**EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR**

**PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER EPA**  **Registration Division contact:**  **Andrew Ertman (703)**  **- 308**  **- 9**  **367 PP #2E8069**  EPA has received a pesticide petition **( 2E8069**  **)** from **Interregional Research**  **Project Number 4 (IR -**  **4), 500 College Road East, Suite 201W, Princeton, NJ 08540** proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 34 6a(d), to amend 40 CFR part 180 to establish new tolerances for py raclostrobin, carbamic acid, [2

- [[[1

- (4

- chlorophenyl)

- 1H

-py razol

- 3

- yl ]oxy]methyl]phenyl]methoxy

- , methyl ester and its metabolite methyl

-N

- [[[1

- (4

- chlorophenyl ) p yrazol

- 3

-yl ]oxy]o

- tolyl] carbamate (BF 500

- 3); expressed as parent compound in or on the raw agricultural commodity **A rtichoke, globe**  at **3 .0**  parts per million (ppm); **E ndive, Belgium**  at **3 .0**  ppm ; **Persimmon** at **3 .0**  ppm ; and updating existing crop groups to **Vegetable , bulb, group**  **3 -**  **07** at **0 .9**  ppm **; Vegetable, fruiting,**  **group 8**  **- 10**  at **1. 4**  ppm ; **Fruit, c itru**  **s , g**  **roup 10 -**  **10** at **2.0** ppm ; **Fruit, pome, group 11 -**  **10** at **1.5** ppm; **O ilseed**  **, g**  **roup 20** at **0 .**  **4 5**  ppm ; **Caneberry s**  **ubgroup 13 -**  **07A** at **4 .0**  ppm ; **Bushberry Subgroup 13 -**  **07B** at **4.0** ppm ; **Small f**  **ruit ,**  **v ine**  **c limbing**  **s ubgroup**  **(except fuzzy kiwi) 13**  **- 07F**  at **2 .0**  ppm ; and **Low g**  **r owing**  **b erry**  **s ubgroup 13**  **- 07G**  at **1.2** ppm ; and to amend 40 CFR part 180 b y removing a tolerance for residues of **[**py raclostrobin, carbamic acid, [2

- [[[1

- (4

- chlorophenyl)

- 1H

-py razol

- 3

- yl ]oxy]methyl]phenyl]methoxy

- , methyl ester and its metabolite methyl

-N

- [[[1

- (4

- chlorophenyl ) p yrazol

- 3

-yl ]oxy]o

- tolyl] carbamate (BF 500

- 3); expressed as parent compound**]** in or on the raw agricultural commodity **B erry**  , **group 13**  at **4.0** ppm ; **Fruit, citrus, group 10**  at **2.0** ppm ; **Fruit, pome, group 11** at **1.5** ppm ; **Grape** at **2.0** ppm ; **Stra wberry**  at **1.2** ppm ; **Vegetable, bulb, group 3** at **0.9** ppm ; **Vegetable, fruiting, group 8**  at **1. 4**  ppm ; **Bo rage**  **, seed** at **0.45** ppm **; C**  **astor oil plant , seed**  at **0.45** ppm **; Chinese tallowtree**  **, seed** at **0.45** ppm **; Cr**  **am be**  **, seed** at **0.45** ppm **; C uphea**  **, seed** at **0.45** ppm **; E chium**  **, seed**  at **0.45** ppm ; **E uphorbia**  **, seed** at **0.45** ppm **; E vening primrose**  **, seed**  at **0.45** ppm ; **F lax seed**  at **0.45** ppm **; G old of pleasure**  **, seed** at **0.45** ppm ; **H are’s**  **ear mustard , seed**  at **0.45** ppm**, J ojoba**  **, seed** at **0.45** ppm ; **L esquerella**  **, seed** at **0.45** ppm**, L unaria**  **, seed** at **0 .45**  ppm **; M eadowfoam**  **, seed** at **0.45** ppm; **M ilkweed**  **, seed** at **0.45** ppm **; M ustard**  **, seed**  at **0.45** ppm ; **N iger seed**  **, seed** at **0.45** ppm **; O**  **il radish , seed**  at **0.45** ppm **; P oppy** **, seed**  at **0.45** ppm **; R apeseed**  **, seed** at **0.45** ppm **; R** **ose hip , seed**  at **0.45** ppm **; S afflower** **, seed** at **0. 45**  ppm ; **S esame**  **, seed** at **0.45** ppm ; **S tokes aster** **, seed** at **0.45** ppm ; **S unflower**  **, seed** at **0.45** ppm ; **S weet rocket**  **, seed** at **0.45 ppm, T**  **allowwood , seed**  at **0.45 ppm, T ea oil plant** **, seed** at **0.45 ppm, and V**  **ernonia , seed**  at **0.45** ppm . EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not fully evaluated the sufficiency

of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition. A. Residue Chemistry 1. Plant metabolism. **Plant and animal metabolism. Nature of the residue**2

**studies (OPPTS 860.1300) were conducted in grape, potato and wheat as representative crops in order to charact**  **erize the fate of pyraclostrobin in all crop ma**  **trices. Pyraclostrobin demonstrated a similar pathway and fate in all three crops. In all three crops the pyraclostrobin Residues of Concern (ROC) of were**  **characterized as parent (pyraclostrobin) and BAS 500 -** **3), methyl -** **N[[[1 -**  **(4 -**  **chlorophenyl) pyrazol -** **3yl]oxy]o -** **tolyl] carbamate. In hens the residues of concern were determined to be parent compound and a hydroxlated metabolite, BAS 500**  **- 16.**  **In goats the residues of concern were determined to be parent and a hydr oxylated**  **metabolite BAS 500 -**  **10 .**  2. Analytical method. **In plants the method of analysis is aqueous organic solvent extraction, column clean up and quantitation by LC/MS/MS. In animals the**  **method of analysis involves base hydrolysis, organic extraction, column clean up**  **and quantitation by LC/MS/MS or derivatization (methylation) followed by quantitation by GC/MS**  **.** 3. Magnitude of residues. **Field trials were carried out in order to determine the magnitude of the residue**  **s in**  **globe artichoke, globe; endive, Blegium; and**  **persimmon ,**  **to satisfy the requirements for a tolerance of pyraclostrobin in th ese**  **commodit ies**  **. Field trials were carried out using the maximum proposed labeled rate, maximum proposed number of applications, and the minimum proposed pre**  **** **harve st interval.**  **No additional data were needed in support of residues in meat, milk, poultry and eggs**  **.** B. Toxicological Profile 1. Acute toxicity. **Pyraclostrobin and its formulated products have favorable acute toxicity. The acute toxicity studies place**  **technical pyraclostrobin in toxicity category IV for acute oral and acute inhalation and category III for acute dermal.**  **Pyraclostrobin is category III for both eye and skin irritation, and it is not a dermal sensitizer. Two formulated end use products a**  **re proposed, an Emulsifiable Concentrate (EC) and an Extruded Granule (EG). The EC has an acute oral**  **toxicity category of II, acute dermal of III, acute inhalation of IV, eye and skin irritation categories of III, and is not a dermal sensitizer. The EG h**  **as acute oral and dermal toxicity categories of III, acute inhalation of IV, eye irritation of III,**  **skin irritation of IV and is not a dermal sensitizer .**  2. Genotoxicty. **Pyraclostrobin was negative for inducing mutations in both an in vitro Ames test and**  **an in vitro CHO/HGPRT Locus Mammalian Cell Mutation Assay. Pyraclostrobin also demonstrated no chromosomal effects in an in vitro V79**  **Cells CHO Cytogenetic Assay and an in vivo Mouse Micronucleus test. An additional in vitro study investigating DNA dama**  **ge and repair also showed no effects. Pyraclostrobin has been tested in a total of 5 genetic toxicology assays**  **consisting of in vitro and in vivo studies. It can be stated that pyraclostrobin did not show any mutagenic, clastogenic or other genotoxic acti** **vity when tested under the conditions of the studies mentioned above. Therefore, pyraclostrobin does not pose** 3

**a genotoxic hazard to humans .**  3. Reproductive and developmental toxicity. **The reproductive and developmental toxicity of pyraclostrobin was inv**  **estigated in a 2 -**  **generation rat reproduction study as well as in rat and rabbit teratology studies. There were no**  **adverse effects on reproduction, systemic toxicity to adults or developmental toxicity in the two**  **- generation study so the NOAEL is the highes**  **t dose tested of 300 ppm (ap**  **proximately 32.6 mg/kg bw/day). No teratogenic effects were noted in either the rat or rabbit developmental studies.**  **In the rat study, maternal toxicity observed at the mid and high dose consisted of decreased food consumption**  **and body weight gain. Developmental changes noted at the high dose were increased incidences of dilated renal pelvis and cervical ribs**  **with no cartilage. The maternal NOAEL was 10 mg/kg bw and the developmental NOAEL was 25 mg/kg bw.**  **In the rabbit tera tology study, maternal toxicity observed at the mid and high doses**  **consisted of decreased food consumption and body weight gain (severe at the high dose). An increased postimplantation loss was also observed at the mid and high**  **doses due to an increase in early resorptions. In rabbits, these types of effects are**  **often observed with significant stress on the mothers (as seen by the body weight gain decrease in this study) and not indicative of frank developmental toxicity. The**  **NOAEL for both maternal and developmental toxicity was 5 mg/kg bw**  **.** 4. Subchronic toxicity. **The subchronic toxicity of pyraclostrobin was investigated in 90**  **- day feeding studies with rats, mice and dogs, and in a 28**  **- day**  **dermal administration study in rats. A 90 -**  **day neurotoxicity stu dy in rats was also**  **performed. Generally, mild toxicity was observed. At high dose levels in feeding studies, general findings in all three species were decreased food consumption and**  **body weight gain and a thickening of the duodenum. Anemia occurred at high dose**  **levels in both rats and mice with accompanying extramedullary hematopoiesis of the spleen in rats. In rats only, a finding of liver cell hypertrophy was indicative of a**  **physiological response to the handling of the chemical. The lowest NOAEL in the**  **90 -**  **day feeding studies was from the dog study and determined to be 5.8 mg/kg bw/day.**  **In the 28 -**  **day repeat dose dermal study, no systemic effects were noted up to the highest dose tested of 250 mg/kg bw/day.**  **In a 90 -**  **day rat neurotoxicity study, a direct neurotoxic effect was not observed**  **.** 5. Chronic toxicity. **Py raclostrobin was administered to groups of 5 male and**  **5 female purebred Beagle dogs in the diet at concentrations of 0, 100, 200 and 400 ppm over a period of 12 months. Signs of toxici** **ty were observed at the high dose. Diarrhea was observed throughout the study period for both sexes. High dose males**  **and females initially lost weight and body weight gain was decreased for the entire study period for females. Hematological changes obser** **ved were an increase in**4

**white blood cells in males, and an increase in platelets in both sexes at the high dose. Clinical chemistry demonstrated a decrease in serum total protein, albumin,**  **globulins and cholesterol in high dose animals of both sexes possi bly due to the**  **diarrhea and reduced nutritional status of the animals. The NOAEL was 200 ppm (ca. 5.5 mg/kg bw/day males; 5.4 mg/kg bw/day females).**  **In an oncogenicity study, pyraclostrobin was administered to groups of 50 male and 50 female Wistar rats**  **at dietary concentrations of 0; 25; 75, and 200 ppm for 24 months. In a companion chronic toxicity study, 20 rats/sex were used at the same**  **dose levels as in the oncogenicity study. A body weight gain depression of 10 -**  **11% in males and 14**  **- 22% in females**  **with an accompanying decrease in food efficiency was observed at the high dose. There was no evidence that pyraclostrobin produced**  **a carcinogenic effect in rats. The NOAEL for the chronic rat and the cancer rat study is 75 ppm (ca. 3.4 mg/kg bw/day males**  **; 4.7 mg/kg bw/day females). Pyraclostrobin was administered to groups of 50 male and 50 female B6C3F1 mice**  **at dietary concentrations of 0, 10, 30, 120 and 180 ppm (females only) for 18 months. Body weights were reduced at the highest doses tested in bot** **h males and females. At the high dose, body weight gain decreases of 27% in females and 29% in males**  **with an accompanying decrease in food efficiency were observed. No other signs of toxicity were noted at any dose level. The NOAEL was found to be 30 p**  **pm (ca. 4.1 mg/kg bw/day) for males. The Agency determined that the body weight effect at the**  **high dose in females was not sufficient to determine an MTD. Therefore the NOAEL for females is considered greater than the highest dose tested of 32.8 mg/kg**  **bw/ day. There was no evidence that pyraclostrobin produced a carcinogenic effect**  **in mice .**  6. Animal metabolism. **In a rat metabolism study with pyraclostrobin, 10 -**  **13% of the administered dose was excreted in the urine and 74**  **- 91% in the feces within 48**  **hour s. Excretion via bile was significant accounting for 35**  **- 38% of the administered**  **dose. By 120 hours after dosing, very little radioactivity remained in tissues. Pyraclostrobin was rapidly and almost completely metabolized. Very little**  **unchanged parent was detected. The phase one biotransformation is characterized**  **by N -**  **demethoxylation, various hydroxylations, cleavage of the ether bond and further oxidation of the two resulting molecule parts. Conjugation of the formed**  **hydroxyl groups by glucuronic acid o r sulfate also occurred. In summary,**  **pyraclostrobin is extensively metabolized and rapidly eliminated primarily via the bile, with no evidence of accumulation in tissues**  **.** 7. Metabolite toxicology

. **A comparison of the rat metabolism results with the plant**  **metabolism/residue results indicates that toxicology studies performed with the parent pyraclostrobin are sufficient to cover dietary exposure. Plant residues**  **are primarily the parent compound with a fraction (up to 10 -**  **20% at most) being the demethoxylat**  **ed parent. This metabolite is referred to as BF 500 -** **3 in the plant studies and as 500M07 in the rat study. This metabolite in the rat is the first step in**  **the major biotransformation process leading to the majority of the metabolites determined in the ma** 

**jor excretion pathway .** 5

8. Endocrine disruption

. **Endocrine effects. No specific tests have been conducted with pyraclostrobin to determine whether the chemical may have an**  **effect in humans that is similar to an effect produced by a naturally occurring est**  **rogen or other endocrine effects. However, there were no significant findings in other relevant toxicity studies (i.e., subchronic and chronic toxicity, teratology and**  **multi -**  **generation reproductive studies) which would suggest that pyraclostrobin produces**  **endocrine related effects .**  C. Aggregate Exposure 1. Dietary exposure. **Exposure assessments were conducted to evaluate the potential risk due to acute and chronic dietary exposure of the U.S. population and**  **all sub -** **populations. The consumption data**  **was from the NHANES 2 -**  **day food consumption data for 2003 to 2008 and the assessment was performed using the**  **Dietary Exposure Evaluation Module (DEEM -** **FCID) software version 3.14. An assessment for water in the diet was performed in a separate analysis.**  **The assessments used 100 % crop treated and included all commodities with established**  **tolerances and proposed tolerances submitted in May 2012 and the commodities proposed in this submission for tolerances as follows: artichoke, Belgium endive and**  **persimmon. In addition tolerances for the following recently established groups or**  **subgroups were used as follows: Berry and small fruit crop group 13 -**  **07, Fruit, citrus, crop group 10**  **- 10, Fruit, pome, crop group 11**  **- 10, Oilseed, crop group 20,**  **Vegetable, bulb, crop group 3**  **- 07, Vegetable, fruiting crop group 8**  **- 10. The impact**  **of the new commodities on the animal Maximum Reasonably Balanced Diets was minimal and thus no changes in tolerances in animal commodities are proposed.** 

i. Food. **Acute Dietary Exposure Assessme nt**  **The inputs for previously registered commodities were based on tolerance values or highest average field trial (HAFT) residues as used in the acute dietary assessment**  **conducted as part of the evaluation by EPA in February 11, 2008 (DP Number 348308). A**  **few input values were changed from the 2008 evaluation as follows: the HAFT of 10.7 mg/kg was used for the whole subgroup 4B (as was done in the EPA**  **2005 analysis) rather than just for celery; the HAFT of 14.4 mg/kg was used for the radicchio (as was don**  **e in the EPA 2005 analysis) in addition to head lettuce; the HAFT of 21.2 mg/kg rather than 20.1was used for the leaf lettuce; the group**  **tolerance of 2.5 was used for all stone fruit; the group tolerance of 0.45 was used for all oilseed except cotton seed**  **. Process factors derived from experimental studies that differed from those used in the 2008 evaluation were used as follows: grape juice =**  **0.14, tomato paste = 0.6, tomato puree = 0.3, tomato juice = 0.3. The resulting exposure estimates were compared**  **against the pyraclostrobin (BAS 500 F) acute Population Adjusted Dose (aPAD) of 3.00 mg/kg b.w./day for all**  **populations except females age 13 -**  **49 years with an aPAD of 0.05 mg/kg b.w./day. The most highly exposed sub**  **- population was females 13**  **- 49 years old w** **ith 84.3 %** 6

**utilization of the aPAD. The results of the acute dietary assessment are presented in Table 1.**  **Table 1.**  **Results for**  **Pyraclostrobin (BAS**  **500 F)**  **Acute Dietary**  **Exposure (Food**  **only) Considering**  **all Current**  **and Proposed**  **Tolerances using**  **DEEM -**  **FCID at**  **the 95**  **th Percentile** 

**Population Exposure Estimate**  **% aRfD Subgroups**  **(mg/kg b.w./day) U.S. Population**  0.042652 1.42 **All Infants (< 1 year old)** 0.055319 1.84 **Children (1 -**  **2 years old)** 0.079562 2.65 **Children (3 -**  **5 years old)** 0.070094 2.34 **Children (6 -**  **12 y ears old)**  0.041602 1.39 **Youth (13 -**  **19 years old)** 0.030026 1.00 **Adults (20 -**  **49 years old)** 0.039469 1.32 **Adults (50+ years old)** 0.039328 1.31 **Females (13 -**  **49 years old)** 0.042158 84.32 **Th e results of the analysis show that for all populations, the estimate**  **d exposures are below the Agency's level of concern (< 100% aPAD). Additional refinements in the**  **dietary risk assessment (i.e. utilizing additional anticipated residue values, percent crop treated values) would further reduce the estimated exposure values.**  **Chronic Dietary Exposure Assessment The inputs for previously registered commodities were based on tolerance values or**  **average field trial residues as used in the chronic dietary assessment conducted as part of the evaluation by EPA in February 11, 2008**  **(DP Number 348308). A few input values were changed from the 2008 evaluation as follows: the HAFT of 0.21**  **mg/kg was used for the subgroup 6C (except chickpea, guar and lentil at 0.34 mg/kg) rather than the tolerance; the group tolerance of 2.5 was used f**  **or all stone fruit; the group tolerance of 0.45 was used for all oilseed except cotton seed. Process**  **factors derived from experimental studies that differed from those used in the 2008 evaluation were used as follows: grape juice = 0.14, tomato paste = 0.6**  **, tomato puree = 0.3, tomato juice = 0.3.**  **The resulting exposure estimates were compared against the pyraclostrobin chronic Population Adjusted Dose (cPAD) for the U.S. population and all sub**  **- populations of**  **0.034 mg/kg bw/day. This endpoint is based on t he NOAEL value of 3.4 mg/kg**  **bw/day using a FQPA safety factor of 1. The most highly exposed population sub**   ** group was children 1** **- 2 years of age which utilized 55.8% cPAD. The results of the**  **chronic dietary assessment (food only) are presented in Table 2 .**  **Table 2. Results for Pyraclostrobin (BAS 500 F)**  **Chronic Dietary Exposure (Food only) Considering All Commodities using DEEM** **- FCID** 7 **Population Exposure Estimate**  **% cPAD Subgroups**  **(mg/kg b.w./day) U.S. Population**  **0.006239 18.4**  **All Infants (< 1 year old) 0.011203**  **33.0 Children (1**  **- 2 years old)**  **0.018972 55.8**  **Children (3 -**  **5 years old) 0.013556**  **39.9 Children (6**  **- 12 years old)**  **0.007481 22.0**  **Youth (13 -**  **19 years old) 0.003982**  **11.7 Adults (20**  **- 49 years old)**  **0.005205 15.3**  **Adults (50+ years old) 0.005617**  **16.5 Fe**  **males (13 -**  **49 years old) 0.005012**  **14.7 The results of the risk assessment**  **show that for all populations the exposures are below a level of concern (< 100% cPAD). Additional refinements in the dietary risk**  **assessment (i.e. utilizing anticipated residue val ues, percent crop treated values)**  **would further reduce the estimated exposure values.**  ii. Drinking water. **The water exposure values used for this analysis are from the most recent EPA assessment for pyraclostrobin (February 11, 2008,**  **“Pyraclostrobin. Acu te and Chronic Aggregate Dietary (Food and Drinking water)**  **Exposure and Risk Assessment to Support new Uses on Oat Grain, Barley, Oilseed (Crop group 20), Fresh Herbs (Herbs Subgroup 10=9A), Avocado, Black Sapote,**  **Canistel, Mamey Spoted, Mango, Papaya, Sap odilla, and Star Apple.” The highest**  **water exposure values were from aerial application on ornamentals which resulted in an acute exposure of 35.6 ug/L and chronic exposure of 2.3 ug/L. These water**  **exposure values are greater than the exposure from the c urrent uses**  **and the proposed new uses**  **. Acute:**  **The highest acute Estimated Drinking Water Concentration (EDWC) for pyraclostrobin (BAS 500 F) was estimated to be 35.6**  **μ g/L (ppb) in surface water.**  **The analysis was performed using DEEM** **- FCID software versi**  **on 3.14 with the residue concentration in water set at 0.0356 mg/L based on the surface water**  **concentration determined for the nursery use. The resulting exposure estimates were compared against the pyraclostrobin (BAS 500 F) acute Population Adjusted**  **Dose (aPAD) of 3.00 mg/kg b.w./day for all populations except females age 13**  **- 49**  **years with an aPAD of 0.05 mg/kg b.w./day. The most highly exposed sub**   ** population was females 13** **- 49 years old with 3.9**  **% utilization of the aPAD. The results of the acute dietary a**  **ssessment for water are presented in Table 3. Table**  **3. Results**  **for Pyraclostrobin**  **(BAS 500**  **F) Acute**  **Dietary Exposure**  **(Water only)**  **Considering all**  **Current and**  **Proposed Uses**  **using DEEM** **- FCID**  **at the**  **95 th**  **Percentile Population**  **Exposure Estimate % aRfD** 

**Subgrou ps**  **(mg/kg b.w./day)**8 **U.S. Population 0.001941**  **0.06 All Infants (< 1 year old)**  **0.00608 0.20**  **Children (1 -**  **2 years old) 0.002993**  **0.10 Children (3**  **- 5 years old)**  **0.002429 0.08**  **Children (6 -**  **12 years old) 0.001856**  **0.06 Youth (13**  **- 19 years old)**  **0.001617 0.05**  **Ad ults (20**  **- 49 years old)**  **0.00191 0.06**  **Adults (50+ years old) 0.001702**  **0.06 Females (13**  **- 49 years old)**  **0.001937 3.87** 

**Chronic: The highest chronic Estimated Drinking Water Concentration (EDWC)**  **for pyraclostrobin (BAS 500 F) was estimated to be 2.3 μ**  **g/L (pp b) in surface water.**  **The analysis was performed using DEEM** **- FCID software version 3.14 with the**  **residue concentration in water set at 0.0023 mg/L based on the surface water concentration determined for the nursery use. The resulting exposure estimates**  **were compared against the pyraclostrobin chronic Population Adjusted Dose**  **(cPAD) for the U.S. population and all sub -** **populations of 0.034 mg/kg bw/day. The most highly exposed population sub**  **- group was infants less than 1 year of age which**  **utilized 0.4% cPAD. The results of the chronic dietary assessment (water only) are**  **presented in Table 4 .**  **Table 4. Results for Pyraclostrobin (BAS 500 F)**  **Chronic Dietary Exposure (Water only)**  **Considering all Current and Proposed Uses using DEEM** **- FCID** 

**Population Exposure Est** **imate % cPAD**  **Subgroups (mg/kg b.w./day)**  **U.S. Population 0.000048**  **0.1 All Infants (< 1 year old)**  **0.000124 0.4**  **Children (1 -**  **2 years old) 0.000069**  **0.2 Children (3**  **- 5 years old)**  **0.000059 0.2**  **Children (6 -**  **12 years old) 0.000042**  **0.1 Youth (13**  **- 19 years old)**  **0.000035 0.1**  **Adults (20 -**  **49 years old) 0.000048**  **0.1 Adults (50+ years old)**  **0.000048 0.1**  **Females (13 -**  **49 years old) 0.000048**  **0.1 Acute Aggregate Exposure and Risk (Food and water)**  **The aggregate acute risk includes residues of pyraclostrobin from food and water**  **(Table 5). Exposures from residential uses are not included in the acute aggregate assessment. The results demonstrate that there are no safety concerns for any**  **subpopulation based on established and new uses, and that the results clearly meet the**  **FQ PA standard of reasonable certainty of no harm.** 9

**Table 5. Estimated**  **Acute Aggregate**  **Exposure and**  **Risk of**  **Pyraclostrobin**

**(Food and Drinking Water) Population Subgroup**  **Food Exposure**  **(mg/kg/day) Water** 

**Exposure (mg/kg/day)**  **Total**

**Exposure (mg/kg/day)**  **% aPA D**  **U.S. Population 0.042652**  **0.001941 0.044593**  **1.5 All Infants (< 1 yr**  **old) 0.055319**  **0.006080 0.085642**  **2.9 Children 1**  **- 2 years**  **0.079562 0.002993**  **0.073087 2.4**  **Children 3 -**  **5 years 0.070094**  **0.002429 0.044031**  **1.5 Children 6** 

**– 12 years**  **0.041602 0.001856**  **0.0318 82**  **1.1 Youth 13**  **- 19 years**  **0.030026 0.001617**  **0.041086 1.4**  **Females 13 -**  **49 years 0.042158**  **0.001937 0.044095**  **88.2 Adults 20**  **- 49 years**  **0.039469 0.001910**  **0.041238 1.4**  **Adults + 50 0.039328**  **0.001702 0.043860**  **1.5**

**Short -**  **and Intermediate**  **Term Aggregate**  **Exposure and**  **Risk (food,**  **water, and**  **residential) Short** **- term**  **aggregate risk**  **from pyraclostrobin**  **takes into**  **account exposures**  **from dietary**  **consumption (food**  **and water)**  **and residential**  **exposure from**  **turf use.**  **P ost**  **application exposure**  **from the**  **turf use**  **is considered**  **short -** **term. T**  **he aggregate**  **MOEs from**  **food, water,**  **and residential**  **exposure are**  **105 and**  **229 for**  **children 1**  **- 2**  **years old**  **and the**  **US population,**  **respectively. T**  **hese MOEs**  **are greater**  **than the**  **target MOE**  **of 100**  **which indicates**  **there is**  **no safety**  **concern. T**  **he results**  **of the**  **analysis are shown in Table 6. Table 6.**  **Estimated Short/Intermediate Term Aggregate Exposure and Risk of**

**Pyraclostrobin (Food, Drinking Water, and Residential exposure)**

**Population Target** 

**MOE 1**  **Food Exposure**  **(mg/kg/day) Water** 

**Exposure (mg/** **kg/day) Residential** 

**Exposure (mg/kg/day)**  **Total**

**Exposure (mg/kg/day)**  **MOE 2**  **US 100**  **0.00624 0.000048**  **0.0190 0.0253**  **229 Child 1**  **- 2 yr**  **old 100**  **0.01897 0.000069**  **0.0364 0.0554**  **105 1**  **Target MOE is 100. 2**  **Aggregate MOE = (NOAEL / (Food + Water + Residential Exposu re), NOAEL =**  **5.8 mg/kg b.w./day.**10

**Chronic Aggregate Exposure and Risk (food and water) The**  **aggregate chronic**  **risk includes**  **residues of**  **pyraclostrobin from**  **food and**  **water (Table**  **7). Exposures**  **fr om**  **residential uses**  **are not**  **included in**  **the chronic**  **aggregate assessment.**  **T he**  **results demonstrate**  **there are**  **no safety**  **concerns for**  **any subpopulation**  **based on**  **established and**  **new uses,**  **and that**  **the results**  **clearly meet**  **the FQPA standard of reasonable certainty of no harm. Table 7.**  **Estimated Chronic Aggregate Exp osure and Risk of Pyraclostrobin**  **(Food and Drinkiing water) Population Subgroup**  **Food Exposure**  **(mg/kg/day) Water** 

**Exposure (mg/kg/day)**  **Total**

**Exposure (mg/kg/day)**  **% cPAD U.S. Population**  **0.006239 0.000048**  **0.006287 18.5**  **All Infants (< 1 yr old) 0.011203**  **0.0 00124**  **0.011327 33.3**  **Children 1 -**  **2 years 0.018972**  **0.000069 0.019041**  **56.0 Children 3**  **- 5 years**  **0.013556 0.000059**  **0.019031 56.0**  **Children 6**

**– 12 years**  **0.007481 0.000042**  **0.007523 22.1**  **Youth 13 -**  **19 years 0.003982**  **0.000035 0.004017**  **11.8 Females 13**  **- 49 years**  **0.005 012**  **0.000048 0.005060**  **14.9 Adults 20**  **- 49 years**  **0.005205 0.000048**  **0.005253 15.5**  **Adults + 50 0.005617**  **0.000048 0.005665**  **16.7** 2. Non

- dietary exposure

. **Pyraclostrobin is registered for use on residential and recreational turf. The applications to turf wi** **ll be made only by professional pest control operators. Therefore, residential handler exposure was not evaluated. The exposure**  **assessment cited in this notice of filing was transcribed from the Federal Register Notice on pyraclostrobin (U.S. EPA final r**  **ule published in the Federal Register October 29, 2004 [Vol 69, No. 209, p 63083** 

**– 63100). The EPA evaluated the**  **following post -**  **application exposure scenarios 1) adults and toddler post -**  **application dermal exposure 2) toddlers’ incidental ingestion of pest** **icide residues on lawns form hand**  **- to**  **- mouth transfer, 3) toddlers’ object** **- to**  **- mouth transfer from mouthing**  **pesticide -** **treated turfgrass, and 4) toddlers’ incidental ingestion of soil from pesticide**  **- treated residential areas. A dermal absorption value of 14%**  **was used in the assessment of pyraclostrobin. The exposure and risk estimates for the residential**  **exposure scenarios are assessed for the day of application because adults and toddlers could contact treated turf immediately after application. All short** **- /i**  **ntermediate term MOEs were greater than 100 which indicates that exposure from all residential scenarios result in exposures below a level of concern**  **.** D. Cumulative Effects **Section 408(b)(2)(D)(v) requires that, when considering whether to establish, modi**  **fy, or revoke a tolerance, the Agency consider ``available information'' concerning the cumulative effects of a particular pesticide's residues**  **and ``other substances that have a common mechanism of toxicity.' Pyraclostrobin**11

**is a foliar fungicide which be longs to the class of strobilurin chemistry. It is a**  **synthetic analog of strobilurin A, a naturally occurring antifungal metabolite of the mushroom Strobillurus tenacellus (Anke et. al., 1977). The active ingredient acts in**  **the fungal cell through inhibit ion of electron transport in the mitochondrial**  **respiratory chain at the position of the cytochrome -** **bc1 complex. The protective effect is due to the resultant death of the fungal cells by disorganization of the fungal**  **membrane system. Pyraclostrobin also acts curatively to prevent the increase and**  **spread of fungal infections by inhibiting mycelial growth and sporulation on the leaf surface. Pyraclostrobin inhibits spore germination, germ tube growth and**  **penetration into the host tissues The EPA is current** **ly developing methodology to perform cumulative risk assessments. At this time, there is no available data to determine whether**  **pyraclostrobin has a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk a**  **ssessment. Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common**  **mechanism of toxicity, pyraclostrobin does not appear to produce a toxic metabolite common to other substances**  **.** E. Safety Determination 1. U.S. po pulation. **Based on this risk assessment, BASF concludes that there is a reasonable certainty that no harm will result to the general population from the**  **aggregate exposure to pyraclostrobin from the existing and proposed new uses.** 2. Infants and children

. **Based on this risk assessment, BASF concludes that there is a reasonable certainty that no harm will result to infants or children from**  **the aggregate exposure to pyraclostrobin from the existing and proposed new uses.** F. International Tolerances **No Co dex maximum residue levels (MRLs) have been established for**  **residues of pyraclostrobin. Therefore, no tolerance discrepancies exist between countries for this chemical.**