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

**PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER EPA**  **Registration Division contact:**  **[ Tony Kish, Product Manager 22 (703)**  **- 308**  **- 9443**  **] Pyraclostrobin**  **sugarcane .**  **INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In**  **cases where the outline element does not apply, please insert “NA -** **Remove” and maintain the outline. Please do not change the margins, font, or**  **format in your pesticide petition. Simply replace the instructions that appear in**  **green , i.e., “**  **[ insert**  **company name ]**  **,” with the information specific to your action. TEMPLATE:**  **[ BASF Corporation**  **] [**  **2F8038 ]**  EPA has received a pesticide petition **2F8038** from **BASF Corporation ,**  **PO Box 13528, Research Triangle Park, North Carolina, 27709**  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

-tol yl ] carbamate (BF 500

- 3); expressed as parent compound in or on the raw agricultural commodity **sugarcane, cane**  at **0.2** parts per million (ppm). No tolerances are proposed for the processed commodities, refined sugar and molasses, as no concentration of p yraclostrobin residues are expected in these commodities. 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 studies (OPPTS 860.1300) were conducted in grape, potato and wheat as**  **representative crops in order to characterize 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) an**  **d BAS 500 -** **3), methyl -** **N[[[1 -**  **(4 -** 2

**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 hydroxylated**  **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 e xtraction, 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**  **sugarcane and the pr** **ocessed commodities, refined sugar and molasses,**  **to satisfy the requirements for a tolerance of pyraclostrobin in th**  **i s**  **commodity . Field trials were carried out using the maximum proposed labeled**  **rate, maximum proposed number of applications, and the minim um** **proposed pre****** **harvest interval. B**  **ased on the results of a processing study, residues of pyraclostrobin do not concentrate in refined sugar or molasses. The use in sugarcane does not result in a**  **maximum reasonable feed burden for cattle, poultry or swi ne in excess of that**  **already determined for registered uses. 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 favorabl e**  **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 der mal**  **sensitizer. Two formulated end use products are 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 has 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 in ducing 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. A n**  **additional in vitro study investigating DNA damage 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 activity 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 an d**  **developmental toxicity of pyraclostrobin was investigated 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 t** **he two -**  **generation study so the NOAEL is the highest dose tested of 300 ppm (approximately 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 a**  **nd 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 deve** **lopmental NOAEL was 25 mg/kg bw.**  **In the rabbit teratology 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 obse rved 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 devel opmental 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 admin istration study in rats. A 90**  **- day neurotoxicity study 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 a nd 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 4 00**  **ppm over a period of 12 months. Signs of toxicity 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 st** **udy period for females. Hematological changes observed 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 possibly 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 adminis tered 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 ca ncer 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 wei**  **ghts were reduced at the highest doses tested in both 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 ppm (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 gr**  **eater 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 excret** **ed in the urine and 74 -**  **91% in the feces within 48 hours. 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 com** **pletely 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. Conjugat** **ion of the formed hydroxyl groups by glucuronic acid or 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 demethoxylated 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 major 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 estrogen 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 acut e and chronic dietary exposure**  **to residues o f**  **pyraclostrobin. This analysis includes all currently registered uses and the**  **proposed new toleranc es in**  **sugarcane. The proposed new tolerance for**  **sugarcane, cane is 0.2 ppm**  **. The pyraclostrobin chronic**  **population adjusted dose (c** **PAD) is 0.034 mg/kg b**  **w/day based on the NOAEL of 3.4 mg/kg bw/day in the rat chronic toxicity study** **, a standard safety factor of**  **100X and a FQPA**  **safety factor of 1X**  **. The acute population adjusted dose**  **(a PAD**  **) is 3 mg/kg b.w./day for all subpopulation except**  **females 13 -** **49 yea rs of age**  **based on a NOAEL from the acute neurotoxicity study of 300 mg/kg bw/day** **, a standard safety factor of 100X**  **and a FQPA safety factor**  **of 1X .**  **For females ages**  **13 -** **49 years, the a PAD**  **is 0.05 mg/kg b.w./day based on the NOAEL of 5 mg/kg bw/day from the**  **rabbit teratology study , a standard safety factor of**  **100X , and a FQPA**  **safety factor of 1X**  **.** i. Food. **[ Acute Dietary Exposure Assessment**  **The estimated**  **acute dietary**  **exposure is**  **based on**  **the proposed**  **tolerance of**  **0.2 mg/kg**  **for sugarcane**  **and tolerance**  **val ues**  **for all**  **registered commodities**  **except as**  **follows: use**  **of highest**  **average field**  **trial residues**  **of for**  **crop groups**  **4A (23.38**  **mg/kg) except**  **that specific**  **highest field**  **trial residues**  **were used**  **for head**  **lettuce (14.8**  **mg/kg), leaf**  **lettuce (21.2**  **mg/kg) and**  **c rop**  **groups 4b**  **celery (10.7**  **mg/kg) and**  **crop group**  **6C dry**  **bean (0.21**  **mg/kg) and**  **dry pea**  **(0.1 mg/kg).**  **E xperimental**  **processing factors**  **of 0.1**  **and 0.3**  **were used**  **for sugarcane,**  **refined sugar**  **and molasses,**  **respectively. E**  **xperimental processing**  **factors were**  **also used**  **for sugar**  **beet, sugar,**  **apple juice,**  **grape juice**  **, citrus**  **juice, cottonseed**  **oil, tomato**  **paste, tomato**  **puree, tomato**  **juice, soybean**  **oil, wheat**  **flour, wheat**  **germ and**  **mint oil**  **with default**  **process factors**  **used for**  **all other**  **commodities. The**  **evaluation us**  **ed 100%**  **crop treated. The consumption data was from the USDA Continuing Survey of Food Intake**  **by Individuals**  **(CSFII 1994**  **- 1996,**  **1998) and**  **the EPA**  **Food Commodity**  **Ingredient Database (FCID) using Exponent's Dietary Exposure Evaluation Module (DEEM** **- FCID)**  **sof**

**tware. The**  **results of**  **the assessment**  **for the**  **population of**  **females age**  **13 to**  **49 years**  **was a**  **utilization of**  **80.54% aPAD**  **at the**  **95 th**  **percentile based**  **on all**  **users, while**  **the highest**  **utilization for**  **all other**  **populations was**  **that of**  **children age 1**  **- 2 year at 2**  **.45% aRfD.**6

**Table 1. Results**  **for Pyraclostrobin**  **(BAS 500**  **F) Acute**  **Dietary Exposure**  **Analysis Considering**  **All Tolerances**  **and 100**  **% Crop**  **Treated using**  **DEEM -**  **FCID at the 95**  **th Percentile**  **(Food only) Population**  **Exposure Estimate %aPAD**  **Subgroups (mg/kg b.w./da** **y) U.S. Population**  **0.043299 1.44**  **All Infants (< 1 year old) 0.059113**  **1.97 Children (1**  **- 2 years old)**  **0.073358 2.45**  **Children (3 -**  **5 years old) 0.06372**  **2.12 Children (6**  **- 12 years old)**  **0.046582 1.55**  **Youth (13 -**  **19 years old) 0.034726**  **1.16 Adults (20**  **- 49 year**  **s old) 0.038416**  **1.28 Adults (50+ years old)**  **0.040873 1.36**  **Females (13**

**– 49 years old)**  **0.04027 80.5**  **Chronic Dietary Exposure Assessment BASF**  **has estimated**  **chronic dietary**  **exposure estimates**  **based on**  **the proposed**  **tolerance of**  **0.2 mg/kg**  **for sugarcane**  **and tolerance**  **values for**  **all registered**  **commodities except**  **as follows:**  **use of**  **average field**  **trial residues**  **for crop**  **group 4A**  **(11.77 mg/kg)**  **except for**  **specific values**  **for head**  **lettuce (0.59**  **mg/kg) and**  **leaf lettuce(7.68 mg/kg), for crop group 4b (5.02 mg/kg),**  **for crop group 5a (1.10 mg/kg), for**  **crop group**  **5b (5.74**  **mg/kg), highest**  **residue for**  **crop group**  **6C (0.21**  **mg/kg), orange**  **(0.3 mg/kg),**  **apple (0.31**  **mg/kg) and**  **grape (0.768**  **mg/kg). ).**  **E xperimental**  **processing f** 

**actors of**  **0.1 and**  **0.3 were**  **used for**  **sugarcane, ref**  **ined sugar**  **and molasses,**  **respectively. E**  **xperimental processing**  **f actors**  **were also**  **used for**  **sugar beet,**  **sugar, apple**  **juice, grape**  **juice ,**  **citrus juice,**  **cottonseed oil,**  **tomato paste,**  **tomato puree,**  **tomato juice,**  **soybean oil,**  **wheat flour,**  **wheat germ**  **and mint**  **oil with**  **default process**  **factors used**  **for all**  **other commodities.**  **The evaluation**  **used 100%**  **crop treated. The consumption data was from the USDA Continuing Survey of Food Intake**  **by Individuals**  **(CSFII 1994**  **- 1996,**  **1998) and**  **the EPA**  **Food Commodity**  **Ingredient D atabase**  **(FCID) using Exponent's Dietary Exposure Evaluation Module**  **(DEEM -**  **FCID) software.**  **T he**  **exposure of**  **the general**  **population utilized**  **19.5% cRfD**  **while the**  **most highly**  **exposed population**  **sub -**  **group children**  **1 -** **2 years**  **of age**  **utilized 53.4% cPAD.**7

**Table 2 . Results for Pyraclostrobin (BAS 500 F) Chronic Dietary Exposure Analysis**  **Considering all**  **Tolerances and**  **100 %**  **Crop Treated**  **using DEEM** **- FCID**  **(Food only)**  **Population Exposure Estimate**  **%cPAD Subgroups**  **(mg/kg b.w./day) U.S. Population**  **0.006635 19.5**  **All I nfants (< 1 year old)**  **0.012892 37.9**  **Children (1 -** **2 years old) 0.018145**  **53.4 Children (3**  **- 5 years old)**  **0.013672 40.2**  **Children (6 -**  **12 years old) 0.008301**  **24.4 Youth (13**  **- 19 years old)**  **0.004877 14.3**  **Adults (20 -** **49 years old) 0.005276**  **15.5 Adults (50+ years o**  **ld) 0.005961**  **17.5 Females (13**  **- 49 years old)**  **0.005133 15.1**  **]** ii. Drinking water

. **[ The**  **water exposure**  **values used**  **for this**  **analysis are**  **from the**  **most recent**  **EPA assessment**  **for pyraclostrobin**  **(February 11,**  **2008, “Pyraclostrobin.**  **Acute and**  **Chronic Aggre**  **gate Dietary**  **(Food and**  **Drinking water)**  **Exposure and**  **Risk Assessment**  **to S**  **upport new**  **Uses on**  **Oat Grain**  **, Barley,**  **Oilseed (Crop**  **group 20),**  **Fresh Herbs**  **(Herbs Subgroup**  **10=9A), Av** **o cado,**  **Black Sapote,**  **Canistel, Ma**  **m ey**  **Spoted, Mango,**  **Papaya, Sapodilla,**  **and Star**  **App le.**  **” 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. Drinking**  **water contributions**  **were assessed**  **based on**  **the maximum**  **estimated pyraclostrobi** **n water concentrations (acute** 

**– 35.6 ug/L, chronic 2.3**  **ug/L), and water consumption**  **and body**  **weights reported**  **in CSFII,**  **using DEEM** **- FCID**  **software. The**  **acute and**  **chronic estimated**  **water exposure**  **values are**  **summarized in**  **Tables 3**  **and 4,**  **respectively. M** **inima l**  **exposure of**  **pyraclostrobin occur**  **s through**  **drinking water**  **with <**  **0.5 % t** **he aPAD and**  **cPAD for**  **all subpopulations with**  **the exception**  **of females 13**  **- 49 years of age with a**  **3.5 % aPAD.** 8

**Table 3. Results**  **for Pyraclostrobin**  **Acute Water**  **Exposure Analysis** 

**Consider ing**  **the Maximum**  **Estimated Acute**  **Drinking Water**  **Concentration using DEEM** **- FCID**  **Population Water Exposure Estimate**  **%aPAD Subgroups**  **(mg/kg b.w./day) U.S. Population**  **0.00186 0.06**  **All Infants (< 1 year old) 0.007012**  **0.23 Children (1**  **- 2 years old)**  **0.002918 0.10**  **Children (3 -**  **5 years old) 0.002666**  **0.09 Children (6**  **- 12 years old)**  **0.001856 0.06**  **Youth (13 -**  **19 years old) 0.001509**  **0.05 Females (13**  **- 49 years old)**  **0.001723 0.06**  **Adults (20 -** **49 years old) 0.001556**  **0.05 Adults (50+ years old)**  **0.001733 3.**  **5 aPAD = acut** **e population adjusted dose**9

**Table 4. Results**  **for Pyraclostrobin**  **Chronic Water**  **Exposure Analysis** 

**Considering the**  **Maximum Estimated**  **Chronic Drinking**  **Water Concentration using DEEM** **- FCID**  **Population Water Exposure Estimate**  **%cPAD Subgroups**  **(mg/kg b.w./day) U.S. Population**  **0.000048 0.1**  **All Infants (< 1 year old) 0.000159**  **0.5 Children (1**  **- 2 years old)**  **0.000072 0.2**  **Children (3 -**  **5 years old) 0.000067**  **0.2 Children (6**  **- 12 years old)**  **0.000046 0.1**  **Youth (13 -**  **19 years old) 0.000035**  **0.1 Females (13**  **- 49 years old)**  **0.000045 0.1**  **Adults (20 -** **49 years old) 0.000048**  **0.1 Adults (50+ years old)**  **0.000045 0.1**  **cPAD = chronic population adjusted dose Acute Aggregate Exposure and Risk (Food and water)**  **The aggregate acute risk includes residues of pyraclostrobin from food a nd 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 th**  **e FQPA standard of reasonable certainty of no harm. Table 5.**  **Estimated Acute**  **Aggregate Exposure**  **and Risk**  **of Pyraclostrobin** 

**(Food and Drinking Water) Population Subgroup**  **aPAD**

**(mg/kg/day) Food** 

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

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

**Exposur e**  **(mg/kg/day) %** 

**aPAD U.S. Population**  **3 0.043299**  **0.001860 0.045159**  **1.5 All Infants (< 1 yr**  **old) 3**  **0.059113 0.007012**  **0.080370 2.7**  **Children 1 -** **2 years 3**  **0.073358 0.002918**  **0.066638 2.2**  **Children 3 -**  **5 years 3**  **0.063720 0.002666**  **0.049248 1.6**  **Children 6**

**– 12 yea**  **rs 3**  **0.046582 0.001856**  **0.036582 1.2**  **Youth 13 -**  **19 years 3**  **0.038416 0.001509**  **0.039925 1.3**  **Females 13 -** **49 years 0.05**  **0.040270 0.001733**  **0.042003 84.0**  **Adults 20 -** **49 years 3**  **0.038416 0.001723**  **0.042596 1.4**  **Adults + 50 3**  **0.040873 0.001556**  **0.041826 1.4** 10

**Short -**  **a nd**  **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**  **e xposure**  **from the**  **turf use**  **is considered**  **short -** **term. T**  **he aggregate**  **MOEs from**  **food, water,**  **and residential**  **exposure are**  **1 10**  **and 2**  **26 for**  **children 1**  **- 2**  **years old**  **and the**  **US population,**  **respectively. T**  **hese MOEs**  **are greater**  **than the**  **target MOE**  **of 100**  **which indi**  **cates 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 E**  **xposure (mg/kg/day)**  **Water**

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

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

**Exposure (mg/kg/day)**  **MOE 2**  **US 100**  **0.00664 0.000048**  **0.0190 0.0257**  **226 Child 1**  **- 2 yr**  **old 100**  **0.01815 0.000072**  **0.0345 0.0527**  **110 1**  **Target MOE is 100. 2**  **Aggregate MOE = (NOA EL / (Food + Water + Residential Exposure)**  **, NOAEL = 5.8 mg/kg b.w./day.**  **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**  **ar e**  **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.**  **Ta ble 7.**  **Estimated Chronic Aggregate Exposure and Risk of Pyraclostrobin (Food and Drinkiing water)**  **Population Subgroup cPAD** 

**(mg/kg/day) Food** 

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

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

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

**cPAD U.S. Population**  **0.034 0.006635**  **0.000048 0.006683**  **19.7 All Infants (< 1 yr old)**  **0.034 0.012892**  **0.000159 0.013051**  **38.4 Children 1**  **- 2 years**  **0.034 0.018145**  **0.000072 0.018217**  **53.6 Children 3**  **- 5 years**  **0.034 0.013672**  **0.000067 0.013739**  **40.4 Children 6** 

**– 12 years**  **0.034 0.013672**  **0.000046 0.008**  **347 24.6**  **Youth 13 -**  **19 years 0.034**  **0.008301 0.000035**  **0.004912 14.4**  **Females 13 -** **49 years 0.034**  **0.005133 0.000045**  **0.005178 15.2**  **Adults 20 -** **49 years 0.034**  **0.005276 0.000045**  **0.005321 15.7** 11

**Adults + 50 0.034**  **0.005961 0.000048**  **0.006009 17.7** 

2. Non

- dietary exposure . **[ Py**  **raclostrobin is registered for use on residential and recreational turf. The applications to turf will be made only by professional**  **pest control operators. Therefore, residential handler exposure was not evaluated. The exposure assessment c** **ited in this notice of filing was transcribed from the most recent Federal Register Notice on pyraclostrobin (U.S. EPA final rule published in**  **the Federal Register October 29, 2004 [Vol 69, No. 209, p 63083**

**– 63100). The EPA**  **evaluated the following post -**  **a pplication exposure scenarios 1) adults and toddler**  **post -**  **application dermal exposure 2) toddlers’ incidental ingestion of pesticide residues on lawns form hand**  **- to**  **- mouth transfer, 3) toddlers’ object** **- to**  **- mouth**  **transfer from mouthing pesticide -** **treated turfgra ss, and 4) toddlers’ incidental**  **ingestion of soil from pesticide -** **treated residential areas. The post -**  **application exposure assessment was based on generic assumptions specified in the**  **Recommended Revisions to the Residential Standard Operating Procedures a nd**  **recommended approaches by an EPA science advisory council. 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 bec**  **ause adults and toddlers could contact treated turf immediately after application. All short** **- /intermediate term MOE 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,**  **modify, or revoke a tolerance, the Agency consider ``available information'' concerning the cumulative effects of a particular pesticide's residues and ``other**  **s ubstances that have a common mechanism of toxicity.' Pyraclostrobin is a foliar**  **fungicide which belongs to the new class of strobilurin chemistry. It is a synthetic analog of strobilurin A, a naturally occurring antifungal metabolite of the**  **mushroom Stro billurus tenacellus (Anke et. al., 1977). The active ingredient acts in**  **the fungal cell through inhibition of electron transport in the mitochondrial respiratory chain at the position of the cytochrome** **- bc1 complex. The protective**  **effect is due to the resu ltant 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**12

**The EPA is currently developing methodology to perform cumulative risk assessments. At this time, there is no available data to determine whether**  **pyraclostrobin has a co mmon mechanism of toxicity with other substances or how to**  **include this pesticide in a cumulative risk assessment. Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common**  **mechanism of toxicity, pyraclostrobin does no t appear to produce a toxic metabolite**  **common to other substances .]**  E. Safety Determination 1. U.S. population. **[ Based on this risk assessment, BASF concludes that there**  **is a reasonable certainty that no harm will result to the general population from t he**  **aggregate exposure to pyraclostrobin residues .]**  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**  **residues .]**  F. International Tolerances **[ No Codex maximum residue levels (MRLs)**  **have been established for**  **residues of pyraclostrobin. Therefore, no tolerance discrepancies exist between countries for this chemical.**  **]**