E PA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR
PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER

Interregional Research Project No. 4 (IR

- 4)

Petition #3E8216

EPA has received a pesticide petition ( 3E8216 ) from IR

- 4, Rutgers, The State University of New Jersey, 500 College Road East, Suite 201W, Princeton, NJ 08540 requesting, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establish ing a tolera nce for

residues of pyraclostrobin, carbamic acid, [2

- [[[1

- (4

- chlorophenyl)

- 1H

- pyrazol

- 3

- yl]oxy]methyl]phenyl]methoxy

- , methyl ester and its desmethoxy metabolite (methyl

- N

- [[[1

- (4

- chlorophenyl)

- 1H

- pyrazol

- 3

- yl]oxy]methyl] phenylcarbamate) (BF 500

- 3) ; expressed as parent compound in or on the raw agricultural commodity for H erb subgroup 19A at 85 parts per million (ppm ), dill, seed at 100 ppm and updating existing
crop groups to Fruit, stone, group 12

- 12 at 2.5 ppm and Nut, tree, group 14

- 12 at 0. 04

ppm except pistachio

. Additionally, it was proposed that upon establishment of the stone fruit group 12

- 12 and tree nut group 14

- 12 tolerances, that the existing tolerances for fruit, stone, group 12; and nut, tree, group 14 be removed as unnecessary. 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 matrices. 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 b e 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

extrac tion, 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. Magnit ude of residues. Field trials were carried out in order to determine the magnitude of the residue of pyraclostrobin (BAS 500F) in fresh chives, fresh and dry

basil , fresh dill, and dill

, seed to satisfy the requirements for a tolerance of pyraclostrobin in Herbs, subgroup 19A and dill, seed. The number and locations of field trials are in2

accordance with OPPTS Guideline 860.1500. Field trials were carried out using the maximum use rate, the maximum number of applications, and the minimum pre

- harvest

in terval. Field trials in the representative commodities for the following crop groups were previously submitted and accepted and crop group tolerances were established for Stone fruits group and Tree nuts group. This action proposes updating these crop grou ps to the current Fruit, stone, group 12

- 12 and Nut, tree, group 14

- 12 except pistachio . No new residue data was generated or needed in support of these crop group updates. No additional data were needed in support of residues in meat, milk, poultry and e ggs.

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 are proposed, an Emulsifia ble 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

. An acute neurotoxicity study in rats was conducted up to 1000 mg/kg bw/day with no evidence of neurotoxity.

2. Genotoxicity. 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 i n vivo Mouse Micronucleus test. An 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 a genotoxic hazard to humans

.

3. Reproductive and developme ntal toxicity. The reproductive and 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 adu lts or developmental toxicity in the 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, mater nal 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 teratology study, maternal toxicity observed at the mid and high doses3

consisted of decreased food consumption and body weight gain (severe at the high dose). An increased p ostimplantation 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 study in rats was also performed. Generally, mild toxicity was observed. At high dose levels in feeding stu dies, 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 ra ts. 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.

Three 28

- day studies have been performed to evaluate the ability of pyraclostrobin to affect the immune system. There were no changes observed on functional immune parameters that are considered to be adverse.

In the 28

- day repeat dose dermal study, no systemic effe cts were noted up to the highest dose tested of 250 mg/kg bw/day.

In a 28

- day inhalation study, the highest concentrations of pyraclostrobin caused effects on the nasal cavity. The NOAEC was 1 mg/m 3

.

In a 90

- day rat neurotoxicity study, a direct neurotoxic effect was not observed

.

5. Chronic toxicity. Pyraclostrobin 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 toxicity were o bserved 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 observed were an increase in 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 t o 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 dieta ry 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 a ccompanying decrease in food efficiency was observed at the high4

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 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 Age ncy 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 pyraclostr obin 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 hours. Excretion via bile was significant accou nting 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 or sulfate also occurred. In summary, pyraclo strobin 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 t oxicology 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 a s 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

.

8. Endocrine disrup tion

. 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 Ex posure 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 asse ssment was performed using the Dietary Exposure5

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 establi shed tolerances and the commodities proposed in this submission for tolerances as follows: herb, subgroup 19A , dill, seed . In addition tolerances for the following recently established groups or subgroups were used as follows: fruit, stone, group 12

- 12 an d nut, tree, group 14

- 12 except pistachio . 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 Assessment 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)

and to lerance values established since that date. 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 done 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 0.45 was used for all oilseed including 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 HAFT values were used for basil fresh (16.1 ppm), bas il dry (80.6 ppm), and dill weed (19.0), and the proposed tolerance of 85 ppm was used for all other fresh and dry herbs in subgroup 19A , and dill, seed

.

The resulting exposure estimates were compared against the pyraclostrobin (BAS 500 F) acute Populati on 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 85.1 % utilization of the

aPAD. The results of th e 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 0.043221 1.44

All Infants (< 1 year old) 0.056011 1.87

Children (1

- 2 years old) 0.080437 2.68

Children (3

- 5 years old) 0.073036 2.43

Children (6

- 12 years old) 0.042344 1.41

Youth (13

- 19 years old) 0.030471 1.02

Adults (20

- 49 years old) 0.039798 1.33

Adults (50+ years old) 0.039633 1.326

Females (13

- 49 years old) 0.042543 85.09

The results of the analysis show that for all populations, the estimated 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 i nputs for previously registered commodities were based on tolerance values, highest average field trail or average field trial residues as used in the chronic dietary assessment conducted as part of the evaluations by EPA in February 11, 2008 (DP Number 34 8308) and in April 17, 2013 (DP Number 410739). A few input values were changed from the 2008 evaluation as follows: the HAFT of 0.21 ppm was used for the subgroup 6C (except chickpea, guar and lentil at 0.34 ppm) rather than the tolerance;. Process facto rs derived from experimental studies that differed from those used in the 2008 evaluation were used as follows:, tomato juice = 0.3. Values of percent crop treated from the EPA evaluation of April 17, 2013 (DP Number 410739) were used. The highest average field trial (HAFT) residue of 16.1 ppm and 80.6 ppm measured in the residue trials was used for fresh and dry basil, respectively, and the HAFT for dry basil was used for the remaining commodities in herb subgroup 19A. The highest average field trial (HAF T) residue of 51.8 ppm was used for dill seed.

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 the 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 30.1% 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

Population Exposure Estimate % cPAD Subgroups (mg/kg b.w./day)

U.S. Population 0.002905 8.5
All Infants (< 1 year old) 0.004328 12.7

Children (1

- 2 years old) 0.010231 30.1

Children (3

- 5 years old) 0.007050 20.7

Children (6

- 12 years old) 0.003946 11.6

Youth (13

- 19 years old) 0.002061 6.1

Adults (20

- 49 years old) 0.002387 7.0

Adults (50+ years old) 0.002262 6.7

Females (13

- 49 years old) 0.002170 6.47

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 values, 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. Acute 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 1 9A), Avocado, Black Sapote, Canistel, Mamey Spoted, Mango, Papaya, Sa podilla, 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 current 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 μg/L (ppb) in surface water. The analysis was performed using DEEM

- FCID software version 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 resul ts of the acute dietary assessment 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
Subgroups (mg/kg b.w./day)

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

Adults (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 μg/L (ppb) in surface water. The analysis was performed using DEEM

- FCID software version 3.14 with the residue8

concentration in water set at 0.0023 mg/L based on the surface water concentration

determined for the nurse ry 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 t han 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 Estimate % 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 FQPA standard of reasonable certainty of no harm.

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) % aPAD

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 0.031882 1.1

Youth 13

- 19 years 0.030026 0.001617 0.041086 1.4

Females 13

- 49 years 0.042158 0.001937 0.044095 88.29

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. Post application exposure from the turf use is considered short

- term. The aggregate MOEs from food, water, and residential exposure are 10 9 an d 22 8 for children 1

- 2 years old and the US population, respectively. These MOEs are greater than the target MOE of 100 which indicates there is no safety concern. The results of the analysis are shown in Table 6. The Dermal exposure is from use on resi dential turf. The oral exposure is from food, drinking water and oral exposure from residential turf use (hand to mouth) for children 1

- 2 years of age.

Table 6. Estimated Short/Intermediate Term Aggregate Exposure and Risk of Pyraclostrobin (Food, Drinking Water, and Residential exposure)

Population Target

MOE 1 Oral Exposure (mg/kg/day) Oral MOE Dermal

E xposure (mg/kg/day) Dermal

MOE Aggregate

MOE 2

US 100 0.002953 1693 0.019 263 22 8

Child 1

- 2 yr

old 100 0.01510 384 0.03 3 152 109

1 Target MOE is 100.

2 Aggregate MOE = 1 /[(1/MOE dermal) + (1/MOE oral)]

, Oral NOAEL = 5.8 mg/kg b.w./day , Dermal NOAEL = 5.0 mg/kg b.w./day

.

Chronic Aggregate Exposure and Risk (food and water) The aggregate chronic risk includes residues of pyraclost robin from food and water (Table 7). Exposures from residential uses are not included in the chronic aggregate assessment. The results demonstrate there are no safety concerns for any subpopulation based on established and new uses, and that the results c learly meet the FQPA standard of reasonable certainty of no harm.

Table 7. Estimated Chronic 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) % cPAD

U.S. Population 0.006239 0.000048 0.006287 18.5 All Infants (< 1 yr old) 0.011203 0.000124 0.011327 33.310

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 0.005012 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 turf, gardens, and professional turf.

and recreational turf. The use on residential turf results in the highest exposure to

children 1

- 2 and adults. The exposure assessment cited in this notice of filing is from the EPA most recent evaluation using the new residential SOPs (May 8, 2013 )

. All short

- /intermediate term MOEs were greater than 100 which indicates that exposure from all

residential scena rios 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

substances that have a common mec hanism of toxicity.' Pyraclostrobin is a foliar fungicide which belongs 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., 1 977). 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 resultant death of the fungal cells by d isorganization 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 tu be growth and penetration into the host tissues. 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 assessment. 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. population. Based o n 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.11

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 Code x maximum residue levels (MRLs) have been established for residues of pyraclostrobin in fresh herbs or dill seed. Therefore, no tolerance discrepancies exist

between countries for this chemical.