Document ID: EPA-HQ-OPP-2012-0549-0008
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2013-01-16T05:00Z

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

EPA Registration Division contact: Andrew Ertman (703)-308-9367

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. 346a(d), to amend 40 CFR
part 180 to establish new tolerances for pyraclostrobin, carbamic acid,
[2-[[[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxy]methyl]phenyl]methoxy-,
methyl ester and its metabolite methyl-N-[[[1-(4-chlorophenyl)
pyrazol-3-yl]oxy]o-tolyl] carbamate (BF 500-3); expressed as parent
compound in or on the raw agricultural commodity Artichoke, globe at 3.0
parts per million (ppm); Endive, 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, citrus,
group 10-10 at 2.0 ppm; Fruit, pome, group 11-10 at 1.5 ppm; Oilseed,
group 20 at 0.45 ppm; Caneberry subgroup 13-07A at 4.0 ppm; Bushberry
Subgroup 13-07B at 4.0 ppm; Small fruit, vine climbing subgroup (except
fuzzy kiwi) 13-07F at 2.0 ppm; and Low growing berry subgroup 13-07G at
1.2 ppm; and to amend 40 CFR part 180 by removing a tolerance for
residues of  [pyraclostrobin, carbamic acid,
[2-[[[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxy]methyl]phenyl]methoxy-,
methyl ester and its metabolite methyl-N-[[[1-(4-chlorophenyl)
pyrazol-3-yl]oxy]o-tolyl] carbamate (BF 500-3); expressed as parent
compound] in or on the raw agricultural commodity Berry, 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; Strawberry at 1.2 ppm; Vegetable, bulb, group 3
at 0.9 ppm; Vegetable, fruiting, group 8 at 1.4 ppm; Borage, seed at
0.45 ppm; Castor oil plant, seed at 0.45 ppm; Chinese tallowtree, seed
at 0.45 ppm; Crambe, seed at 0.45 ppm; Cuphea, seed at 0.45 ppm; Echium,
seed at 0.45 ppm; Euphorbia, seed at 0.45 ppm; Evening primrose, seed at
0.45 ppm; Flax seed at 0.45 ppm; Gold of pleasure, seed at 0.45 ppm;
Hare’s ear mustard, seed at 0.45 ppm, Jojoba, seed at 0.45 ppm;
Lesquerella, seed at 0.45 ppm, Lunaria, seed at 0.45 ppm; Meadowfoam,
seed at 0.45 ppm; Milkweed, seed at 0.45 ppm; Mustard, seed at 0.45 ppm;
Niger seed, seed at 0.45 ppm; Oil radish, seed at 0.45 ppm; Poppy, seed
at 0.45 ppm; Rapeseed, seed at 0.45 ppm; Rose hip, seed at 0.45 ppm;
Safflower, seed at 0.45 ppm; Sesame, seed at 0.45 ppm; Stokes aster,
seed at 0.45 ppm; Sunflower, seed at 0.45 ppm; Sweet rocket, seed at
0.45 ppm, Tallowwood, seed at 0.45 ppm, Tea oil plant, seed at 0.45 ppm,
and Vernonia, 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
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 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 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 residues in globe artichoke, globe;
endive, Blegium; and persimmon, to satisfy the requirements for a
tolerance of pyraclostrobin in these commodities.  Field trials were
carried out using the maximum proposed labeled rate, maximum proposed
number of applications, and the minimum proposed pre-harvest 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 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 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
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 developmental 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 adults 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, 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 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 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 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. 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 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 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 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 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 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 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 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, 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.

	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 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 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).  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 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 with 84.3 % 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 95th 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 years 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

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 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 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 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 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

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

Females (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 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
10=9A), Avocado, Black Sapote, Canistel, Mamey Spoted, Mango, Papaya,
Sapodilla, 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
results 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 95th 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 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 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	88.2

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.  Post application exposure from the turf use is
considered short-term.  The aggregate MOEs from food, water, and
residential exposure are 105 and 229 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. 

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

Population	Target MOE1	Food Exposure (mg/kg/day)	Water Exposure
(mg/kg/day)	Residential Exposure (mg/kg/day)	Total Exposure (mg/kg/day)
MOE2

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 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 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 clearly meet the FQPA standard of reasonable
certainty of no harm. 

  Table 7. 	Estimated Chronic Aggregate Exposure 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	0.000124	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	0.005012	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 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 cited in this notice of filing was
transcribed from the 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-application 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 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-/intermediate 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, 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 mechanism 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., 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 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 currently 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
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 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 Codex maximum residue levels (MRLs) have been established for
residues of pyraclostrobin.  Therefore, no tolerance discrepancies exist
between countries for this chemical.

 PAGE   

 PAGE   11