (see Appendix B for detailed calculations). Since the rat inhalation study was carried out for 6 hr/day for 5 days/week, the onl y exposure adjustment made was in the assumption of 8 hr/day forPage **15** of **46**

human occupational exposures. The resulting HECs for residential and occupational exposures are presented in Tables 4.3. 4. 1 and 4.3. 4. 2. The LOC is 30 , which includes interspecies (3 x ) and intraspecies (10 x ) uncertainty factors. The interspecies factor was reduced from 10 x to 3 x due to the HEC calculation accounting for pharmacokinetic interspecies differences , but the intraspecies factor is retained at 10 x because HEC calculation does not account for pharmacodynamic intraspecies differences
. Using the reference concentration (RfC) methodology , human
- equivalent concentrations (HECs) and human
- equivalent doses (HEDs) were generated for residential and oc cupational inhalation risk assessments. HECs were derived from th e 28
- day inhalation study in rats based upon th e portal of entry

effects in the extrathoracic (ET) region (i.e., olfactory atrophy /necrosis in the nasal tissues) which is considered a portal
- of
- entry effect and is protective for any s ys temic effects (HEC = 0.0 0098 mg/L for occupational handlers and HEC = 0.0 0131 mg/L for residential handlers )
. HEDs were subsequently calculated for occupational handler exposure scenarios based upon ventilation rates of 8.3, 16.7, and 29 L/min ( 0.056, 0.113, and 0.195 mg/kg/day , respectivel y) and residential
- handler exposure scenarios based upon a ventilation rate of 16.7 L/min ( 0.038 mg/kg/day). For details regarding the calculation of the HECs and HEDs, see Appendix B. These HEDs are protective of the portal of entry and systemic effects observed through the inhalation route. This study is thus appropriate for the route and duration of exposure, and is protective of adults in occupational and residential settings. **4.3. 2**  **Recommendation for Combining Routes of Exposure for Risk Assessment** When there are potential residential exposures to a pesticide, aggregate risk assessment must consider exposures from three major sources: oral, dermal and inhalation exposures. 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 residential 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 mg/kg/day ; this more relevant end point 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 increased incidence of diarrhea, clini cal chemistry changes, duodenum mucosal hy

pertrophy , and decreased body weight and food intake/efficiency at the LOAEL of 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 dermal and incidental oral exposures for toddlers were combined
. For occupational handlers, dermal and inhalation exposures were not combine d, because there are no common endpoints.Page **16** of **46**

**4.3. 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 , 02/15/2007, TXR0054516 ). **4.3. 3**  **Summary of Points of Departure and Toxicity Endpoints Used in Human Risk Assessment** 
**Table 4.3. 3**  **.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, 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 months) 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 efficiency. Dermal Short Term (1
- 30 days) Intermediate Term (1
- 6 months) Oral N OAEL = 5.0 mg/kg/day DAF = 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 food efficiency. Inhalation Short Term (1
- 30 days) Intermediate Term (1
- 6 months) Inhalation N OAEL

= 0.01 0 mg/L/day f Handler = 16.7 L/min HEC Handler = 0.0013 1 mg/L HEC Bystander = 0.0002 3 mg/L HED Handler = UF A = 3 x

UF H = 10x FQPA = 1 x Residential LOC

for MOE = 3 0 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 olfactory atrophy/necrosis in nasal tissue.Page **17** of **46**

**Table 4.3. 3**  **.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** 0.0 38 mg/kg/day
Cancer (oral, dermal, and inhalation) Classification: “Not L ikely 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 adjus ted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable. DAF = Dermal Absorption Factor. HEC = Human Equivalent Concentration. HED = Human Equivalent Dose. f = Respiratory frequency **T able 4.3.**  **3 .**  **2 :**  **Summary of Toxicological Doses and Endpoints for use in Occupational Human Health 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 DAF = 14% UF A = 10x

UF H = 10x FQPA = 1 x Occupation al

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 food efficiency. Inhalation Short Term (1
- 30 days) Intermediate Term (1
- 6 months) Inhalation N OAEL

= 0.01 0 mg/L/day HEC = 0.000 98 m/L/day f Applicators = 8.3 L/min HED Applicators = 0.05 6 mg/kg/day f Handlers = 16.7 L/min HED Handlers = 0.11 3 mg/kg/day f Handheld Spray = 29 L/min HED Handheld Spray = 0.19 5 mg/kg/day UF A = 3 x

UF H = 10x FQPA = 1 x Occupation al

LOC for MOE = 3 0 Inhalation Toxicity

– Rat

LOAEL = 0.03 mg/L/day based on duodenum mucosal hyperplasia and respiratory system findings including alveolar histiocytosis and olfactory atrophy/necrosis in nasal tissue.

Cancer (oral) Classification: “Not L ikely 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. DAF = Dermal Absorption Factor. HEC = Human Equivalent Concentration. HED = Human Equivalent Dose. f = Respiratory frequencyPage **18** of **46**

**5.0 Dietary Exposure and Risk Assessment**  **5.1 Residues of Concern Summary and Rationale**  The residues of concern for dietary risk assessment and the tolerance expression are summarized in Table 5.1 (MARC, D2780 44, L . Cheng, 10/9/20 01). HED has concluded that the residues of concern in plants includ e py raclostrobin and its desmethoxy metabolite (BF 500
- 3) for purposes of tolerance enforcement and risk assessment. For livestock commodities, HED has determined th at 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
-pyrazol
- 3
- ol (BF 500
- 5) and 1
- (4
- chloro
- 2
- hydroxy phenyl )
- 1 H

-py razol
- 3
- ol (BF 500
- 8). For drinking water, the residue of concern for p yr aclostrobin is the parent only
. **Table 5.1. Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance**  **Expression. Matrix**  **Residues included in Risk Assessment**  **Residues included in Tolerance**  **Expression** Plants Primary Crop Py raclostrobin , BF 500
- 3 Py raclostrobin , BF 500
- 3 Rotational Crop Py raclostrobin , BF 500
- 3 Py raclostrobin , BF 500
- 3 Livestock Ruminant Py raclostrobin , BF 500
- 5, BF 500
- 8 Py raclostrobin , BF 500
- 5, BF 500
- 8 Poultry Py

raclostrobin , BF 500
- 5, BF 500
- 8 Py raclostrobin , BF 500
- 5, BF 500
- 8 Drinking Water Py raclostrobin only Not Applicable **5 .2**  **Food Residue**  **Profile** IR
- 4 submitted field trial data on basil (MRID 47014803), chives (MRID 47014802), and dill (MRID 47014801). All studies were conducted at a seasonal rate of 0.80 lb ai/acre (2 applications at 0.40 lb ai/acre) with a 0
- day PHI. The proposed use pattern is 0.30 lb ai/acre (2 applications at 0.15 lb ai/acre) with a 0
- day PHI. The trials were at a 2.7X exaggerated rate, for each application and for the seasonal application. Proportionality w as used to adjust the experimental data to the 1X rate. The number of trials and geographic distribution are acceptable. The anal ytical method used is adequate for determination of the residue s of concern, and the samples were stored frozen for intervals supported by the storage stability

results. A summary of the resi due data from the crop field trials is presented in Appendix F , Table F .1. The existing field trial data for the crop group conversions are adequate. Processed Food and Feed Basil from each of the four field trials was dried. The median processing facto r (combined residues of p yr aclostrobin and BF 500
- 3) is 6.2X. These studies are adequate to estimate a processing factor for the combined residue of p yr aclostrobin and BF 500
- 3. In each of the trials, the fresh basil contained quantifiable residues of parent and metabolite.Page **19** of **46**

Livestock There are no feed items associated with dill seed or herbs from the herb subgroup 19A
. Therefore, the previous livestock dietary intake calculations and resulting tolerance recommendations are not changed. Rotational Crops Adequate limited field rotational crop studies are available supporting the existing tolerances for indirect residues in rotational crops. These data support the label
- specific plant
-back interval of 14 days for crops without py raclostrobin uses. No additional rotational crop data are required for purposes of this petition. **5.3 Water Residue Profile**  The new uses on herbs and dill seed were considered b y EFED, and no change from the 2013 values was considered necessary (D417303, E. Seifu, 07/10/2014). The drinking water residues used in the dietary

risk assessment were provided by EFED (D403871, D405066, F. Khan, 02/13/2013, Addendum 04/04/2013 ) and incorporated directl y into the dietary assessment. Water residues were incorporated in the DEEM
- FCID into the food categories “water, direct, all sources” and “water, indirect, all sources.” EDWCs were generated using EFED’s standard suite of models including the Pesticide Root Zone Model for Groundwater (PRZM
- GW, version 1.0, August 31, 20 12) and the Surface Water Calculator. 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 p yr aclostrobin for turf uses (D389729 , 09/06/2007 )
. 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 previously recommended for turf use
. The turf use is the same evaluation provided previously by EFED and originall y used in a 2007 assessment (D389729, 9/6/2007). All proposed new uses were considered. Table 5.3 provides a summary of the estimated concentrations of py raclostrobin in surf

ace and ground 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 water 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 0.02 0.02Page **20** of **46** 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 groundwater concentrations for acute was 0.02 μg/L 2007, D 389729
. 2 EDWCs are based on the 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 , 100% crop treated, and empirical or default process ing factors. Experimentally derived processing factors were used for fruit juices, tomato, sugarcane, and wheat commodities . For all other processed commodities, DEEM default processing factors were assumed. The estimated acute drinking water concentration for p yr aclostrobin (0.0356 ppm) was calculated based on a turf scenario for surface water and included in the dietary exposure assessment . A refined chronic dietary anal ys is was conducted for this assessm ent in order to compensate for exposure resulting from residential uses in the aggregate assessment. The chronic dietary anal ys is included tolerance
- level or average field trial residues, average percent crop treated estimate s (2014) when available , and empirical processing factors. Screening level percent crop estimates of agricultural uses of p yraclostrobin were provided previousl y by the Biological & Economic Anal ys is Division (BEAD). Experimentally derived processing factors were used for fruit juice s, tomato, sugarcane, 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 raclostrobin is classified as “not 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). 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 <2. 5%; blueberries 45%; broccoli 5%; cabbage 10%; caneberries 50%; cantaloupes 15%; carrots 35%; cauliflower <2.5%; celery <2.5%; cherries 50%; corn 10%; cotton <2.5%; cotton (seed treatment) 10%; cucumber 10%; dry beans/peas 10%; garlic 10%; grapefruit 30%; grapes 30%; hazelnuts (filberts) 20%; lemons <2.5%; lettuce 5%; nectarines 10%; onions 25%; oranges 5%; peaches 20%; peanuts 25%; pears 15%; green peas 5%; pecans <2.5%; peppers 10%; pistachios 30%; plums/prunes 5%; potatoes 20%; pumpkins 20%; rice <1%; so ybeans 5%; soybeans (seed treatment) 5%; spinach 5%; squash 15%; strawberries 65%; sugar beets 45%; sugarcane 10%; sweet corn 5%; tangelos 15%;Page **21** of **46**

tangerines 10%; tomatoes 25%; walnuts <1%; watermelons 30%; wheat 5%; wheat (seed treatment) <1%. Note that the sugarcane estimate is from a time limited Section 18 (exp 12/2014) and not the Section 3 registration (2013). Therefore, 100% crop treated was used for sugarcane. **5.4.3 Acute Dietary Risk Assessment**  The results of the acute dietary anal ys is for food an d drinking water indicate that acute dietary risks do not exceed the Agency ’s level 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). A separate assessment was conducted for females 13
- 49 years to address the developmental toxicity concerns. The e stimated exposure is at the 95 th percentile of 8 7 % of the aPAD for this population
. **5.4.4 Chronic Dietary Risk Assessment**  **s** Py raclostrobin exposure from the existing uses and the proposed new uses on dill seed and the herbs of crop subgroup 19A results in estimated risk s that are below the Agency ’s level of concern for food plus drinking water. The highest exposure and risk estimates for food plus drinking water utilized 8.1 % of the chronic population adjusted dose (cPAD) for the U.S. population and 2 7 % for children 1 to 2 ye ar s old, the mo st highl y exposed population subgroup. **5.4. 5**  **Summary Table**
**Table 5.4.5**  **. Summary of Dietary Exposure and Risk for Pyraclostrobin Food & Drinking Water.**

Population Subgroup Ac ute Dietary (95th Percentile) Chronic Dietary Dietary Exposure (mg/kg/day) % aPAD Dietary Exposure (mg/kg/day) % cPAD General U.S. Population 0.04687 1.5 0.002742 8.1 All Infants (< 1 year old) 0.061725 2.1 0.004082 12 Children 1
- 2 years old 0.083114 2.8 **0.009231 27**  Children 3
- 5 years old 0.074744 2.5 0.006258 18 Children 6
- 12 years old 0.044276 1.5 0.003566 11 Youth 13
- 19 years old 0.031310 1.0 0.001869 5.5 Adults 20
- 49 years old 0.041809 1.4 0.002269 6.7 Adults 50
- 99 years old 0.041843 1.4 0.002282 6.7 Females 13
- 49 years old **0.043510 87**  0.002049 6.0 *The subpopulations with the highest risk estimates are bolded.Page **22** of **46**

**6.0 Residential (Non**  **- Occupational) Exposure/Risk Characterization**  There are no residential uses proposed for py raclostrobin with this action. However, there are existing residential uses on turf , ornamentals and garden landscapes, and on residential fruit and nut trees. Residential exposure is expected to be short
- term only
. These existing residential uses were assessed in the last HED exposure and risk assessment (D40506 5 , B. O’Keefe, 07/03/201 3) and the occupational and residential exposure risk assessment (D403449 , C. Walls, 04/30/20 13 ) to reflect updates to HED’s 2012 Residential SOPs 2 along with policy changes for body

weight assumptions
. All registered products do not lead to any residenti al handler or residential post application risk estimates of concern. All residential handler dermal and inhalation exposure risk estimates were not of concern to HED, with margins of exposure (MOEs) ranging from 590 to 3,9 00,000 (LOCs <100). The only new residential exposure assessment conducted in this current assessment was for handler inhalation exposure from a pplying WDG formulation to turf via manually pressurized handwand or backpack sprayer using the results from the new inhalation toxicity study and using HEDs/HECs. This was from the previous highest exposure risk estimate MOE of 590, and using the HED/HEC method resulted in an MOE of 97 (LOC <30), which is still not of concern . All previ ously assessed residential post
- application dermal and incidental oral exposure risk estimates were also not of concern to HED, with MOEs ranging from 150 to 34 0,000. Inorder to incorporate residential exposure into the short
- term aggregate risk assessment, a summary of the scenarios that were previously determined to be most protective are presented in Table 6.1
. Note that inhalation exposure risk estimates to adults are not aggregated, since these are portal of entry effects. **Table 6.1. Summary of Re sidential Exposures Used in the Pyraclostrobin Short**  **- term Aggregate Assessments.**  **Lifestage Route of Exposure**  **Scenario Dose**  **(m g/k** **g/day) MOE**  Adult 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. 1**  **Residential Bystander Post**  **- application**  **Inhalation Exposure** Volatilization of pesticides may be a source of post
- application inhalation exposure to individuals nearb y pesticide applications. The agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory

Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipol y/ SAP/meetings/2009/120109meeting.html). The agency has evaluated the SAP report and has develope d a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA
- HQ
- OPP
- 2014
- 0219).
2 Available: http://www.epa.gov/pesticides/science/residential
- exposure - sop.htmlPage **23** of **46**

During Registration Review, the agency will utilize this analysis to determine if data (i.e., flux studies, route
- specific inhalation toxicological studies) or further analysis is required for py raclostrobin. **6. 2**  **Spray Drift** Spray drift is a potential source of exposure to those nearby pesticide applications. This is particularl y the case with aerial application, but, to a lesser extent, spray drift can also be a potential source of exposure from the ground application methods (e.g., groundboom and airblast) emplo yed for pyraclostrobin. The agency has been working with the Spray Drift Task Force (a ta sk force composed of various registrants which was developed as a result of a Data Call
- Inissued by

EPA), EPA Regional Offices and State L ead Agencies for pesticide regulation and other parties to develop the best spray drift management practices (see the agency ’s Spray Drift website for more information). 3 The agency has also developed a policy on how to appropriatel y consider spray drift as a potential source of exposure in risk assessments for pesticides. The potential for spray drift will be quantit atively evaluated for each pesticide during the Registration Review process which ensures that all uses for that pesticide will be considered concurrently . The approach is outlined in the revised (2012) Standard Operating Procedures For Residential Risk A ssessment (SOPs)

- Residential Exposure Assessment Standard Operating Procedures Addenda 1: Consideration of Spray Drift. This document outlines the quantification of indirect non
- occupational exposure to drift. **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 comp ared 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
. A separate assessment was conducted for females 13
- 49 years to address the developmental toxicity concerns. The estimated exposure is at the 95 th percentile of 8 7 % of the aPAD for this populati on.

3 Available: http ://www.epa.gov/opp00001/factsheets/spraydrift.htmPage **24** of **46**

**7.2 Short** **- Term Aggregate Risk**  There is potential short
- term exposure to py raclostrobin via dietary

(which is considered background exposure) and residential (which is considered primary) exposure pathways. For adults, these pathways lead to exposure v ia oral (background) as well as dermal and inhalation (primary) routes. For pyraclostrobin only oral and dermal exposures can be aggregated. The most conservative scenarios were chosen for each population (e.g., hand
- to - mouth exposure from treated turf f

or children 1
- 2 years old). For a description of the residential exposure scenarios considered in the aggregate assessment, see Section 6. 0
. The greatest exposure non
- cancer aggregate MOE for adults is 230 and is not of concern to HED. The aggregate M OE for children 1
- 2 years old, including incidental oral exposures from treated turf, is 1 1 0 and is not of concern to HED. **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 0.03 3 1 5 0 5.8 0.0048 0.009231 400 110 Child 6
- 11 yrs 5 0.01 490 5 NA 0.003566 1, 6 00 3 8 0 Youth 11
- 16 yrs 5 0.0015 3,300 5 NA 0.001869 3,1 00 1, 6 00 Adult Post
- application 5 0.019 260 5 NA 0.002742 2,1 00 230 1 The Level of Concern MOE is 100. 2 Total Combined MOE = 1/ [(1/MOE Dermal ) + (1/MOE Oral )] **7.3 Chronic Aggregate Risk**  Chronic exposure from the residential pathway is not anticipated based on the current py raclostrobin 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 0.0 0 2 7 42 mg/kg/day for the general U.S. population ( 8.1 % of the cPAD) and 0. 0 09231 mg/kg/day ( 2 7 % of the cPAD) for children 1 to 2 ye ar s old, the population subgroup with the highest estimated chronic dietary exposure to py

raclostrobin . 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 b ased on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to py raclostrobin and any other substances and py raclostrobin does not appear to produce a toxic metabolite produced b y other substances. For the purposes o f this tolerance action, therefore, EPA has not assumed that py raclostrobin 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 commonPage **25** of **46**

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/. **9.0 Occupational Exposure/Risk Characterization**  Py raclostrobin is proposed for new uses on dill seed and herb subgroup 19A. Application methods, maximum application rates, and use sites are summarized in S ection 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 raclostrobin during handling (mixing, loading, and appl ying) and post - application activities. Py raclostrobin us e is propos ed for up to two applications, with a minimum retreatment interval of 7 days. Additionally , for both dermal and inhalation exposures the same endpoint and point of departure were selected for short
- and intermediate
- term durations, and therefore, short
- term exposure and risk estimates are considered to be protective of intermediate
- term exposure and risk estimates
. **9.1 Short** **- /Intermediate**  **- Term Handler Risk**  HED uses the term handlers to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct job functions or tasks related to 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, 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 b y the uncertainty factors that are applied to the assessment. HED applies a 10X fa ctor 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 py raclostrobin occupational dermal exposure assessment is 100X. Occupational dermal exposure and risk resulting in MOEs greater than or equal to 100 will not be of concern to HED. For inhalation exposures, the LOC is 30 , which includes interspecies (3 X), and intraspecies (10 X) uncertainty factors. The interspecies factor was reduced from 10 X to 3 X due to the HEC calculation accounting for pharmacokinetic interspecies differences , but the intraspecies factor is retained at 10 X because HEC calculation does not account for pharmacody namic intraspecies differences. Summaries of the short
- and intermediate
- term risk estimate s for occupational handlers appl ying py raclostrobin are provided in Appendix E , Table s E
. 1 and E .2
. The dermal MOEs range from 63 (mixing/loading/applying of WG formulation to support mechanically pressurized handgun applications) to 2, 6 00 ( ground application to herbs) at baseline PPE. When assessed at labelled PPE (e.g., including gloves), the dermal MOE of 63 (mixing/loading/applying of WG formulation to support mechanically pressurized handgun applications) increas ed to 210. Since all dermal MOEs at labelled PPE are greater than the LOC of 100, they are not a concern to HED.Page **26** of **46**

The inhalation MOEs range from 34 (mixing/loading of WG formulation to support ground applications to dill seed) to 1 ,1 00 ( ground applicati on to herbs) at baseline PPE (no respirator). A ll handler scenario MOEs at labelled PPE (e.g., no respirator) are greater than the LOC of 30 , which are not a concern to HED. **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 area s to perform job functions, including activities related to crop production, such as scouting for pests or harvesting. Post
- application exposure levels vary over time and depend on such things as the ty pe of activity , the nature of the crop or target that was treated, the ty pe of pesticide application, and the chemical’s degradation 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 P**  **ost -** **Application Risk**  Based on the proposed use patterns, short
- and intermediate
- term post - application dermal exposures to workers re
- entering treated areas is possible. All post
- application scenarios resulted in MOEs greater than 100 on day 0 (12 hours after application) and therefore are not of concern to HED . The MOEs for py raclostrobin ranged from 380 to 10 ,000. DFR studies are not re quired at this time for py

raclostrobin since all occupational dermal MOE s are ≥ 38 0 and are greater than 2 times the LOC based on default input values. The short
- and intermediate
- term non - cancer post - application risk estimates for workers are provided in Appendix E , Table E
. 3
. 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 eye and skin irritation potential. Short
- and intermediate
- term post - application risk estimates were not a concern on day

0 (12 hours following application) for all post
- application activities. Under 40 CFR § 156.208 (c) (2) (iii), active ingredient s classified as toxicity category III or IV for acute dermal, eye irritation and primary skin irrit ation are assigned a 12
- hour REI. Therefore, the [1 56 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** There are multiple potential sources of post
- applicati on inhalation exposure to individuals performing post
- application activities in previously treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides. The agency

sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 (http://www.epa. gov/scipoly /SAP/meetings/2009/120109meeting.html ). The agency hasPage **27** of **46**

evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA
- HQ
OPP
- 2014
- 0219 ). During Registration Review, the agency will utilize this anal ys is to determine if data (i.e., flux studies, route
- specific inhalation toxicological studies) or further anal ys is is required for py

raclostrobin
. In addition, the Agency

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

the need for and, subsequently , the way to incorporate occupational post
- application inhalation exposure into the agency's risk assessments. Although a 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.Page **28** of **46**

**10.0 References**  S. Funk, 0 6 / 30 /20 1 4 , D4 2115 4
. Py raclostrobin: Petition for the Establishment of Permanent Tolerances and Registration for Use on Herb Subgroup 19A and Dill. Request for Crop Group Expansions/Revisions for Stone Fruit Group 12
- 12 and Tree Nut Group 14
- 12. Summary of Analy tical Chemistry

and Residue Data
. S. Funk, 0 7 / 1 7 /20 1 4 , D4 211 48
. Py raclostrobin. Acute and Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessments to Support New Uses on Dill Seed and Herbs Subgroup 19A. C. Walls, 12 / 1 5 /20 14 , D4211 49
. Py raclostrobin . Occupational and Residential Exposure Assessment for proposed new uses on dill seed and the herb subgroup 19A. C. Walls, 0 4/30/20 13, D 403 449
. Py raclostrobin . Occupational and Residential Exposure Assessment for proposed new uses of py raclostrobin 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, 04/04/2013, D403871. Addendum of Drinking Water Exposure Assessment for the Section 3 New Uses of Pyrac lostrobin on Various Agricultural Crops and Residential Ornamentals. E. Seifu, 07/10/2014, D417303. Ecological Risk and Drinking Water Assessment Conclusions for Py raclostrobin IR
- 4 Proposed New Use on Herb Subgroup 19A and Dill.Page **29** of **46**

**A ppendix**  **A .**  **Toxicolo gy Profile and Executive Summaries**  **A.1 Toxicology Data Requirements**  The requirements (40 CFR 158.500) for food uses of py raclostrobin are in the table below. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were use d. **Table A .1**  **: Toxicology Data Requirements of Pyraclostrobin.**  **Study Technical**  **Required Satisfied**  870.1100 Acute Oral Toxicity
................................ ....................... 870.1200 Acute Dermal Toxicity
................................ .................. 870.1300 Acute Inhalation Toxicity
................................ .............. 870.2400 Primary Eye Irritation
................................ .................... 870.2500 Primary Dermal Irritation
................................ .............. 870.2600 Dermal Sensitization
................................ ...................... yes yes yes yes yes yes yes

yes yes yes yes yes 870.3100 Oral Subchronic (rodent)
................................ ............... 870.3150 Oral Subchronic (nonrodent)
................................ ......... 870.3200 21
- Day

Dermal
................................ .............................. 870.3250 90
- Day

Dermal
................................ .............................. 870.3465 90
- Day

Inhalation
................................ .......................... yes yes yes no CR yes

yes yes no yes 870.3700a Developmental Toxicity (rodent)
................................ ... 870.3700b Developmental Toxicity (nonrodent)
............................. 870.3800 Reproduction
................................ ................................ . yes yes yes yes

yes yes 870.4100a Chronic Toxicity (rodent)
................................ .............. 870.4100b Chronic Toxicity (nonrodent)
................................ ........ 870.4200a Oncogenicity (rat)
................................ .......................... 870.4200b Oncogenicity (mouse)
................................ .................... yes yes yes yes yes

yes yes yes 870.5100 Mutagenicity

—Gene Mutation
- bacterial
..................... 870.5300 Mutagenicity

—Gene Mutation
- mammalian
................ 870. 5375 Mutagenicity

— Structural Chromosomal Aberrations
... 870. 5550 Mutagenicity

—Other Genotoxic Effects
....................... yes yes yes yes yes

yes yes yes 870.6100a Acute Delayed Neurotoxicity (hen)
............................... 870.6100b 90
- Day

Neurotoxicity (hen)
................................ ........... 870.6200a Acute Neurotoxicity Screening Battery (rat)
................. 870.6200b 90
- Day

Neurotoxicity Screening Battery (rat)
............... 870.6300 Develop. Neurotoxicity
................................ ................. CR CR yes yes CR NA

NA yes yes NA 870.7485 General Metabolism
................................ ...................... 870.7600 Dermal Penetration
................................ ........................ 870.7800 Immunotoxicity
................................ ............................. yes CR yes yes

NA yes CR Conditionally Required NA Not Applicable 1 Either guideline study type may be used to satisfy the data requirement (e.g., 870.5300 or 870.5375)Page **30** of **46**

**A.2 Toxicity Profile**  **s Table A.2.1. Acute Toxicity of**  **Pyraclostro b**  **in 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
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 Pyraclostrobin**  **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 (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 (males), changes in clinical chemistry (increased urea and decreased triglycerides), and increased incidences in females of lymph node apoptosis, thymus atrophy, and ulcer/erosion in the glandular stomach.Page **31** of **46**

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

Inhalation Toxicity (Rat) 46638801 (2005)

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

uideline NOAEL (mg/L/day) : M = 0.001 F = 0.001 LOAEL (mg/L/day) : 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. 4
- Week Inhalation Toxicity (Rat) 49459611 (2014)

Applied Dose (mg/L/day) : M: 0 , 0.0 3 0 , 0.0 10 , 0.0 30 F: 0 , 0.0 3 0 , 0.0 10 , 0.0 30 Acceptable / G

uideline NOAEL (mg/L/day) : M = 0.0 10 F = 0.0 10 LOAEL (mg/L/day) : M = 0.0 30 F = 0.0 3 0 Based on increased incidence of olfactory epithelium atrophy/necrosis in the nasal cavities of both sexes.
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 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 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.Page **32** of **46**

**Table A.2. 2**  **. Subchronic, Chronic, and**  **Other Toxicity Profiles Guideline**  **Study Type MRID (year) / Doses / Classification**  **Results** 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
. 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). 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
.Page **33** of **46**

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

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.

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 precip i tating 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 after 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 synthesis, 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.Page **34** of **46**

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

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). 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, a

nd 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 th e 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 hydro xylations, and cleavage of the ether bond with subsequent oxidation; these reactions were followed by phase II glucuronidation and sulf ation.Page **35** of **46**

**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 (a.k.a., dermal absorption factor (DAF)) 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 p orous band age. This material must be considered unavailable for absorption. 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 fo r 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 radioactivity 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 incre ased by 21.6x compared to the 25.2x increase in the dose level. This 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 48830602 (2012) Dietary Concentration (ppm): 0, 50 , 20 0 , 750 Intake Dose (mg/kg/day): F: 0, 13 , 50 , 202 48830603 (2012) Dietary Concentration (ppm): 0, 50 , 20 0 , 750 Intake Dose (mg/kg/day): F: 0, 14 , 55 , 1 91 Acceptable / Guideline Immunotoxicity NOAEL (mg/kg/day): M = NA F = 165 LOAEL (mg/kg/day): M = NA F > 165 Systemic NOAEL (mg/kg/day): M = NA F = 50 LOAEL (mg/kg/day): M = NA F = 165 Based on decreased body weight, spleen weight, and thymus weight
.Page **36** of **46**

**Appendix B**  **. Methodologies for Human**  **- Equivalent Concentration (HEC) Calculations**  **. B.1**  **Executive Summary: 4 -**  **week Inhalation Toxicity in Rats (MRID 49459611)** In an inhalation toxicity

study (MRID 49459611), py

raclostrobin (99 .02% a.i., batch number: COD
- 001236) was administered to Crl:WI (HAN) rats (10/sex/dose) nose
- only via aerosol at dose levels 0, 3, 10, or 30 mg/m 3 /day (0, 0.003, 0.010, or 0.030 mg/L/day) for 6 hours/day on 20 work days during a 28
- day period. Additionally , a recovery group composed of Crl:WI (HAN) rats (10/sex/dose) were dosed at 0 or 30 mg/m 3 /day (0 or 0.030 mg/L/day) for the same duration as the main group but were given a 4
- week post
- exposure recovery period prior to necrops y. There were no unscheduled mortalities in any treatment group. In the treated animals, there were no test substance
- related effects or findings with respect to clinical signs of toxicity, body weight, food consumption, ophthalmoscopic findings, hematology , clinical chemistry , organ weights, and macroscopic pathology
. At the 30 mg/m 3 /day

dose of the main group, the test substance
- related finding was increased incidences of olfactory

epithelium atrophy

/necrosis (nasal cavity levels II
- IV) in both sexes. The NOAEL is 10 mg/m 3 /day (0.010 mg/L/day) and the LOAEL is 30 mg/m 3 /day (0.030 mg/L/day) based on the increased incidence of olfactory epithelium atrophy

/necrosis in the nasal cavities of both sexes. This study

is classified as Acceptable/ Non
- Guideline and satisfies the guideline requirement for a 90
- day inhalation toxicity study ( OCSPP 870.3465). **B. 2**  **Reference Concentration (RfC) Background**  The RfC methodology

applies a dosimetric adjustment that takes into consideration not only the differences in minute ventilation rate (VE ) but also the physicochemical properties of the inhaled compound, the ty

pe of toxicity

observed (e.g., s ys temic vs. portal of entry) and the pharmacokinetic (PK) but not pharmacodynamic (PD) differences between animals (A) and humans (H). Based on the EPA’s RfC guidance (1994), the methodology for RfCs derivations is an estimate of the quantitative dose
- response assessment of chronic non
- cancer toxicity for individual inhaled chemicals and includes dosimetric adjustment to account for the species
specific relationships of exposure concentration to deposited/delivered dose. This adjustment is influenced b y the phys icochemical properties of the inhaled compound as well as the ty pe of toxicity observed (e.g., systemic vs. portal o f entry), and takes into consideration the PK differences between animals and humans. To provide greater accuracy , the RfC also takes into account the effect of aerosols and gases on the extrathoracic (ET), tracheobronchial (TB), and pulmonary

(PU) respir atory

regions (r) as described in the figure below.Page **37** of **46**

**Figure B.**  **2 .1**  **:** Regions of the human respiratory tract used for HEC calculations (Figure 3
- 1 of the 1994 RfC methodology document) Though the RfC methodology was developed to estimate toxicity of inhal ed chemicals over a lifetime, it can be used for other inhalation exposures (e.g., acute, short
- term, and intermediate
term exposures) since the dosimetric adjustment incorporates mechanistic determinants of disposition that can be applied to shorter durat ions of exposure s provided the assumptions underlying the methodology are still valid. These assumptions, in turn, vary depending on the ty pe of toxicity

observed. Thus, the derivation of a Human Equivalent Concentration (HEC) for inhaled chemicals is de scribed by the following equation: HEC r = E × (D A ÷ D H) × (W A ÷ W H) × DAF r HEC: Human equivalent concentration (mg/L) E : Experimental exposure level (mg/L) or P oint of Departure (POD) D: Number of hours exposed per 24 hours W: Number of days exposed per 7 days DAF: Dosimetric adjustment factor is a multiplicative factor used to adjust an observed inhalation exposure concentration of an animal (A) to the predicted inhalation exposure concentration for a human (H) that wo uld be associated with the same dose delivered to a specific respiratory region (r) or target tissue
. A: Test animals H: Humans HECs can be determined using inhalation studies that are conducted using either aerosols or gases. However, aerosols are assumed to be spherical, relatively insoluble, and non - hygroscopic particles in accordance with the 1994 RfC methodology and thus ph ys ically distinct from gases. Therefore, the DAF for aerosols are determined differently from gases.Page **38** of **46**

For inhalation studies using aerosols, the DAF is referre d to as the regional deposited dose ratio (RDDR) and it is the ratio between the estimated regional deposited doses (RDD) in test animals (A) and humans (H). The RDDR is determined through characterizing particulate exposure by defining the particulate diameter (mass median aerody namic diameter [MMAD]) and the geometric standard deviation (σ g) ; MMAD and GSD are used to describe the particle size distribution of any

aerosol statistically

based on the weight and size of the particles . The RDDR is generall y described b y the following equation: RDDR

r = (RDD r,A ÷ RDD r,H) × (NF H ÷ NF A) = ((10 - 6 × C i,A × VE,A × F r,A) ÷ (10 - 6 × C i,H × VE,H × F r,H)) × (NF H ÷ NF A) = (C i,A ÷ C i,H) × (VE,A ÷ VE,H) × (F r,A ÷ F r,H) × (NF H ÷ NF A) C i : Inhaled c oncentration (mg/c m 3 = 10 - 6 mg/m 3 ) V E : Minute volume (mL/min) F: Fractional deposition NF: Normalizing factor However, the RDDR can be refined b y appl ying the appropriate normalizing factor (NF) based on effects observed in the inhalation study . The normalizing factor for resp iratory (i.e., portal of entry) effects is the surface area (SA) of the specific respiratory region, but for extrarespiratory (i.e., systemic) effects it is the animal’s body weight (BW). The refined RDDR is described by the following equations: Respiratory

Effects RDDR

r = (C i,A ÷ C i,H) × (VE,A ÷ VE,H) × (F r,A ÷ F r,H) × (SAr,H ÷ SAr,A) Extrarespiratory

Effects RDDRER = (C i,A ÷ C i,H) × (VE,A ÷ VE,H) × (F TOT,A ÷ F TOT,H) × (BW H ÷ BWA) TO T: Total respiratory tract For inhalation studies using gases, the DAF is referred to as the regional gas dose ratio (RGDR) and it is the ratio between the estimated regional gas doses (RGD) in test animals (A) and humans (H). The RGDR is determined through characterizing exposure b y concentration, temperature, pressure, and gas category (i.e., Categories 1, 2 and 3). Category 1 gases are defined as gases that are highl y water- soluble and/or rapidly irreversibl y reactive in the respiratory tract; this category

of gas does not significantl y accumulate in the blood and thus h as potential for respiratory

but not extrarespiratory

toxicity . Category

2 gases are defined as gases that are moderatel y water- soluble that may be rapidl y reversibly

reactive or moderately

to slowly irreversibl y reactive in the respiratory tract; this category

of gas has the potential for significant accumulation in the blood and thus has the potential for both respiratory and extrarespiratory toxicity . Category

3 gases are defined as gases that are relativel y water insoluble and unreactive in the ET and TB regions; this category of gas has the potential for extrarespiratory but not respiratory

toxicity
. Reactivity

is defined to include both the propensity for dissociation as well as the ability

to serve as substrate for metabolism in the respiratory tract. The RGDR for different gas categories and respiratory regions are described in the EPA’s 1994 document:Page **39** of **46**

“Methods for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry .” After the appropriate DAF has been applied to calculate the HEC, a route
- to - route extrapolation is conducted to convert HEC inhalation units (mg/L) into human equivalent dose (HED) units (mg/kg/day). The HED generated provide unique doses for different inhalation exposure scenarios. The route - to - route extrapolation is described with the following equation: HED r = HEC r × A × CF × D H × AF HED: Human equivalent dose (mg/kg/day) HEC: Human equivalent concentration (mg/L) A: Absorption ratio through the respiratory tract as compared to the oral route; assumed to be unity CF: Human
- specific value (L/hr/kg) that accounts for volume respired per unit time. CF equals 11.8 L/hr/kg based on the default breathing rate assumed for a typical human in the HEC calculation (i.e., the RfC Methodology’s default breathing rate for HEC is 13.8 L/min for a 70 kg human; CF = 13.8 L/min ÷ 70 kg = 11.8 L/hr/kg) D: Number of hours exposed per 24 hours for humans AF: Relative ratio that accounts for relative changes in respiratory rate due to activity level. Different AF values should be u s ed for different occupational and residential scenarios **B. 3**  **HEC Calculations for Short -**  **and Intermediate -**  **Term Inhalation**  **Exposure Scenarios** Since py raclostrobin is an aerosol, the HEC was determined using a RDDR for the DAF. In turn, the RDDR for this chemical in Table B.2.1 was determined by appl ying the methodology above to information extracted from the p yraclostrobin subchronic inhalation toxicity study (MRID 49459611 ). **Table B.2.1 Regional Deposited Dose Ratio (RDDR) [MMAD = 1.6**   **m;**  **g = 4.0]**  **Species Body Weight** 

**(BW, g) Minute Ventilation** 

**(V E**  **, m L)**  **Extrathoracic (ET)**

**Surface Area (SA, cm 2**  **) Fractional Deposition (F)**  Rat (R) 1 9 8 14 8
. 5 15 0.3 47 Human 70000 13800 200 0.3 81 Ratio 0.003 0.01 1 0.075 0.9 10 RDDR NA NA 0. 1 31 The magnitude of the uncertainty factors (UF) applied is dependent on the methodology used to determine the risk estimates. The RfC methodology takes into consideration the PK differences, but not the PD difference. Consequently , the UF for interspecies extrapolation may be reduced to 3 x (to account for the PD differences) while the UF for intraspecies variation is retained at 10 x . Thus, the UF when using the RfC methodology is 30 x . **B. 4**  **HEC & HED**  **Calculations for Occupational and Residential**  **Inhalation Exposure**  **Scenarios** HECs are calculated using DAFs, and DAFs are chosen based on the inhalation ty pe and respiratory

surfaces affected. For py raclostrobin, the RDDRET was chosen as the DAF because the subchronic inhalation toxicity study delivered the chemical via aerosol and the extrathoracic respiratory

surface was protective of both the respiratory toxicity (i.e., olfactory

atrophy and necrosis) and s ys temic toxicity (i.e., mucosal hy

perplasia in the duodenum). Table B.3.1Page **40** of **46**

contains HECs for potential o ccupational and residential scenarios; residential bystander exposure was assumed to be 24 hours/day and 7 days/week. The HECs in the table were generated using the following equation: HEC ET = E × (D A ÷ D H ) × (WA ÷ W H) × RDDRET HEC: Human equivalent concentration (mg/L) E : Experimental exposure level (mg/L) or P oint of Departure (POD) D: Number of hours exposed per 24 hours W: Number of days exposed per 7 days DAF: Dosimetric adjustment factor is a multiplicative factor used to adjust an observed inhalat ion exposure concentration of an animal (A) to the predicted inhalation exposure concentration for a human (H) that wo uld be associated with the same dose delivered to a specific respiratory region (r) or target tissue
. A: Test animals H: Humans **Table B.3.1 HEC Array for Occupational and Residential Risk Assessment**  **Exposure Study**  **POD / r D**  **A D**  **H W** **A W** **H RDDR**  **HEC UF**  Occupational Short and Intermediate Term Applicators Inhalation Toxicity

MRID 4 9459611 NOAEL = 0.01 0 mg/L

r = ET 6 8 5 5 0.1 31 0.0009 8 UF A = 3x UF H = 10x Handlers Handheld Spray Residential Short and Intermediate Term Handler Inhalation Toxicity

MRID 4 9459611 NOAEL = 0.01 0 mg/L

r = ET 6 2 5 N/A 0.1 31 0.0013 1 UF A = 3x UF H = 10x Bystander 24 7 0.0002 3 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 (mg/L)
. LOAEL = lowest observed adverse effect level (mg/L)
. r = target respiratory region. D A = Number of hours exposed per 24 hours for animals. D H = Num ber of hours exposed per 24 hours for humans. W A = Number of days exposed per 7 days for animals. W H = Number of days exposed per 7 days for humans. RDDR = Regional deposited dose ratio. HEC = Human Equivalent Concentration (mg/L). UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). N/A = not applicable. ET = Extrathoracic. TB = Tracheobronchial. PU = Pulmonary. HED’s route
- to - route extrapolation converts human and animal values from mg/L concentrations to mg/kg oral
- equivalent doses. The equation uses a single conversion factor to account for default body weights and respiratory volumes. An activity factor is used to account for increased exposure resulting from increased respiration. More information and details in: Memo, “Route
to - Route Extrapolations” J. Whalen and H. Pettigrew, 10/10/98. Table B.3.2 contains HEDs for potential occupational and residential scenarios; residential exposure was assumed to be 24 hours/day and 7 days/week. The HEDs in the table we re generated using the following equation: HED ET [mg/kg/day] = HEC ET [mg/L ] × A × CF [L/hr/kg] × D [hr/day] × AF A: Absorption ratio through the respiratory tract as compared to the oral route; assumed to be unity CF: Human
- specific value that accounts f or volume respired per unit time. CF equals 11.8 L/hr/kg based on the default breathing rate assumed for a typical human in the HEC calculation (i.e., the RfC Methodology’s default breathing rate for HEC is 13.8 L/min for a 70 kg human; CF = 13.8 L/min ÷ 7 0 kg = 11.8 L/hr/kg) D: Number of hours exposed per 24 hours AF: Relative ratio that accounts for relative changes in respiratory rate due to activity level. Different AF values should be suited for different occupational and residential scenariosPage **41** of **46**

**Table B.3.**  **2 HE**  **D Array for Occupational and Residential Risk Assessment**  **Exposure HEC**  **A CF**  **D H**  **AF HED**  **UF** Occupational Short and Intermediate Term Applicators 0.0009 8 1.0 11.8 8 0.6 0.05 6 UF A = 3x UF H = 10x Handlers 1.2 0.11 3 Handheld Spray 2.1 0.19 5 Residential Short and Intermediate Term Handler 0.0013 1 1.0 11.8 2 1.2 0.0 38 UF A = 3x UF H = 10x Bystander 0.0002 3 1.0 11.8 24 N/A N/A HEC = Human Equivalent Concentration (mg/L). HED = Human Equivalent Dose (mg/kg/day). A = Absorption ratio through the respiratory tract as compared to the oral route. CF = Human
- specific value that accounts for volume respired per unit time

. D H = Number of hours exposed per 24 hours for humans. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). N/A = not applicable. **Appendix C**  **. Physicochemical Properties of**  **Py raclostrobin**  **. TABLE B. Physicochemic**  **al 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.Page **42** of **46**

**Appendix D**  **. Review of Human Research**  The PHED Task Force, 1995. The Pesticide Handlers Exposure Database, Version 1.1. Electronic Database. Task Force Members: Health Canada, U.S. EPA, and the National Agricultural Chemicals Associations, released February 1995. The Agricultural Handler Exposure Task Force (AHETF) , 2011. The Occupational Handler Unit Exposure Surrogate Reference Table. U.S. EPA. Released June 21, 2011. Data from the Outdoor Residential Exposure Task Force (ORETF). HED Residential Standard Operating Procedures (2012).Page **43** of **46**

**Appendix E**  **. Occupational Handler and Post** **- application Exposure and Risk Estimates** 

**Table E**  **.1. Occupational Handler Non -**  **Cancer Dermal Exposure and Risk Estim ates for Pyraclostrobin.**  **Exposure Scenario Crop**  **Dermal Unit Exposure (μg/lb ai)**  **1 Ma** **x**

**Applic Rate 2**  **(lb ai/A) Area Treated** 

**or Amount Handled**  **Daily 3**  **Dermal**

**Baseline Dermal**  **Baseline + gloves Baseline**  **Baseline +**

**Gloves Dose**  **(m g/k** **g/day) 4**  **MOE 5** 

**(LOC=100) Dose** 

**(m g/k** **g/day) 6**  **MOE 7** 

**(LOC=100)** Mixer/Loader of WDG Groundboom application Herbs 227 NA 0.15 80 0.0055 910 NA NA Groundboom application Dill 227 NA 0.15 200 0.014 360 NA NA Applicator of Liquids Groundboom application Herbs 78.6 NA 0.15 80 0.0019 2,600 NA NA Groundboom application Dill 78.6 NA 0.15 200 0.0048 1,000 NA NA Mixer/Loader/Applicator of WDG Mechanically pressurized handgun Herbs

Dill 1300 390 0.030 lb ai/gal 1000

gal 0.079 **63** 0.024 210 NA: Not assessed 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).Page **44** of **46**

NA: Not assessed 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 Inhalation Dose = Inhalation 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). 5 Inhalation MOE = I

nhalation HED (mg/kg/day) ÷ I nhalation Dose (mg/kg/day). Where: Mixer /loader MOEs use HED (based on inhal rate 16.7 L/min) of 0. 11 3 mg/kg/day Gr oundboom applicators MOEs use HED (based on inhal rate 8.3 L/min) of 0.056 mg/kg/day **Table E**  **.2. Occupational Handler No n**  **- Cancer Inhalation Exposure and Risk Estim**  **ates for Pyraclostrobin. Exposure**  **Scenario Crop**  **Baseline Inhalation**  **Unit Exposure (μg/lb ai)**  **1 Max** 

**Applic Rate 2**  **(lb ai/A) Area Treated or** 

**Am ount Handled**  **Daily 3**  **Inhalation Baseline**  **(no respirator) Dose**  **(m g/kg/day)**  **4 MOE**  **5**

**(LOC=30)** Mixer/Loader of WDG Groundboom Herbs 8.96 0.15 80 0.0014 84 Groundboom Dill 8.96 0.15 200 0.0034 34 Applicator of Liquids Groundboom Herbs 0.34 0.15 80 0.000051 1,100 Groundboom Dill 0.34 0.15 200 0.00013 440 Mixer/Loader/Applicator of WDG Mechanically pressurized handgun Herbs

Dill 3.9 0.030 lb ai/gal 1000

gal 0.0015 130Page **45** of **46**

**Table E**  **.3 . Occupational Post**  **- application Non**  **- Cancer Exposure and Risk Estim**  **ates for Pyraclostrobin.**  **Crop/Site Activities**  **Transfer Coefficient (cm** **2 /hr)**  **DFR 1** 

**(μg/cm 2**  **) Dermal Dose** 

**(m g/k** **g/day) 2**  **MOE 3** 

Dill and Herbs Irrigation (Hand Set) 1,900 0.42 0.013 380 Scouting 1,100 0.0075 660 Hand weeding 70 0.00048 10,000 1 DFR = Application Rate × F × (1
- D) t × 4.54E8 μg/lb × 2.47E
- 8 acre/cm2 ; where F = 0.25 and D = 0.10 per day 2 Daily Dermal Dose = [DFR (μg/cm2 ) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption (14%)]  BW (69 kg). 3 MOE = POD (mg/kg/day) / Daily Dermal Dose. **Appendix F**  **. Summaries of Field Residue Data Table**  **F .1. Summary of Residue Data from Field Trials with Pyraclostrobin.**  Crop Matrix Total Applic.

Rate (lb ai/A) PHI

(days) Com

bined Residue Levels of Pyraclostrobin and its Metabolite BF 500
- 3 (ppm) 1
n Min. Max. HAFT Median (STMdR) Mean

(STMR) Std. Dev. BASIL. Proposed use pattern: Two foliar sprays at 0.15 lb ai/A/application for a seasonal rate of 0.3 lb ai/A with a 0
- day PHI
. Fresh Basil 0.80
- 0.83 0 8 7.2 21.1 16.1 8.9 10.9 4.5 3
- 4 8 1.3 7.5 7.4 4.9 4.8 2.6 Dried Basil 0 4 40.1 80.6 80.6 74.7 67.5 18.5 CHIVES
. Proposed use pattern: Two foliar sprays at 0.15 lb ai/A/application for a seasonal rate of 0.3 lb ai/A with a 0
- day PHI. Chives 0.81
- 0.83 0 8 0.7 8.8 7.8 6.9 5.8 3.1 DILL. Proposed use pattern: Two foliar sprays at 0.15 lb ai/A/application for a seasonal rate of 0.3 lb ai/A with a 0
- day PHI. Dill weed 0.81
- 0.82 0 8 3.98 19.54 19.01 9.66 10.46 5.79 Dill Seed 0.80
- 0.83 0 6 3.60 22.60 21.20 18.30 14.45 8.34 1 n = number of samples, typically 2X number of trials. Min = lowest replicate sample value. Max = highest replicate sample value. HAFT = highest average field trial. STMdR = median of average field trials. Mean = mean of average field trials.Page **46** of **46**

**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
- chlorophenyl)
- 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
- chloroph enyl)
- 1 H

pyrazol
- 3
- yl]oxy]methyl]phenyl]met hoxycarbamate, including the metabolite [2
- [[[1
- (4
- chlorophenyl)
- 1 H

pyrazol
- 3
- yl]oxy]methyl]phenyl]car bamate - Py raclostrobin. Residue is NOT fat soluble.

Commodity 1 Tolerance (ppm) /Maximum Residue Limit ( ppm ) US Canada Mexico 2 Codex 3 Herb, subgroup 19A (fresh and dried) 40 None None Dill , seed 40 None None Nut , tree, group 14
- 12, except pistachio 0.04 0.04 0.02 (*) F ruit , stone, group 12
- 12 2.5 0.7 (apricot, nectarine, peach, plumcot, plum cherries) Cherries 3; Peach/nectarine 0.3; Plum 0.8

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.