UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

     OFFICE OF

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date: 09/07/2007

MEMORANDUM

SUBJECT:	Revised Pyraclostrobin: Human Health Risk Assessment for
Proposed Uses on Cotton and Belgian Endive. PC Code: 099100, Petition
Nos.: 5F7002 and 5E7014.  DP Number 343700.

		Regulatory Action: Registration Action New Section 3 Uses

		Risk Assessment Type: Single Chemical Aggregate

FROM:	Barry O’Keefe, Risk Assessor/Senior Biologist

		Registration Action Branch 3

		Health Effects Division (7509P)

THROUGH:	Paula Deschamp, Branch Chief

		Registration Action Branch 3

		Health Effects Division (7509P)

TO:	Barbara Madden, Team Leader

		Minor Use, Inerts and Emergency Response Branch (MUIERB)

		Registration Division (RD) (7505P)

			AND

	John Bazuin/Tony Kish, PM Team 22

		Fungicide Branch

		Registration Division (RD) (7505P)

This memorandum amends the recently completed HED risk assessment
document D326207, by B. O’Keefe, dated 06/25/07, i.e.,
“Pyraclostrobin: Human Health Risk Assessment for Proposed Uses on
Cotton and Belgian Endive. PC Code: 099100, Petition Nos.: 5F7002 and
5E7014.  DP Numbers 326207 and 327899.”   The recently completed risk
assessment document did not include intermediate-term aggregate risk
calculations and characterization.  However, these omissions do not
alter the risk findings expressed in the document.  While both short-
and intermediate-term exposures may occur during postapplication
activities for adults and children, the document only presented
short-term aggregate risk calculations for children 1-2 years of age.
However, additional risk calculations for intermediate-term exposures
are not needed, because the toxicity endpoints and points of departure
are identical for short- and intermediate-term exposures.  The omitted
short-/intermediate-term aggregate risk calculations for adults have now
been computed and included in this revised risk assessment document.

BASF Corporation submitted a petition (5F7002) for the establishment of
permanent tolerances 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) pyrazol-3-yl]oxy]o-tolyl] carbamate),
expressed as parent compound, in/on cotton, undelinted seed and cotton,
gin byproducts.  The petition also requested to increase the tolerance
on berries, group 13.

The Interregional Research Project No. 4 (IR-4) submitted a petition
(5E7014) for the establishment of a permanent tolerance 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) pyrazol-3-yl]oxy]o-tolyl] carbamate),
expressed as parent compound, in/on Belgian endive.

A summary of the findings and an assessment of human risk resulting from
the registered and proposed tolerances for pyraclostrobin are provided
in this document.  The risk assessment was provided by Barry O’Keefe
(RAB3), the residue chemistry data review by Jerry Stokes (RRB4), the
dietary risk assessment by Leung Cheng (RAB3), the hazard
characterization by Ghazi Dannan (RAB3), and the
occupational/residential exposure assessment by Jack Arthur (RAB3).

Note: Several deficiencies were noted in the subject petition (5E7014)
that preclude establishing a permanent tolerance for pyraclostrobin on
the proposed commodity Belgian endive.  Most importantly, the
application method used in the field residue trials does not agree with
the proposed use pattern, and the residue data generated from these
trials therefore do not support the proposed tolerance.  However, the
estimated risk from occupational exposure is not of concern.

Table of Contents

  TOC \f  1.0	Executive Summary	  PAGEREF _Toc176937523 \h  5

2.0	Ingredient Profile	  PAGEREF _Toc176937524 \h  11

2.1	Summary of Registered/Proposed Uses	  PAGEREF _Toc176937525 \h  11

2.2	Physical and Chemical Properties	  PAGEREF _Toc176937526 \h  11

3.0	Hazard Characterization/Assessment	  PAGEREF _Toc176937527 \h  14

3.1	Hazard and Dose-Response Characterization	  PAGEREF _Toc176937528 \h
 14

3.1.1	Database Summary	  PAGEREF _Toc176937529 \h  14

<IP_ADDRESS>	Studies available and considered (animal, human, general
literature)	  PAGEREF _Toc176937530 \h  14

<IP_ADDRESS>	Mode of action, metabolism, toxicokinetic data	  PAGEREF
_Toc176937531 \h  14

<IP_ADDRESS>	Sufficiency of studies/data	  PAGEREF _Toc176937532 \h  15

3.1.2	Toxicological Effects	  PAGEREF _Toc176937533 \h  16

3.1.3	Dose-response	  PAGEREF _Toc176937534 \h  18

3.2	FQPA Considerations	  PAGEREF _Toc176937535 \h  19

3.2.1	Adequacy of the Toxicity Database	  PAGEREF _Toc176937536 \h  20

3.2.2	Evidence of Neurotoxicity	  PAGEREF _Toc176937537 \h  20

3.2.3	Developmental Toxicity Studies	  PAGEREF _Toc176937538 \h  20

3.2.4	Reproductive Toxicity Study	  PAGEREF _Toc176937539 \h  21

3.3	Safety Factor for Infants and Children	  PAGEREF _Toc176937540 \h
21

3.4	Hazard Identification and Toxicity Endpoint Selection	  PAGEREF
_Toc176937541 \h  22

3.4.1    Acute Reference Dose (aRfD) - Females age 13-49	  PAGEREF
_Toc176937542 \h  23

3.4.2	Acute Reference Dose (aRfD) - General Population	  PAGEREF
_Toc176937543 \h  24

3.4.3	Chronic Reference Dose (cRfD)	  PAGEREF _Toc176937544 \h  25

3.4.4	Incidental Oral Exposure (Short- and Intermediate-Term)	  PAGEREF
_Toc176937545 \h  26

3.4.5	Dermal Absorption	  PAGEREF _Toc176937546 \h  27

3.4.6	Dermal Exposure (Short- and Intermediate-Term)	  PAGEREF
_Toc176937547 \h  28

3.4.7	Dermal Exposure (Long-Term)	  PAGEREF _Toc176937548 \h  29

3.4.8	Inhalation Exposure (Short-, Intermediate- and Long-Term)
PAGEREF _Toc176937549 \h  29

3.4.9	Level of Concern for Margin of Exposure	  PAGEREF _Toc176937550 \h
 31

3.4.10	Recommendation for Aggregate Exposure Risk Assessments	  PAGEREF
_Toc176937551 \h  32

3.4.11	Classification of Carcinogenic Potential	  PAGEREF _Toc176937552
\h  32

3.4.12	Summary of Toxicological Doses and Endpoints for Pyraclostrobin
for Use in Human Risk Assessments	  PAGEREF _Toc176937553 \h  32

3.5	Endocrine disruption	  PAGEREF _Toc176937554 \h  36

4.0	Dietary Exposure/Risk Characterization	  PAGEREF _Toc176937555 \h
36

4.1  Pesticide Metabolism and Environmental Degradation	  PAGEREF
_Toc176937556 \h  37

4.1.1	Metabolism in Primary Crops	  PAGEREF _Toc176937557 \h  37

4.1.2	Metabolism in Livestock	  PAGEREF _Toc176937558 \h  37

4.1.3	Analytical Methodology	  PAGEREF _Toc176937559 \h  37

4.1.4	Storage Stability Data	  PAGEREF _Toc176937560 \h  38

4.1.5	Magnitude of the Residue in Plants	  PAGEREF _Toc176937561 \h  39

4.1.6	Magnitude of the Residue in Processed Food/Feed	  PAGEREF
_Toc176937562 \h  44

4.1.7	Magnitude of the Residue in Meat, Milk, Poultry, and Eggs
PAGEREF _Toc176937563 \h  44

4.1.8	Confined and Field Accumulation in Rotational Crops	  PAGEREF
_Toc176937564 \h  47

4.1.9	Drinking Water Residue Profile	  PAGEREF _Toc176937565 \h  47

4.1.10	Proposed Tolerances	  PAGEREF _Toc176937566 \h  48

4.2  Dietary Exposure and Risk	  PAGEREF _Toc176937567 \h  49

4.3 Anticipated Residue and Percent Crop Treated (%CT) Information
PAGEREF _Toc176937568 \h  54

5.0	Residential (Non-Occupational) Exposure/Risk Characterization
PAGEREF _Toc176937569 \h  54

6.0	Aggregate Risk Assessments and Risk Characterization	  PAGEREF
_Toc176937570 \h  55

7.0	Cumulative Risk Characterization/Assessment	  PAGEREF _Toc176937571
\h  56

8.0	Occupational Exposure/Risk Pathway	  PAGEREF _Toc176937572 \h  56

8.1	Short-/Intermediate-Term Handler Risk	  PAGEREF _Toc176937573 \h  57

8.2	Short-/Intermediate-/Long-Term Postapplication Risk	  PAGEREF
_Toc176937574 \h  61

9.0	Data Needs and Label Requirements	  PAGEREF _Toc176937575 \h  66

9.1	Residue Chemistry Data Needs and Label Recommendations	  PAGEREF
_Toc176937576 \h  66

9.2	Occupational and Residential Exposure	  PAGEREF _Toc176937577 \h  67

10.0	Tolerance Summary	  PAGEREF _Toc176937578 \h  67

11.0	Appendix: Toxicity Profile	  PAGEREF _Toc176937579 \h  70

11.1	Appendix 1.: Pyraclostrobin Toxicology Requirements and Available
Studies for Food Uses	  PAGEREF _Toc176937580 \h  70

11.2	Appendix 2.: Acute Toxicity Data on Pyraclostrobin Technical
PAGEREF _Toc176937581 \h  71

11.3	Appendix 3.: Subchronic, Chronic and Other Toxicity Profile
PAGEREF _Toc176937582 \h  72

 1.0	Executive Summary  TC \l1 "1.0	Executive Summary

Pyraclostrobin [carbamic acid,
[2-[[[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxy]methyl] phenyl]methoxy-,
methyl ester] (CAS nomenclature) belongs to the strobilurin class of
fungicides (β-methoxyacrylate class of compounds).  Strobilurins are
synthetic analogs of a natural antifungal substance which inhibit spore
germination, mycelial growth, and sporulation of the fungus on the leaf
surface.

Pyraclostrobin is currently registered on barley, berries, Brassica
vegetables, bulb vegetables, citrus, corn (field, pop and sweet),
cucurbit vegetables, fruiting vegetables, grapes, grass grown for seed,
hops, leafy vegetables, legumes (dried peas and beans, succulent shelled
peas and beans), mint, peanuts, pistachios, pome fruit, potatoes, root
vegetables, rye, soybean, strawberries, stone fruits, sugar beets,
sunflower, tuberous and corm vegetables, tree nuts, and wheat, as well
as residential and golf course turf.  The formulated end use products
evaluated in this assessment are labeled under the trade names
Headline® (EPA Reg. No. 7969-186), Cabrio® EG (EPA Reg. No. 7969-187),
and Insignia® (EPA Reg. No. 7969-184).

Petitions were submitted by BASF Corporation (5F7002) and IR-4 (5E7014)
requesting new Section 3 registrations for use on cotton and Belgian
endive, respectively.  BASF Corporation has additionally submitted
applications for amended Section 3 registrations of pyraclostrobin on
berries, group 13 to increase the tolerance from 1.3 ppm to 4 ppm.  The
Health Effects Division (HED) has conducted a human health risk
assessment for these proposed and changed uses.  HED has high confidence
in the quality of the toxicology, chemistry and exposure databases used
to assess risk from pyraclostrobin.

An emulsifiable concentrate product (Headline® containing 23.6% ai) is
proposed for foliar application on cotton at use rates ranging from 0.1
to 0.2 lb ai/A, at intervals of 7 to 14 days.

For Belgian endive treatment, a water dispersible granule product,
Pristine® is proposed.  Pristine® contains 12.8% pyraclostrobin and
25.2% boscalid, (which is not evaluated in this assessment).  Chicory
roots, from which the endive is induced to grow, are treated by an
overhead spray bar as the roots pass underneath on a conveyor belt
headed for cold storage bins at a rate of 0.01 lb ai/850 lb roots.  Also
possible, by label instruction, is the treatment of the roots after cold
storage, at the beginning of the “forcing” stage at a rate of 0.003
lb ai/10 ft2 of forcing trays.

Hazard Assessment and Dose Response

Overall, the quality of the toxicology database for pyraclostrobin is
good and the confidence in the hazard and dose-response assessments is
high.  Pyraclostrobin has a low to moderate acute toxicity.  The main
target organs for pyraclostrobin are the upper gastrointestinal tract
(mainly the duodenum and stomach), the spleen/hematopoiesis, the immune
system, and the liver.  In reproductive and developmental studies, there
was evidence of increased qualitative susceptibility following in utero
exposure in the rabbit, but not in rats.  In the two-generation
reproduction study, the highest dose tested did not cause maternal
systemic toxicity, nor did it elicit reproductive or offspring toxicity.
 Nonetheless, HED determined that, when evaluated with the findings of
the dose-range finding one-generation reproduction study (MRID#
45596210), there is no need to repeat the two-generation reproduction
study.  In both the acute and subchronic neurotoxicity studies, there
were no indications of treatment-related neurotoxicity.

This risk assessment is an update of the last human health risk
assessment (dated November 30, 2005, DP Barcode no. D323632) and it
includes an updated toxicology and hazard evaluation.  The update
includes results of recently submitted toxicity studies, a new
carcinogenicity evaluation, and selection of new study/endpoints for
exposure by the inhalation route.

The new toxicology studies include a supplemental carcinogenicity study
in female Wistar mice (MRID 46678201), a 28-day inhalation toxicity
study in Wistar rats (MRID 46638801), and a bacterial reverse-mutation
assay (MRID 45921201).  Both animal toxicity studies were carried out to
fulfill the toxicology data needs that were specified in an earlier risk
assessment (Section 10.1 of human risk assessment, dated August 27,
2004, DP Barcode no. D290342). The mutation assay tested pyraclostrobin
(technical) from the production plant with the complete profile of
impurities as described in BASF’s letter to the Agency dated April 10,
2003.

Inhalation exposure risk assessments:  In this risk assessment, the
occupational and residential inhalation exposure risk scenarios are
updated using the new route specific guideline acceptable 28-day
inhalation study with NOAEL/LOAEL of 0.23/6.92 mg/kg/day (0.001/0.03
mg/L air) based on adverse histopathology findings in the duodenum and
the respiratory system including duodenal mucosal hyperplasia, lung
alveolar histiocytosis, and olfactory atrophy/necrosis in the nasal
tissue.

  SEQ CHAPTER \h \r 1 Carcinogenicity:  The recent CARC reevaluation
concluded that, in accordance with the EPA’s Final Guidelines for
Carcinogen Risk Assessment (March, 2005), pyraclostrobin should be
classified into the category “Not Likely to be Carcinogenic to
Humans” based on no treatment-related increase in tumors in both sexes
of rats and mice, which were tested at doses that were adequate to
assess carcinogenicity, and the lack of evidence of mutagenicity.  The
CARC concluded that quantification of carcinogenic potential is not
required (TXR document no. 0054516, dated 2/15/07).  This decision
supersedes   SEQ CHAPTER \h \r 1 the previous decision to use the no
observable adverse effects level (NOAEL) for females from the mouse
carcinogenicity study (>33 mg/kg/day) to calculate cancer margins of
exposure (MOEs).

Drinking Water Exposure Estimates

The Environmental Fate and Effects Division (EFED) concluded that the
use rates for the proposed uses are much lower than the use rate on
turf, the crop that was previously selected for the drinking water
assessment.  Therefore, the estimated concentrations of pyraclostrobin
in drinking water associated with the last Section 3 request remain
valid.

A Tier 2 surface drinking water assessment was performed using PRZM
3.12/ EXAMS 2.7.97 modeling with index reservoir (IR) scenarios and
percent cropped area (PCA) adjustment factors.  Concentrations of
pyraclostrobin in surface water are not likely to exceed 10.2 µg/L for
the peak concentration, 0.8 µg/L for the annual average concentration,
and 0.5 µg/L for the 30 year average concentration.

The SCI-GROW model predicts the acute and chronic concentrations of
pyraclostrobin in shallow ground water to be 0.02 ppb.  Ground water
sources were not included in the dietary assessment, as the estimated
drinking water concentrations (EDWCs) for this water source are minimal
in comparison to surface water.

Dietary Exposure Assessment

Acute and chronic dietary exposure assessments were conducted for the
proposed and existing food uses and drinking water inputs.  These acute
and chronic dietary risk assessments are considered only minimally
refined.

The acute analysis was conducted using either tolerance level residues
or highest residues derived from field trial data conducted at the
maximum application rate and minimum PHI permitted on the proposed or
existing labels.  For all commodities 100% crop treated was assumed.  A
limited number of experimentally derived processing factors were used to
refine the acute analysis.  Of note is that relative contribution from
drinking water is minimal.  HED concludes that the acute exposure
estimates are unlikely to underestimate actual acute exposure.

The chronic dietary assessment was conducted using tolerance level
residues for all crops except for apple, grape, head lettuce, leaf
lettuce, celery, spinach, orange, pepper and tomato where average
residue values were derived from crop field trials.  These field trials
represent maximum application rates and minimum PHIs.  For all
commodities 100% crop treated was assumed.  A limited number of
experimentally derived processing factors were used to refine the
analysis.  Again, the relative contribution from drinking water is
minimal.  HED concludes that the chronic exposure estimates in this
analysis are unlikely to underestimate actual exposure.

Acute and chronic exposures and risks do not exceed HED’s level of
concern for the U.S. population and for all relevant population
subgroups.  At the 95th percentile, the acute dietary exposure utilized
1.4% of the aPAD for the general U.S. population and 78% of the aPAD for
females 13-49 years old, the most highly exposed population subgroup.
The chronic dietary exposure utilized 19% of the cPAD for the general
U.S. population and 48% of the cPAD for children 1-2 years old, the most
highly exposed population subgroup.

Aggregate Exposure Assessment

There are existing residential uses on turf which must be aggregated
with food and drinking water exposures.  Postapplication short- and
intermediate-term dermal and incidental oral exposures are expected to
occur from the turf use pattern.  Common effects (i.e., decreased body
weight gain, food intake, and food efficiency) were seen in the studies
selected to evaluate dietary, dermal and incidental oral ingestion
exposures; and therefore, route-specific exposures can be aggregated.

Aggregate assessments are required for acute and chronic dietary (food +
drinking water) exposures.  These aggregate assessments are covered in
the dietary section of this executive summary.  Additionally, short- and
intermediate-term aggregate risk assessments are required.  Both short-
and intermediate-term exposures may occur during postapplication
activities for adults and children.  However, because the toxicity
endpoints and points of departure are identical for short- and
intermediate-term exposures, separate risk estimates for short- and
intermediate-term exposures were not calculated.  These
short-/intermediate-term aggregate risk assessments take into account
average exposure estimates from dietary consumption of pyraclostrobin
(food and drinking water) and non-occupational/residential uses (turf);
i.e. for kids incidental oral, dermal, and average food plus drinking
water exposures are aggregated, and for adults, dermal and average food
plus drinking water exposures are aggregated.

The total combined MOE from dietary (food + water) and
non-occupational/residential exposure is 100 for children 1-2 years old,
which is not of concern to HED.  For adults the total combined MOE is
170, which also is not of concern to HED.  These aggregate exposure risk
assessments are considered conservative estimates, that should not
underestimate risks, because of the following inputs: 1) dietary inputs
primarily used tolerance level residues; 2) crop specific (turf)
screening level drinking water modeling data were used (i.e., Tier II
surface water model); 3) maximum application rates and minimum
application intervals were used; and 4) conservative SOPs and upper
level estimates of exposure were employed.

Occupational Handler Exposure Assessment

Cotton

For the foliar use on cotton, handlers may experience
short-/intermediate-term exposure to pyraclostrobin while mixing/loading
and applying sprays.  No chemical-specific handler exposure data were
submitted in support of this use pattern, therefore, data from the
Pesticide Handlers Exposure Database (PHED) Version 1.1 as presented in
the PHED Surrogate Exposure Guide (8/98) were used.  The results of the
occupational handler exposure and risk assessment for cotton indicate
that risks are not of concern (MOEs > 100) with baseline clothing, or in
some cases, when gloves and a respirator are used to mitigate exposure.

Belgian endive

For the use on Belgian endive, the exposure to handlers is from mixing
and loading.  Application is mechanical, and therefore, no applicator
exposure is expected.  MOEs for handlers supporting postharvest
applications to Belgian endive roots (actually chicory roots) are all
much larger than 100 with workers wearing only baseline clothing, and
therefore, are not of concern to HED.

Occupational Postapplication Exposure Assessment

Cotton

From foliar applications to cotton postapplication exposure is possible
for workers entering treated fields.  Chemical-specific dislodgeable
foliar residue (DFR) data had previously been submitted by the
registrant to support earlier registration requests for food crops.  The
DFR data were used to estimate restricted entry intervals (REIs) by
extrapolating, where possible, to cotton.  It was found that the type of
formulation used influences the DFR profile; therefore, only DFR values
for the emulsifiable concentrate formulation (i.e., the Headline®
fungicide formulation) were considered.  The results of the
postapplication exposure and risk assessment indicate that MOEs of 100
are achieved on Day 0 for all cotton scenarios and, therefore, are not
of concern.

The pyraclostrobin technical material has been classified in Toxicity
Category III for acute dermal, primary eye irritation, and primary skin
irritation.  Per the Worker Protection Standard (WPS), a 12-hr
restricted entry interval (REI) is required for chemicals classified
under Toxicity Category III or IV.

Belgian endive

HED has determined that there is potential exposure to persons handling
Belgian endive roots after post-harvest application is complete.  No
chemical-specific data were submitted to assess the postapplication
exposure to Belgian endive roots treated with pyraclostrobin.
Therefore, HED used surrogate data and default assumptions.

As a worse-case post-application exposure scenario, HED assessed the
long-term dermal exposure of workers hand-packing individual treated
roots into forcing trays.  This exposure was assessed for long-term
duration, because the operation occurs on a continuous basis throughout
the entire year.  The estimated exposure/risk is considered high end
because it is based on the assumption that contact with roots occurs on
the same day as treatment.  In reality, the pyraclostrobin residue on
the roots is likely to have dissipated by some percentage over the week
to 12 months between treatment and when the packing activity actually
occurs.

The estimated long-term postapplication dermal exposure/risk to workers
handling Belgian endive roots treated with pyraclostrobin results in an
MOE of 60.  Because the level of concern is for MOEs <100, this risk is
of concern to HED.  However, because exposure from the assessed activity
is primarily to the hands, the addition of chemical-resistant gloves
should reduce exposure by 90%, resulting in a MOE = 610; which is not of
concern to HED.  This latter activity is viewed by HED as a secondary
“handler” activity, and therefore the label should include the
aforementioned glove requirements.

Recommendations

No deficiencies were noted in the subject petition (5F7002) that would
preclude establishing permanent tolerances for pyraclostrobin on the
proposed cotton commodities.  HED  SEQ CHAPTER \h \r 1  recommends
establishing permanent tolerances for pyraclostrobin at 0.3 ppm in/on
undelinted cottonseed, and at 30 ppm in/on cotton gin byproducts.  The
additional berry data also support increasing the current tolerance on
the berries crop group from 1.3 to 4.0 ppm.

Several deficiencies were noted in the subject petition (5E7014) that
preclude establishing a permanent tolerance for pyraclostrobin on the
proposed commodity Belgian endive.  Most importantly, the application
method used in the field residue trials does not represent the proposed
use pattern, and the residue data generated from these trials therefore
do not support the proposed tolerance.

For the proposed use on Belgian endive the following are needed if IR4
chooses to pursue a Section 3 registration:

Use directions in Section B must match the application method used in
Section D for residue data collection;

The tolerance proposal in Section F must be supported by the application
method used in Section D for residue data collection;

Additional residue data that adequately reflect the use directions in
Section B must be submitted (HED recommends that the petitioner submit a
protocol for HED review and comment before any residue data collection
begins.); and

The label should include a requirement for chemical-resistant gloves.

For the proposed use on Belgian endive, HED recommends that the label
rate be revised to clearly define the amounts to be used per application
and the total per season.  In addition, the petitioner should define how
the spray is applied to the roots in the forcing trays (i.e., trays are
stationary or are moving on a conveyor belt).  A revised Section B must
be submitted to adequately reflect the petitioner’s intentions as to
application rates and directions.  Refer to section 9.1 for details.

As a condition of registration, HED previously required the registrant
to conduct three additional field trials in Zones 2, 3, and 10 to
support the group tolerance on Brassica, leafy greens, subgroup 5B.
These data have been submitted and reviewed, and satisfy the outstanding
condition of registration data requirement for additional field trial
data.

Environmental Justice Considerations

Potential areas of environmental justice concerns, to the extent
possible, were considered in this human health risk assessment, in
accordance with U.S. Executive Order 12898, "Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations,"   HYPERLINK
"http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf"
http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf ).

As a part of every pesticide risk assessment, OPP considers a large
variety of consumer subgroups according to well-established procedures.
In line with OPP policy, HED estimates risks to population subgroups
from pesticide exposures that are based on patterns of that subgroup’s
food and water consumption, and activities in and around the home that
involve pesticide use in a residential setting.  Extensive data on food
consumption patterns are compiled by the USDA under the Continuing
Survey of Food Intake by Individuals (CSFII) and are used in pesticide
risk assessments for all registered food uses of a pesticide.  These
data are analyzed and categorized by subgroups based on age, season of
the year, ethnic group, and region of the country.  Additionally, OPP is
able to assess dietary exposure to smaller, specialized subgroups and
exposure assessments are performed when conditions or circumstances
warrant.  Whenever appropriate, non-dietary exposures based on home use
of pesticide products and associated risks for adult applicators and for
toddlers, youths, and adults entering or playing on treated areas
postapplication are evaluated.  Further considerations are currently in
development as OPP has committed resources and expertise to the
development of specialized software and models that consider exposure to
bystanders and farm workers as well as lifestyle and traditional dietary
patterns among specific subgroups.

Review of Human Research

This risk assessment does not rely on any data from studies in which
human subjects were intentionally exposed to a pesticide or other
chemical.

2.0	Ingredient Profile  TC \l1 "2.0	Ingredient Profile

2.1	Summary of Registered/Proposed Uses  TC \l2 "2.1	Summary of
Registered/Proposed Uses

Pyraclostrobin is currently registered on barley, berries, Brassica
vegetables, bulb vegetables, citrus, corn (field, pop and sweet),
cucurbit vegetables, fruiting vegetables, grapes, grass grown for seed,
hops, leafy vegetables, legumes (dried peas and beans, succulent shelled
peas and beans), mint, peanuts, pistachios, pome fruit, potatoes, root
vegetables, rye, soybean, strawberries, stone fruits, sugar beets,
sunflower, tuberous and corm vegetables, tree nuts, and wheat, as well
as residential and golf course turf.  The proposed uses evaluated in
this assessment are summarized in Table 1.

Table 1.  Summary of Proposed Use Pattern for Cotton and Belgian Endive

Product (formulation)	Use Site	Max. Single Application Rate	Max.
Applications per Season	PHI	Application Method/Instructions

Headline® fungicide

(EC 23.6% ai)

Cotton

0.2 lb ai/acre

3

30	Groundboom sprayers and aerial application Applications should begin
prior to disease development and continue throughout the season at 7- to
14-day intervals.

Pristine® fungicide (WDG 12.8% ai)

Belgian Endive	0.01 lb ai/850 lb roots (cold storage)

1 prior to cold storage

Not specified	Applied by overhead, shielded spray bars (T-Jets)as
commodity moves along on conveyor belt.

200,000 lbs roots handled per day

0.003 lb ai/10 ft2 of forcing tray (forcing)

1 prior to forcing

Applied by overhead, shielded spray bars (T-Jets)as commodity moves
along on conveyor belt.

2000 ft2 of forcing trays handled per day

2.2	Physical and Chemical Properties  TC \l2 "2.2	Physical and Chemical
Properties

Common Name:	Pyraclostrobin

IUPAC

Nomenclature:	methyl
N-{2-[1-(4-chlorophenyl)-1H-pyrazol-3-yloxymethyl]phenyl}(N-methoxy)carb
amate

CAS

Nomenclature:	methyl
[2-[[[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxy]methyl]phenyl]methoxycarbam
ate

CAS Number:	175013-18-0

Chemical Class/Type:	β-methoxyacrylate (compound class) / Strobilurin
(fungicide class)

Mode of Action:	Acts at the cellular level by inhibiting electron
transport in the mitochondrial respiratory chain at the cytochrome-bc1
complex; this disrupts the energy producing systems and can lead to the
breakdown of the mitochondrial and cytoplasmic membranes.

Impurities

of Concern:	The technical grade pyraclostrobin does not contain any
impurities or microcontaminants of concern.

Molecular Formula:	C19H18ClN3O4

Molecular Weight:	387.82

Appearance:	White to light beige solid

Melting Point:	63.7 - 65.2(C

Boiling Point:	N/A

Density:	1.285 g/cm3 at 20(C

Water Solubility:	2.41 mg/L in deionized water at 20(C

1.9 mg/L in buffer system pH 7 at 20(C

2.3 mg/L in buffer system pH 4 at 20(C

1.9 mg/L in buffer system pH 9 at 20(C

Solvent Solubility:	at 20(C in:  acetone ((160 mg/L); methanol (11
mg/L); 2-propanol (3.1 mg/L); ethyl acetate ((160 mg/L); acetonitrile
((76 mg/L); dichloromethane ((110 mg/L); toluene ((100 mg/L); n-heptane
(0.36 mg/L); 1-octanol (2.4 mg/L); olive oil (2.9 mg/L); DMF ((62 mg/L).

Vapor Pressure:	2.6 x 10-10 hPa  (at 20(C); 6.4 x 10-10 hPa  (at 25(C)

pKa:			Does not dissociate in water.  There are no dissociable moieties.

Kow:	n-Octanol/water partition coefficient (Kow) at room temperature
(=Kow of 3.80, pH 6.2; =log Kow 4.18, pH 6.5).

3.0	Hazard Characterization/Assessment  TC \l1 "3.0	Hazard
Characterization/Assessment

The most recent risk assessment was supported by hazard endpoint
conclusions in the HIARC report (TXR 0051553, dated 2/10/03) and the
carcinogenicity assessment in the CARC memo dated 10/22/03 (TXR No.
0051445).  Since then, new toxicology studies have been made available,
including a supplemental female mouse carcinogenicity study and a 28-day
rat inhalation study.  This hazard characterization includes results of
these new toxicity studies, a new carcinogenicity evaluation, and
selection of new endpoints for exposure by the inhalation route based on
the findings in the 28-day rat inhalation study.

3.1	Hazard and Dose-Response Characterization  TC \l2 "3.1	Hazard and
Dose-Response Characterization

3.1.1	Database Summary  TC \l3 "3.1.1	Database Summary

<IP_ADDRESS>	Studies available and considered (animal, human, general
literature)  TC \l4 "<IP_ADDRESS>	Studies available and considered (animal,
human, general literature)

Acute- oral, dermal, inhalation, eye irritation, skin irritation, dermal
sensitization

Subchronic- Dermal 28-day rat; inhalation 28-day rat, oral 28-day rat,
oral 90-day rat, oral 90-day mouse, oral 90-day dog;

Chronic- Oral rat and oral dog;

Carcinogenicity – Rat and mouse;

Reproductive/developmental- Oral prenatal developmental rat, oral
prenatal developmental rabbit, 2-generation reproductive rat;

Other- Mutagenicity screens, and metabolism and pharmacokinetic studies;
acute and subchronic neurotoxicity studies; and dermal penetration
study.

<IP_ADDRESS>	Mode of action, metabolism, toxicokinetic data  TC \l4 "<IP_ADDRESS>
Mode of action, metabolism, toxicokinetic data

  SEQ CHAPTER \h \r 1 Pyraclostrobin [carbamic acid,
[2-[[[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxy]methyl] phenyl]methoxy-,
methyl ester] (CAS nomenclature) belongs to the strobilurin class of
fungicides.  Other strobilurin fungicides include azoxystrobin,
kresoxim-methyl, trifloxystrobin, fluoxastrobin, and picoxystrobin.
Strobilurins are synthetic analogs of a natural antifungal substance
(basidiomycete antibiotics) which inhibit spore germination, mycelial
growth, and sporulation of the fungus on the leaf surface.

  SEQ CHAPTER \h \r 1 The biochemical mode of action of strobilurins
consists of interaction with the ubiquinone binding site of the
mitochondrial bc1 complex (complex III) in fungal cells, thereby
preventing the oxidation of ubihydroquinone and the transfer of
electrons to cytochrome c. Interrupting the electron transport chain in
this way prevents oxidative phosphorylation, thus causing a severe
reduction in the availability of ATP, the main energy currency of the
cell. The shortage of energy has a very wide range of biochemical
consequences, such as the breakdown of essential membrane potentials and
concentration gradients and the inhibition of nucleic acid and protein
biosynthesis. Fungal spore germination, mycelial growth and the
development of infection structures are thus prevented.

-1 hours and 8 hours (two peaks); males had lower plasma concentrations
than females (↓16-38%) during the earlier time points.  Elimination
was biphasic at the low dose with plasma half-lives of nearly 10 and 35
hours and monophasic at the high dose with a half-life of nearly 20
hours.  The distribution patterns of radioactivity in tissues were
similar between sexes (typically higher among females) reaching peak
levels at 0.5 hours post-dosing; some of the highest concentrations were
found in the liver, thyroid, kidney, lung, adrenal glands, and pancreas.
There was no evidence of tissue accumulation since levels at 42-72 hours
dropped greater than 20-fold relative to the earliest measurement at 0.5
hour.  Nearly 33 metabolites were isolated and identified in the urine,
feces, and bile; there were no sex- or dose-related differences in the
metabolite profile in urine or feces but the position of the label
seemed to alter the profile, particularly in the urine.  The metabolic
pathway included phase-I reactions such as N-demethoxylation, various
hydroxylations, and cleavage of the ether bond with subsequent
oxidation; these were followed by the phase II glucuronidation and
sulfation reactions.

<IP_ADDRESS>	Sufficiency of studies/data  TC \l4 "<IP_ADDRESS>	Sufficiency of
studies/data

  SEQ CHAPTER \h \r 1 The available studies provide sufficient
information to determine whether and to what extent pyraclostrobin may
pose a human health hazard (see Appendices 2-3 for acute and repeated
dose studies/findings).  Acute and chronic reference doses for dietary
risks as well as doses for non-dietary risks are based on guideline
acceptable studies with well-characterized endpoints and NOAEL/LOAEL
values.  The available studies have been thoroughly evaluated for
guideline acceptability by individual reviewers and peer-review
committees and, despite inadequate dosing in some of the studies, the
database is considered sufficient to characterize and quantify risk.

This risk assessment also incorporates new toxicity studies that have
been made available recently since the previous human health risk
assessment (dated 11/30/05, DP Barcode No. D323632).  These include a
supplemental carcinogenicity study in female Wistar mice (MRID
46678201), a 28-day inhalation toxicity study in Wistar rats (MRID
46638801), and a bacterial reverse-mutation assay (MRID 45921201).  Both
animal toxicity studies were carried out to fulfill the toxicology data
needs that were specified in an earlier risk assessment (Section 10.1 of
human risk assessment dated 8/27/04, DP Barcode no. D290342). The
mutation assay tested pyraclostrobin (technical) from the production
plant with the complete profile of impurities as described in BASF’s
letter to the Agency dated 4/10/03.  An almost identical previous
mutation study (MRID 45118332) tested pyraclostrobin (technical) from
the pilot plant.

3.1.2	Toxicological Effects  TC \l3 "3.1.2	Toxicological Effects

The toxicity profile of pyraclostrobin, including acute toxicities, may
be found in Appendices 2 and 3.

  SEQ CHAPTER \h \r 1 Acute Toxicity:  Pyraclostrobin has a low to
moderate acute toxicity based on its classification in Toxicity Category
IV via the oral route, Toxicity Category III by the dermal route, and
Toxicity Category II by the inhalation route of exposure.
Pyraclostrobin produces moderate eye irritation (Toxicity Category III),
is a moderate dermal irritant (Toxicity Category III), and is not a
dermal sensitizer (Appendix 1).

Toxicity from Repeated Oral Exposure: Based on findings in repeated
dosing oral studies in more than one species, the main target organs for
pyraclostrobin are the upper gastrointestinal tract (mainly the duodenum
and stomach), the spleen/hematopoietic system, the liver, and the immune
system (listed in the order from most to least sensitive).  In addition,
reduced body weight/gain and feed intake/efficiency are also common
findings.  In the 90-day dietary rat, mouse, and dog feeding studies,
one or more of the following gastrointestinal (GI) changes were noted:
thickening of the duodenal wall, duodenum mucosal hypertrophy or
hyperplasia, as well as gross and microscopic ulceration/erosion in the
glandular stomach.  Mucosal hyperplasia in the duodenum was also
observed in rats of both sexes after 28-day administration of 500
(42.3/46.6 (M/F) mg/kg/day) and 1500 (120.2/126.3 (M/F) mg/kg/day) ppm
pyraclostrobin.  The upper GI-tract effects might, at least partly,
explain some of the adverse effects on food consumption/utilization, and
body weight; all these effects had a similar threshold which was lower
than that needed to elicit the other toxic responses.

The liver was a target organ in the 28-day rat and the 90-day rat and
mouse dietary feeding studies based on slight to moderate increased
relative liver weight in both species and hepatocellular hypertrophy in
the rat studies.  Liver necrosis was also increased in the two-year rat
carcinogenicity study.

hils, and lymphocytes.  In mice, there was mild hemolytic anemia
accompanied by a large decline (≥50%) in leukocytes (leukopenia),
neutrophils, and lymphocytes.  The large decline in white blood cell
(WBC) populations was accompanied by dose-dependent thymus atrophy and
increased lymph node apoptosis.  The incidences of thymus atrophy ranged
from 3/10 to 8/10 in each of the top four dose groups of both sexes
compared to 0/10 in the control and lowest dose groups; the severity
also increased dose-dependently.

Reproductive & Developmental Toxicity: The pre- and post-natal
toxicology database for pyraclostrobin include the rat and rabbit
developmental toxicity studies and the two-generation reproduction
toxicity study in rats.  There was no evidence of increased quantitative
or qualitative susceptibility following in utero exposure to rats.  The
developmental findings of increased incidences of dilated renal pelvis
and cervical ribs with no cartilage were seen at a higher dose than that
which caused maternal toxicity and these findings were within historical
control background incidences; therefore, they are considered
developmental variations rather than malformations.  In the rabbit
developmental toxicity study, there was evidence of qualitative
susceptibility; increases in resorptions/litter and post-implantation
losses were seen in the presence of maternal toxicity (decreases in body
weight gain and food consumption).  However, the concern is low for the
qualitative susceptibility in the rabbit developmental study because:
The developmental effects were seen in the presence of maternal
toxicity; there are clear NOAELs for maternal and developmental
toxicities; and this endpoint is used for the acute dietary (RfD) for
Females+ 13 as well as for short- and intermediate-term dermal risk
assessments.

In the two-generation study, there were no adverse maternal systemic
toxicity other than a marginal (non-adverse) decrease (<= 5%) in F0 and
F1 parental body weights at the high dose of 300 ppm.  The F1 and F2
pups of the 300 ppm dose group had slight decreases in body weights
during lactation which were explained to be “likely due to the fact
that pups start eating food at this time (day 7) along with potentially
receiving test compound or its metabolites in mother milk.”  The
findings were not considered adverse in part because of almost total
body weight recovery in F1 parental animals during premating, gestation,
and lactation.  The NOAEL/LOAEL were 300/>300 ppm for parental,
reproductive, and offspring toxicities.   In the one generation study,
the NOAEL/LOAEL were <200/<= 200 ppm based on dose-dependent decrease in
F1 pup body weights.

The HIARC decided that, when evaluated with the findings of the
dose-range one-generation reproduction study, there is no need to repeat
the two-generation reproduction study (document dated 2/10/03, TXR no.
0051553).  The HIARC noted that the greater body weight/body weight gain
sensitivity in the offspring of the one-generation reproduction study is
possibly due to decreased feed intake by treated pups as they start
eating solid feed around day 14; this effect was not reproduced in the
two-generation toxicity study.

It should be noted that there was some overlap in the magnitude of the
body weight decrease in F1 pups at 300 ppm (4-10%), 200 ppm (7-14%), and
400 ppm (11-20%) to the extent possible from two completely different
and independent studies.  For any end-point, some degree of variation is
to be expected between control animals from different studies for
different reasons including animal husbandry (e.g., diurnal, seasonal)
as well as differences in instruments and people who collect the
measurements.  This inter-study variation may explain the F1 pup body
weight variance and lack of a perfect dose-response among the similar
dose levels (300 ppm vs. 200 and 400 ppm) in both studies.

  SEQ CHAPTER \h \r 1 In conclusion, athough no toxicity was seen at 300
ppm (29.0 mg/kg/day) in the two-generation reproduction study, a new
study is not required since such a study would be conducted using a much
higher dose and would not provide any additional data for risk
assessment purposes.  The concern with that study is not that it did not
test at a low enough dose but the opposite.  Further, it should be noted
that acute and chronic reference doses for dietary risks as well as
doses for non-dietary risks are based on other studies with NOAELs below
the high dose in the two generation study.

Neurotoxicity: In both the acute and subchronic neurotoxicity studies,
there were no indications of treatment-related neurotoxicity including
clinical signs, qualitative or quantitative neurobehavioral effects,
brain weight, or gross/microscopic pathology.  None of the other
guideline studies reported treatment-related effects on any of these
parameters.  However, there was a large decrease (about 50%) in serum
cholinesterase (but not in erythrocyte or brain cholinesterases) among
the females in the rat 28- and 90-day dietary studies at relatively
large doses (1000/1500 ppm or about 80 - 126 mg/kg/day).  This response
might require exposure to a relatively high dose since serum
cholinesterase (ChE) was not affected at the end of the two-year chronic
toxicity feeding study in rats including the top dose of 200 ppm
(9.2/12.6 mg/kg/day in males/females).  Also, pyraclostrobin does not
seem to persist in rat tissues (see following section) which might
explain why serum ChE is not affected by a lifetime exposure to a
relatively low dose but is depressed following a short-term exposure at
a high dose.

Carcinogenicity:  In the Report of the Cancer Assessment Review
Committee (CARC) dated October 22, 2003, pyraclostrobin was classified
as “data are inadequate to assess the human carcinogenic potential”
based on the determination of inadequate dose levels in the
carcinogenicity study for female mice only (TXR No. 0051445).  In
consultation with the HED Dose Adequacy Review Team (DART), BASF
corporation initiated a supplemental carcinogenicity study in female
mice using one dose group (360 ppm) and a control (n=50 animals/group).
In the meantime, HED used a regulatory Margin of Exposure (MOE) as a
tool for bounding any potential chronic dietary cancer risk from
pyraclostrobin as explained in the previous risk assessments (DP
Barcodes D290342 and D323632 dated 8/27/04 and 11/30/05).  The
regulatory MOE was derived from the highest dose tested in female mice
(32.8 mg/kg/day) in the inadequate mouse oncogenicity study and was 10X
higher than the NOAEL used for chronic non-cancer risk assessment.

Due to excessive body weight decrease in the treated group, BASF
requested and received permission from HED DART to terminate the
supplemental study well before its intended 18 months duration.  With
the termination of the supplemental carcinogenicity study in female mice
(MRID 46678201), the CARC reevaluated the carcinogenicity potential of
pyraclostrobin.  In accordance with the EPA’s Final Guidelines for
Carcinogen Risk Assessment (March, 2005), the CARC classified
pyraclostrobin into the category “Not Likely to be Carcinogenic to
Humans” based on no treatment-related increase in tumors in both sexes
of rats and mice, which were tested at doses that were adequate to
assess carcinogenicity, and the lack of evidence of mutagenicity.  The
CARC concluded that quantification of carcinogenic potential is not
required (TXR document no. 0054516, dated 2/15/07).  Therefore, the
above described regulatory MOE approach is no longer needed.

3.1.3	Dose-response  TC \l3 "3.1.3	Dose-response

 A variety of oral toxicity studies were used for the different risk
assessment scenarios including the rabbit developmental toxicity study,
the acute neurotoxicity study in rats, the rat carcinogenicity study,
and the 13-week study in dogs.  In addition, the 28-day inhalation study
in rats will now be used for short- and intermediate-term occupational
and residential inhalation risk assessments.  The endpoints in these
studies are well characterized and are the most sensitive among
available comparable toxicity studies in other species.  All dietary
endpoints (i.e., acute and chronic RfDs), are calculated from the
respective study’s NOAEL after applying a 100-fold safety factor (10 X
to account for interspecies extrapolation and 10X for intraspecies
variation).  For all other scenarios, including dermal, inhalation, and
incidental oral, an MOE approach will be used with a Level of Concern
(LOC) at 100.

The selected endpoint from the acute neurotoxicity study of 300
mg/kg/day for the acute dietary (general population) risk assessment is
appropriate because the decreased body weight gain in males occurred
during the first week after a single oral high dose of 1000 mg/kg.

The rabbit developmental toxicity study findings are used for endpoint
selections for acute dietary (Females 13+) as well as for short- and
intermediate-term dermal exposures.  For the acute dietary endpoint
(Females 13+), the rabbit developmental findings of increased
resorptions/post-implantation loss at the LOAEL of 10 mg/kg/day are
assumed to occur following a single in utero exposure.  These effects
were dose-dependently increased at the next (high) dose of 20 mg/kg/day.
The same study and developmental endpoint are used for short- and
intermediate-term dermal exposures after applying a dermal absorption
factor of 14%.  Additionally, the maternal endpoints of decreased body
weight gain and decreased food intake and food efficiency were found at
the LOAEL of 10 mg/kg/day.  This selection mitigates any concern from
the observed developmental toxicity findings in rabbits which are not
assessed in the rat dermal toxicity study.

The rat carcinogenicity study findings are used for endpoint selections
for chronic dietary and dermal exposures based on findings of decreased
body weight/gain and kidney tubular casts/atrophy in both sexes in
addition to liver necrosis and stomach lesions in males at the high dose
(LOAEL) of 9.2 mg/kg/day.  This study has the lowest NOAEL (3.4
mg/kg/day) in the most sensitive species following chronic exposure.
The dermal absorption factors of 14% will be applied to the dermal
long-term risk scenario.

The short-, intermediate-, and long-term inhalation exposures will be
based on the new 28-day inhalation toxicity study in rats which had
dose-dependent adverse findings in the respiratory system and duodenum.
The study’s oral equivalents NOAEL/LOAEL are 0.23/6.92 mg/kg/day
(corresponding to study’s air concentration of 0.001/0.03 mg/L air).
The findings are well characterized in that the severity, frequency, and
location (e.g., along the respiratory tract) are dose-dependent ranging
from no effects at the NOAEL of 0.001 mg/L air to severe respiratory
effects and death at the highest dose of 0.3 mg/L air.

3.2	FQPA Considerations  TC \l2 "3.2	FQPA Considerations

3.2.1	Adequacy of the Toxicity Database  TC \l3 "3.2.1	Adequacy of the
Toxicity Database

The toxicity data base for pyraclostrobin is adequate for evaluation of
the FQPA safety factor.  The following acceptable studies are available:

	Developmental toxicity studies in rats and rabbits

	Two-generation reproduction study in rats

3.2.2	Evidence of Neurotoxicity  TC \l3 "3.2.2	Evidence of Neurotoxicity

In all studies, including the acute and subchronic guideline acceptable
neurotoxicity studies, there were no signs of neurotoxicity or
neuropathology.    SEQ CHAPTER \h \r 1 Serum cholinesterase (ChE)
activity was decreased (by 41-56%) in females (80 and 119 mg/kg/day) in
the 90-day rat study and among the 126 mg/kg/day females in the 28-day
rat study.  On the other hand, erythrocyte ChE in the 28- and 90-day rat
studies and brain ChE in the 28-day were all unchanged.  However, this
response might require a relatively high dose since serum ChE was not
affected at the end of the two-year chronic toxicity feeding study in
rats (MRID 45118329) including the top dose of 9.2/12.6 mg/kg/day in
males/females.  In the acute and subchronic toxicity studies, there were
no physiological or behavioral effects to corroborate the serum ChE
inhibition seen in female rats.    SEQ CHAPTER \h \r 1 Based on the
weight of evidence presented, the HIARC concluded that a developmental
neurotoxicity study is not required for pyraclostrobin.

3.2.3	Developmental Toxicity Studies  TC \l3 "3.2.3	Developmental
Toxicity Studies

As discussed above, there is no evidence of increased quantitative or
qualitative susceptibility following in utero exposure to rats.  The rat
developmental findings of increased incidences of dilated renal pelvis
and cervical ribs with no cartilage were seen at a higher dose than that
which caused maternal toxicity and these findings were within historical
control background incidences; therefore, they are considered
developmental variations rather than malformations.

  SEQ CHAPTER \h \r 1 As discussed above and in the HIARC report (dated
2/10/03, TXR No. 0051553), the concern is low for the qualitative
susceptibility seen in the rabbit developmental study and there are no
residual uncertainties because: The developmental effects were seen in
the presence of maternal toxicity; there are clear NOAELs for maternal
and developmental toxicities; and this endpoint is used for risk
assessment.

The findings in the two- and one-generation toxicity studies and
susceptibility issues were discussed earlier (3.1.2).  It was concluded
that the concern is low for the quantitative susceptibility seen in the
one-generation reproduction study and there are no residual
uncertainties because: The offspring effects seen in this study were not
repeated in the two generation study; the marginal decrease in pup
weights seen at or after PND-7 may be due to higher exposure via their
diet; and the dose (NOAEL 3.4 mg/kg/day) used for the chronic RfD risk
assessment would address the effects of concern seen in the offspring.
Although no toxicity was seen at 300 ppm (29.0 mg/kg/day) in the
two-generation reproduction study, a new study is not required since
such a study would be conducted using a much higher dose and would not
provide any additional data for risk assessment purposes.

  SEQ CHAPTER \h \r 1 In both the acute and subchronic neurotoxicity
studies, there were no indications of treatment-related neurotoxicity
including clinical signs, qualitative or quantitative neurobehavioral
effects, brain weight, or gross/microscopic pathology.  None of the
other guideline studies reported treatment-related effects on any of
these parameters.

3.2.4	Reproductive Toxicity Study  TC \l3 "3.2.4	Reproductive Toxicity
Study

As discussed above, there is no evidence of increased quantitative or
qualitative susceptibility following in utero exposure to rats.  Also,
the concern is low for the qualitative susceptibility seen in the rabbit
developmental study and there are no residual uncertainties because: The
developmental effects were seen in the presence of maternal toxicity;
there are clear NOAELs for maternal and developmental toxicities; and
this endpoint is used for risk assessment.

As discussed above, the concern is low for the quantitative
susceptibility seen in the one-generation reproduction study and there
are no residual uncertainties because: The offspring effects seen in
this study were not repeated in the two generation study; the marginal
decrease in pup weights seen at or after PND-7 may be due to higher
exposure via their diet; and the dose (NOAEL 3.4 mg/kg/day) used for the
chronic RfD risk assessment would address the effects of concern seen in
the offspring.  Although no toxicity was seen at 300 ppm (29.0
mg/kg/day) in the two-generation reproduction study, a new study is not
required since such a study would be conducted using a much higher dose
and would not provide any additional data for risk assessment purposes.

3.3	FQPA Safety Factor for Infants and Children  TC \l2 "3.3	Safety
Factor for Infants and Children

This assessment reaffirms previous conclusions that the 10X FQPA safety
factor for the protection of infants and children should be removed for
all potential exposure scenarios to pyraclostrobin because the database
is complete and adequate and there are no residual uncertainties for
pre- and/or postnatal toxicity.  The doses chosen as quantitative risk
estimates are adequately protective for infants and children.  Exposure
data are complete or are estimated based on data that reasonably account
for potential exposures.

The acute dietary analysis was based on tolerance level or highest
residues and 100% crop treated assumptions for all commodities.
Experimentally derived processing factors were used for fruit juices and
tomato and wheat commodities.  The contribution from drinking water is
minimal.  HED concludes that the acute exposure estimates in this
analysis are unlikely to underestimate actual exposure.

The chronic dietary analysis included tolerance level or average
residues from field trial data and 100% crop treated assumptions for all
commodities.  A limited number of experimentally derived processing
factors were used for fruit juices and tomato and wheat commodities.
The field trials represent maximum application rates and minimum PHIs.
The contribution from drinking water is minimal.  HED concludes that the
chronic exposure estimates in this analysis are unlikely to
underestimate actual exposure.

The dietary drinking water assessment utilizes water concentration
values generated by model and associated modeling parameters which are
designed to provide conservative, health protective, high-end estimates
of water concentrations which will not likely be exceeded.

While there is potential for postapplication residential exposure, the
best data and approaches currently available were used in the
pyraclostrobin residential assessment.  The Agency used the current
conservative approaches for residential assessment, many of which
include recent upgrades to the SOPs.  The Agency believes that the
calculated risks represent conservative estimates of exposure because
maximum application rates are used to define residue levels upon which
the calculations are based.  Exposures are unlikely to be under
estimated because the assessment was a screening level assessment.

Based on these data and conclusions, the FQPA Safety Factor can be
reduced to 1X.

3.4	Hazard Identification and Toxicity Endpoint Selection  TC \l2 "3.4
Hazard Identification and Toxicity Endpoint Selection

The previous pyraclostrobin risk assessments utilized toxicity studies
via the oral route to perform risk assessments for occupational and
residential inhalation exposure scenarios.   In this assessment, the
inhalation exposure risk scenarios have been updated using the guideline
acceptable 28-day inhalation study.  The study’s executive summary and
a summary of the route-to-route extrapolation to convert an inhalation
concentration (mg/L) to an oral equivalent dose (mg/kg) are provided in
section 3.4.8 and in Appendix 3.  For short- and intermediate-term
inhalation exposures, the earlier risk assessments selected the NOAEL of
5.0 mg/kg/day from the oral prenatal developmental toxicity study in
rabbits based on developmental toxicity findings of increased
resorptions.  A 100% inhalation absorption factor was used to convert
all inhalation exposures to an oral equivalent dose.    SEQ CHAPTER \h
\r 1 For long-term inhalation exposures, the NOAEL of 3.4 mg/kg/day from
the oral rat carcinogenicity study was selected; however, long-term
exposures are not expected to occur.  Herein, the NOAEL of 0.23
mg/kg/day (equivalent to 0.001 mg/L air) from the 28-day inhalation
study will be used for short- and intermediate-term residential and
occupational inhalation risk assessments.  This NOAEL is based on
duodenum mucosal hyperplasia and adverse respiratory system
histopathology findings including alveolar histiocytosis and olfactory
atrophy/necrosis in nasal tissue at 6.92 mg/kg/day (equivalent to 0.03
mg/L air).  The same study and endpoint will also be used for long-term
residential and occupational inhalation scenarios even though long-term
exposures are not likely at this time.  For long-term inhalation
exposure scenarios, the level of concern for MOE will be retained at
100, i.e., it will not be increased to account for using the short-term
study for the long-term scenario.  This decision is supported by the
large NOAEL/LOAEL dose spread (30-fold) and the fact that additional and
more severe toxicity findings were seen at the top dose which is only
10-fold higher than the LOAEL.

With the exception of inhalation endpoints and the new point of
departure for cancer, all endpoints that were selected in the previous
human health risk assessments remain valid.  As discussed above (under
3.1.2), the 28-day rat inhalation toxicity study will be used in this
risk assessment for all durations of residential and occupational
inhalation scenarios.

3.4.1    Acute Reference Dose (aRfD) - Females age 13-49  TC \l3 "3.4.1
  Acute Reference Dose (aRfD) - Females age 13-49

Study Selected: Rabbit Prenatal Developmental Toxicity			§870.3700

MRID No.: 45118326/45437001

Executive Summary: In a prenatal developmental toxicity study
(Teratology) (MRID# 45118326), sexually mature, virgin Chbb:HM (outbred
strain) Himalayan rabbits (Supplier: BOEHRINGER INGELHEIM PHARMA KG)
received either 0, 5, 10, or 20 mg/kg/day BAS 500 F (Purity: 98.9%;
Batch No.: CP028719) in 0.5% Tylose CB 30.000 (in doubly distilled
water) by oral gavage from days 7 through 28 post ingestion (p.i.),
inclusive.  A check was made twice daily on working days or once daily
(Saturday, Sunday or on public holidays) (days 0 - 29 p.i.).  The
maternal animals were examined for clinical symptoms with all animals
weighed on days 0, 2, 4, 7, 9, 11, 14, 16, 19, 21, 23, 25, 28 and 29
p.i. along with consumption of food determined daily during the entire
study period.  On day 29 p.i., the surviving dams were sacrificed and
the fetuses were removed from the uterus, the dams were then necropsied
and assessed by gross pathology, the uterus and the ovaries were removed
and weighed with the number of corpora lutea, the number and
distribution of implantation sites recorded.  The fetuses were examined
for external, visceral and skeletal anomalies.

No treatment related mortality was noted.  Reduced fecal output was seen
in 1 mid dose (day 10 p.i.) and 10 high-dose animals (days 10-14 p.i.).
Two mid-dose and 4 high-dose animals showed blood in the bedding
(between days 16-29 p.i.).  No other relevant clinical observations were
noted.  All treated groups had lower body weight gains during the dosing
period (days 7-28) and the overall gestation period (day 0-29) while the
mid and high dose groups had lower body weight gains during the post
dosing period (days 28-29).  The decreased body weight gain, among all
treated groups, can mainly be attributed to the earliest post-treatment
period, namely gestation days 7-9 (treatment days 0-2). As seen with the
body weights and body weight gains, all treated groups had reduced food
consumption during the treatment period (days 7-28), and the overall
gestation period (days 0-29).  Food efficiency was lower in all treated
groups during the same periods as food consumption and during the post
dosing period (days 28-29).  No treatment related pathological
observations were noted in the data provided.  There was reduced litter
size, increased resorptions per dam and increased post implantation loss
in the high dose group.  Maternal toxicity was further evaluated in
another study (MRID 45437001, review in Appendix I) and no significant
maternal toxicity was observed a 1, 3, or 5 mg/kg/day.  Therefore when
these two studies are used together, they support a Maternal Toxicity
NOAEL of 5 mg/kg/day.  The maternal toxicity NOAEL was 5 mg/kg/day and
the maternal toxicity LOAEL was 10 mg/kg/day based on body weight gains,
reduced food consumption and reduced food efficiency.

There was increased resorptions per dam, increased post implantation
loss and a dose related increase in dams with total resorptions in the
mid and high dose groups. There was also an increased incidence of the
anomaly: lumbar vertebrae absent in the high dose group as well as
reduced litter size.  The developmental toxicity NOAEL was 5 mg/kg/day
and the developmental toxicity LOAEL was 10 mg/kg/day based on increased
resorptions per litter, increased post-implantation loss and dams with
total resorptions.

This study is classified as Acceptable-Guideline and satisfies the
guideline requirements (§ 83-3a) for a Prenatal Developmental Toxicity
Study (Teratology) in rabbits.

Dose and Endpoint for Establishing aRfD: Developmental Toxicity NOAEL of
5.0 mg/kg/day based on increased resorptions/litter and increased total
resorptions (i.e., dams with complete litter loss).

Uncertainty Factor (UF):	100

Comments about Study/Endpoint/Uncertainty Factor: The developmental
effects are presumed to occur following a single exposure of females of
child-bearing age and, therefore, are appropriate for this risk
assessment.

	Acute RfD (Females 13-50) = 	   5.0  mg/kg (NOAEL)   = 	0.05  mg/kg

							100 (UF)

3.4.2	Acute Reference Dose (aRfD) - General Population  TC \l3 "3.4.2
Acute Reference Dose (aRfD) - General Population

  SEQ CHAPTER \h \r 1 Study Selected:  Rat Acute Oral Neurotoxicity
§870.6100

MRID No.: 45118337

eral nervous system tissues.  The Systemic Toxicity LOAEL for males was
1000 mg/kg bw based on 33% decreased body weight gain (p ≤ 0.01) on
days 0-7; no similar effect was detected on days 0-14.  The Systemic
Toxicity NOAEL was 300 mg/kg bw.  The Systemic Toxicity LOAEL for
females could not be determined since there were no adverse,
treatment-related effects noted at any dose level tested.  The Systemic
Toxicity NOAEL for females was 1000 mg/kg bw.  The Neurotoxicity LOAEL
could not be determined since there were no treatment-related neurotoxic
effects noted at any dose level tested.  The Neurotoxicity NOAEL was
1000 mg/kg bw.

This acute neurotoxicity study is classified as Acceptable/Guideline and
satisfies the guideline requirement for an acute neurotoxicity study
[OPPTS 870.6100(§81-7)] in rats.  Also note that the highest dose
tested was 1000 mg/kg and not 2000 mg/kg as suggested by the guidelines.
 However, this deficiency is not considered serious enough to render the
study unacceptable because there were no changes in any of the
neurotoxicity indices up to the highest tested dose.

Dose and Endpoint for Establishing RfD: The systemic toxicity NOAEL of
300 mg/kg based on decreased body weight gain in males at 1000 mg/kg.

Uncertainty Factor (UF):	100

Comments about Study/Endpoint/Uncertainty Factor: The decreased body
weight gain was seen after a single oral dose during the first week
after exposure and therefore is appropriate for the exposure scenario.

	Acute RfD (General Population) =     300 mg/kg (NOAEL)   = 	3.0	mg/kg

							100 (UF)

3.4.3	Chronic Reference Dose (cRfD)   TC \l3 "3.4.3	Chronic Reference
Dose (cRfD)

  SEQ CHAPTER \h \r 1 Study Selected:  Rat Oral Carcinogenicity
Guideline #:  870.4200

MRID No.:	45118331

Note:  The tumor findings described in the executive summary below
reflect the original HED review.  Subsequently, the HED CARC evaluated
the carcinogenicity potential for pyraclostrobin.  In its most recent
evaluation, the CARC classified pyraclostrobin into the category “Not
Likely to be Carcinogenic to Humans” based on no treatment-related
increase in tumors in both sexes of rats and mice, which were tested at
doses that were adequate to assess carcinogenicity, and the lack of
evidence of mutagenicity (TXR document no. 0054516, dated 2/15/07).

Executive Summary:  In a rat carcinogenicity study (MRID 45118331),
pyraclostrobin (97.09% a.i., Lot/Batch # J.-Nr. 27882/191/c) was
administered in the diet to Wistar rats (50/sex/group) for up to 104
weeks at nominal doses of 0, 25, 75, or 200 ppm, equivalent to 0/0,
1.2/1.5, 3.4/4.7, and 9.2/12.6 mg/kg/day [M/F], respectively.

Mortality, clinical signs, food efficiency, and hematology findings for
both sexes at all doses were unaffected by treatment.  No
treatment-related findings were observed in the 25 or 75 ppm dose
groups.

In the 200 ppm group, decreased (p≤0.05 or 0.01) body weights were
observed in the males (↓3-7%) at weeks 1 through 81 and in the females
(↓4-14%) at weeks 21 through 104; body weights in the males at 104
weeks was decreased (↓4%; not statistically significant [NS]).
Decreased (p≤0.05 or 0.01) body weight gains were observed in the
males (↓6-10%) at weeks 1 through 81 and in the females (↓7-22%) at
weeks 21 through 104; cumulative body weight gain in the males at week
104 was decreased (↓5%; NS).  Decreased (p≤0.05 or 0.01) food
consumption was observed in the males (↓3-7%) sporadically during
weeks 1 to 13.  Increased (p≤ 0.05) relative kidney weights were
observed in the males (↑9%) and females (↑19%).  In addition,
increased incidences of kidney tubular casts in the males (15/50 treated
vs 5/50) and females (14/50 treated vs 10/50 controls) and kidney
tubular atrophy in the males (16/50 treated vs 5/50 controls) and
females (19/50 treated vs 12/50 controls) were observed.  In the males,
an increased incidence of necrosis of the liver was observed
microscopically (10/50 treated vs 1/50 control).  Additionally,
erosion/ulcer of the glandular stomach was observed grossly (12/50
treated vs 7/50 controls) in the males.  Microscopically, an increased
incidence of acanthosis (6/50 treated vs 0/50 controls) and ulcers (4/50
treated vs 2/50 controls) of the forestomach and ulcers (7/50 treated vs
2/50 controls) and erosion of the glandular stomach (10/50 treated vs
2/50 controls) were also observed in the males.

The LOAEL is 200 ppm for males and females (equivalent to 9.2/12.6
mg/kg/day [M/F]) based on differences in body weight and body weight
gains, increased incidences of kidney tubular casts and atrophy in males
and females, and in males, an increased incidence of necrosis of the
liver, gross and microscopic evidence of erosion/ulcer of the glandular
stomach and an increased incidence of acanthosis and ulcers of the
forestomach.  The NOAEL is 75 ppm (equivalent to 3.4/4.7 mg/kg/day
[M/F]).

The submitted study is classified as Acceptable/Guideline (§83-2[a])
and satisfies the requirements for a carcinogenicity study in rats.

Dose and Endpoint for Establishing RfD: The NOAEL of 3.4 mg/kg/day (75
ppm) based on decreased body weight and body weight gains, increased
incidences of kidney tubular casts and atrophy in males and females, and
in males, an increased incidence of liver necrosis, gross and
microscopic evidence of erosion/ulcer of the glandular stomach and an
increased incidence of acanthosis (hyperplasia) and ulcers of the
forestomach at 9.2 mg/kg/day (200 ppm).

Uncertainty Factor(s): 	100

Comments about Study/Endpoint/Uncertainty Factor:  The lowest NOAEL in
the most sensitive species following chronic exposure.

	Chronic RfD  =        3.4 mg/kg/day (NOAEL)   = 	0.034	mg/kg/day

					100 (UF)

3.4.4	Incidental Oral Exposure (Short- and Intermediate-Term)   TC \l3
"3.4.4	Incidental Oral Exposure (Short- and Intermediate-Term)

  SEQ CHAPTER \h \r 1 Study Selected:  13-Week Feeding Dog Study
§870.3150

MRID No.: 45118323

Executive Summary: In a subchronic toxicity study (MRID #45118323), BAS
500 F, purity 97.09%, was administered to 5 beagles/sex/dose in the diet
at dose levels of 0, 100, 200 and 450 ppm (equal to 0, 2.8, 5.8 and 12.9
mg/kg bw/day for males, and 0, 3.0, 6.2 and 13.6 mg/kg bw/day for
females) for a 90-day period.

No treatment-related deaths were observed at any dose level.  All
animals in the 450 ppm group vomited for the first 1 to 3 weeks, which
was considered to be a transient aversion to the test material.  In
addition, all animals in the high dose group had diarrhea throughout the
study period.  A slight increase in the incidence of diarrhea noted in
the 200 ppm group was not considered to be toxicologically significant
because of its scattered/ isolated occurrence. Decreased food intake
(-9%), a net loss in body weight (-12%) and decreased food efficiency
(-1.05% vs. 5.26% in controls) were seen in the 450 ppm group, females
only.  Clinical chemistry findings included a slight decrease at 450 ppm
in total protein, albumin, globulin (all three parameters in both sexes
ranged from -7% to -12%; only total protein was significantly different
from controls) and in glucose on days 41/43 and 90 among the 450 ppm
females (-9.4 % to -13%, p≤0.01). These findings are considered to
reflect a trend towards lower values indicative of a marginal
treatment-related effect. Gross and histopathological examination
revealed that the duodenum is a target organ in both sexes at 450 ppm as
evidenced by thickening of the duodenal wall (each sex: 2/5 vs. 0/5
controls) and mucosal hypertrophy (males: 2/5 vs. 0/5 controls and
females: 1/5 vs. 0/5 controls).

The LOAEL is 450 ppm (equal to 12.9 mg/kg bw/day for males and 13.6
mg/kg bw/day for females), based on an increased incidence of diarrhea,
clinical chemistry changes and mucosal hypertrophy of the duodenum (both
sexes) and body weight loss, decreased food intake and decreased food
efficiency (females only). The NOAEL is 200 ppm (equal to 5.8 mg/kg
bw/day for males and 6.2 mg/kg bw/day for females).

This subchronic toxicity study in the dog is acceptable and satisfies
the guideline requirement for a subchronic oral study (OPPTS 870.3150;
OECD 409) in dogs.

Dose and Endpoint for Risk Assessment:  The NOAEL of 6 mg/kg/day based
on increased incidence of diarrhea, clinical chemistry changes, duodenum
mucosal hypertrophy, and effects on body weight and food
intake/efficiency at 13 mg/kg/day (LOAEL).

Comments about Study/Endpoint:  The NOAEL/LOAEL in this study are
comparable to the maternal NOAEL/LOAEL (5/10 mg/kg/day) established in
the rabbit developmental toxicity study, and the end-point is
appropriate for the population of concern (toddlers).

3.4.5	Dermal Absorption  TC \l3 "3.4.5	Dermal Absorption

The HIARC recommended that   SEQ CHAPTER \h \r 1 a dermal penetration
rate of 14% should be used for dermal exposure risk assessments for
pyraclostrobin (2nd HIARC report dated 7/22/02, TXR No. 0050932).

3.4.6	Dermal Exposure (Short- and Intermediate-Term)   TC \l3 "3.4.6
Dermal Exposure (Short- and Intermediate-Term)

  SEQ CHAPTER \h \r 1 Study Selected:  Rabbit Prenatal Developmental
Toxicity		§870.3700

MRID No.: 45118326

Executive Summary: under above item 3.5.1

Dose/Endpoint for Risk Assessment:  Developmental Toxicity NOAEL of 5.0
mg/kg/day based on increased resorption/litter and increased total
resorptions (i.e., dams with complete litter loss) at 10 mg/kg/day
(LOAEL).

Comments about Study/Endpoint:  In its earlier meetings of July 31, 2001
and June 25, 2002, the HIARC noted that the 28-day dermal toxicity study
in rats (MRID 45118324) showed no effects at the highest tested dose of
250 mg/kg/day, which is well below the limit-dose of 1000 mg/kg/day (HED
doc. No. 014669 and TXR No. 0050932).  Therefore, it is not known if
there are systemic effects at higher doses via the dermal route; the
dermal toxicity study was, therefore, considered a data gap until it is
repeated up to the limit dose.  The HIARC selected an oral study because
of the concern for the developmental toxicity seen in the rabbits which
are not assessed in the dermal study.  Furthermore, the NOAEL/LOAEL in
the selected study are supported by the NOAEL/LOAEL of the 13-week dog
(6/13 mg/kg/day) and 1-year dog (5.4/10.8 mg/kg/day) studies.  The
dermal absorption factor of 14% should be applied to extrapolate from
the oral route to the dermal route.

In its meeting of December 17, 2003, the HIARC evaluated BASF’s
response regarding the 28-day dermal toxicity study as a data gap and
concluded that another dermal toxicity study will not be needed since an
oral end-point (developmental toxicity NOAEL of 5.0 mg/kg/day) with a
14% dermal absorption rate yield a dermal equivalent dose of 36
mg/kg/day (5 ÷ 0.14) which is well below the NOAEL of 250 mg/kg/day
established in the available study and, therefore, should address any
concerns for toxicity via the dermal route (TXR No. 0051553).

3.4.7	Dermal Exposure (Long-Term)   TC \l3 "3.4.7	Dermal Exposure
(Long-Term)

  SEQ CHAPTER \h \r 1 Study Selected:  Rat Oral Carcinogenicity
§870.4200

MRID No.:  45118331

Executive Summary:	under above item 3.5.3

Dose and Endpoint for Risk Assessment:  The NOAEL of 3.4 mg/kg/day based
on decreased body weight and body weight gains, increased incidences of
kidney tubular casts and atrophy in males and females, and in males, an
increased incidence of liver necrosis, gross and microscopic evidence of
erosion/ulcer of the glandular stomach and an increased incidence of
acanthosis (hyperplasia) and ulcers of the forestomach at 9.2 mg/kg/day.

Comments about Study/Endpoint:   This study/dose/endpoint was also used
for deriving the chronic RfD.  The dermal absorption factor of 14%
should be applied to extrapolate from the oral route to the dermal
route.

3.4.8	Inhalation Exposure (Short-, Intermediate-, and Long-Term)   TC
\l3 "3.4.8	Inhalation Exposure (Short-, Intermediate- and Long-Term)

Study Selected: 28-Day rat inhalation

MRID No.:  46638801

EXECUTIVE SUMMARY:  In a subchronic inhalation toxicity study (MRID
46638801), Pyraclostrobin (BAS 500F) technical (98.7% a.i., Batch #
LJ27882/199/b) was dissolved in acetone and administered as an aerosol
to 10 Wistar rats/sex/concentration by nose-head only exposure at
concentrations of 0 (air), 0 (vehicle control), 0.001, 0.030, or 0.300
mg/L for 6 hours per day, 5 days/week for 28 days (i.e., 20 exposure
days).

There were no treatment-related effects on any parameters examined
during the FOB or on locomotor activity, ophthalmoscopy, clinical
chemistry, or organ weights except for decreased thymus weight and
relative weight (27-29%) in females and increased relative spleen weight
(33%) in males of the 0.300 mg/L group.

At 0.300 mg/L, several clinical signs of toxicity were observed among
males and females during daily or weekly examinations including urine
odor, slight visually increased respiration, and piloerection in
addition to abdominal position and moderate labored respiration observed
in one male on Day 21.  Additionally, at this concentration, four males
and three females died prior to scheduled termination.  Prior to death,
these animals exhibited visually increased respiration, urine odor, and
piloerection.

At 0.300 mg/L, decreases in body weights of 4-7% (not significant [NS]
except on Day 21) and decreases in cumulative body weight gains of
43-141% (p<0.05) were noted in the males throughout the study.  Food
efficiency was decreased (p<0.05) at this concentration on Day 7 (-2.6%
treated vs. 4.0% controls) and on Day 21 (6.5% treated vs. 9.9%
controls).  Additionally on Day 21, food efficiency was decreased in the
0.030 mg/L males (5.8% treated vs. 9.9% controls).  In both sexes at
this concentration, an initial decrease of 11-13% (p<0.05) in food
consumption was observed on Day 7.

At 0.300 mg/L, absolute and relative (to body) thymus weights were
decreased (27-29%, p<0.01) in males while relative spleen weight was
increased in females (33%, p<0.01).  Minor changes were also seen in
weights of liver, kidneys, and lungs but were not considered
treatment-related.

At 0.300 mg/L, leukocytes and neutrophils were increased in both sexes.
As discussed below, the increased white blood cells (specifically
neutrophils) may be an inflammatory response to the treatment-related
effects on the respiratory tissues.

At 0.030 and 0.300 mg/L, diffuse mucosal hyperplasia of the duodenum was
observed in 5-7 males (vs. 0 controls) and in 5-10 females (vs. 1
control).  This finding increased with dose in both incidence and
severity.  The duodenum was also a target organ in the 90-day dietary
feeding studies in the rat, mouse, and dog (MRIDs 45118321, 45118320 and
45118323).

Other microscopic changes were effects on the respiratory system at
0.030 and 0.300 mg/L, including minimal to slight alveolar histiocytosis
in the females (5 treated vs 1 control) and minimal to moderate
olfactory atrophy/necrosis in nasal cavities II through IV in the males
(2-10) and females (3-9) compared to 0 controls.

Additional necropsy and microscopic findings in the respiratory system
in both sexes were noted at 0.300 mg/L including lung discoloration,
lung congestion, minimal to moderate hyperplasia of the respiratory
epithelium in nasal cavities I through IV, reactive inflammation in
nasal cavity I, slight olfactory regeneration/repair in nasal cavity IV,
minimal to slight respiratory hyperplasia in level III of the larynx
(males only), and minimal to slight squamous cell metaplasia in nasal
cavity III.

The LOAEL is 0.030 mg/L based on findings of hyperplasia in the
duodenum, alveolar histiocytosis in the lungs, and olfactory
atrophy/necrosis in the nasal tissues.  The NOAEL is 0.001 mg/L.

At the request of the Agency, this study was conducted for 28 days,
instead of the 90 days required by Guideline OPPTS 870.3465.  Aside from
the different study duration, this study was conducted in accordance
with Guideline OPPTS 870.3465.

This 28-day study is classified as acceptable/guideline and satisfies
the guideline requirement (OPPTS 870.3465; OECD 413) for a subchronic
inhalation study in the rat.

Dose and Endpoint for Risk Assessment:  Inhalation toxicity NOAEL of
0.001 mg/L (equivalent to 0.23 mg/kg/day) based on findings of duodenal
hyperplasia, lung alveolar histiocytosis, and nasal olfactory
atrophy/necrosis at 0.03 mg/L (equivalent to 6.92 mg/kg/day).

Comments on Study/Endpoint/Uncertainty Factors:  Study duration and the
endpoint are appropriate for the short or intermediate scenarios of
inhalation exposure.  As stated in the study’s executive summary, HED
concurred with the duration of 28 days, instead of the 90 days required
by Guideline OPPTS 870.3465.  The same study and endpoint will also be
used for long-term residential and occupational inhalation scenarios
even though long-term exposures are not expected at this time.  For
long-term inhalation exposure scenarios, the level of concern for MOE
will be retained at 100, i.e., it will not be increased to account for
using the short-term study for the long-term scenario.  This decision is
supported by the large NOAEL/LOAEL dose spread (30-fold) and the fact
that additional and more severe toxicity findings were seen at the top
dose which is only 10-fold higher than the LOAEL.

3.4.9	Level of Concern for Margin of Exposure  TC \l3 "3.4.9	Level of
Concern for Margin of Exposure

Table 2.  Summary of Levels of Concern for Risk Assessment.

Route	Short-Term

(1 - 30 Days)	Intermediate-Term

(1 - 6 Months)	Long-Term

(> 6 Months)

Occupational (Worker) Exposure

Dermal	100	100	100

Inhalation	100	100	100

Residential Exposure

Dermal	100	100	100

Inhalation	100	100	100

Incidental Oral	100	100	100

3.4.10	Recommendation for Aggregate Exposure Risk Assessments  TC \l3
"3.4.10	Recommendation for Aggregate Exposure Risk Assessments

As per the FQPA, when there are potential residential exposures to the
pesticide, aggregate risk assessment must consider exposures from three
major sources: oral, dermal and inhalation exposures.  When common
toxicity endpoints are selected for these routes of exposure they may be
aggregated.  Aggregate assessments are required for acute and chronic
dietary (food + water) exposures, and short-term residential exposures
(i.e., chronic dietary plus incidental oral and dermal exposures).

Residential short-/intermediate-term dermal exposure was assessed using
the NOAEL (5 mg/kg/day) from the rabbit developmental study.  While the
developmental effect of increased resorptions is not applicable to
toddlers, it should be noted that the maternal NOAEL from this study is
also 5 mg/kg/day, and is based on reduced body weight gain, food
consumption, and food efficiency at the LOAEL of 10 mg/kg/day; this more
relevant endpoint was used to assess toddler dermal exposure.  For
incidental oral ingestion, exposure was assessed using the endpoint from
a 13-week feeding study in the dog.  The NOAEL from this study is 5.8
mg/kg/day, based on increased incidence of diarrhea, clinical chemistry
changes, duodenum mucosal hypertrophy, and decreased body weight and
food intake/efficiency at the LOAEL of 12.9 mg/kg/day.  A common effect
(i.e., decreased body weight gain, food intake, and food efficiency) was
seen in the studies selected to evaluate toddler dermal and incidental
oral ingestion exposure; therefore, route-specific MOEs were aggregated
for toddlers.

3.4.11	Classification of Carcinogenic Potential  TC \l3 "3.4.11
Classification of Carcinogenic Potential

With the termination of the supplemental carcinogenicity study in female
mice (MRID 46678201), the CARC reevaluated the carcinogenicity potential
of pyraclostrobin.  In accordance with the EPA’s Final Guidelines for
Carcinogen Risk Assessment (March, 2005), the CARC classified
pyraclostrobin into the category “Not Likely to be Carcinogenic to
Humans” based on no treatment-related increase in tumors in both sexes
of rats and mice, which were tested at doses that were adequate to
assess carcinogenicity, and the lack of evidence of mutagenicity.  The
CARC concluded that quantification of carcinogenic potential is not
required (TXR document no. 0054516, dated 2/15/07.

3.4.12	Summary of Toxicological Doses and Endpoints for Pyraclostrobin
for Use in Human Risk Assessments  TC \l3 "3.4.12	Summary of
Toxicological Doses and Endpoints for Pyraclostrobin for Use in Human
Risk Assessments

With the exception of inhalation and carcinogenicity risk assessments,
all previous exposure risk assessments remain unchanged.  Below are the
updated tables.

Table 3. Summary of Toxicological Doses and Endpoints for Pyraclostrobin
for Use in Dietary and Non-Occupational Human Health Risk Assessments

Exposure/

Scenario	Point of Departure	Uncertainty/FQPA Safety Factors	RfD, PAD,
Level of Concern for Risk Assessment	Study and Toxicological Effects

Acute Dietary (General Population, including Infants and Children)
NOAEL= 300 mg/kg/day	UFA= 10x

UFH= 10x

FQPA SF= 1x

	Acute RfD = 3.0 mg/kg/day

aPAD = 3.0 mg/kg/day	Rat Acute Oral Neurotoxicity

LOAEL = 1000 mg/kg/day based on decreased body weight gain in males.

Acute Dietary

(Females 13-49 years of age)	NOAEL = 5.0 mg/kg/day	UFA= 10x

UFH= 10x

FQPA SF= 1x 	Acute RfD = 0.05 mg/kg/day

aPAD = 0.05 mg/kg/day	Rabbit Prenatal Developmental Toxicity

LOAEL = 10.0 mg/kg/day based on developmental toxicity findings of
increased resorptions.  SEQ CHAPTER \h \r 1

Chronic Dietary (All Populations)	NOAEL= 3.4 mg/kg/day	UFA= 10x

UFH= 10x

FQPA SF= 1x

	Chronic RfD = 0.034 mg/kg/day

cPAD = 0.034 mg/kg/day	  SEQ CHAPTER \h \r 1 Rat Oral Carcinogenicity

LOAEL = 9.2 mg/kg/day based on decreased body weight/body weight gain,
kidney tubular casts and atrophy in both sexes; increased incidence of
liver necrosis and erosion/ulceration of the glandular- stomach and
fore-stomach in males.

Incidental Oral Short-Term (1-30 days)	NOAEL= 5.8 mg/kg/day	UFA= 10x

UFH= 10x

FQPA SF= 1x

	Residential LOC for MOE = 100	  SEQ CHAPTER \h \r 1 13-Week Feeding Dog
Study

LOAEL = 12.9 mg/kg/day based on increased incidence of diarrhea,
clinical chemistry changes, duodenum mucosal hypertrophy, and decreased
body weight and food intake/efficiency.

Incidental Oral Intermediate-Term (1-6 months)	NOAEL= 5.8 mg/kg/day	UFA=
10x

UFH= 10x

FQPA SF= 1x

	Residential LOC for MOE = 100	  SEQ CHAPTER \h \r 1 13-Week Feeding Dog
Study

LOAEL = 12.9 mg/kg/day based on increased incidence of diarrhea,
clinical chemistry changes, duodenum mucosal hypertrophy, and decreased
body weight and food intake/efficiency.

Dermal Short-Term (1-30 days)	Oral study NOAEL = 5.0 mg/kg/day

  SEQ CHAPTER \h \r 1 (dermal absorption rate = 14 %)	UFA= 10x

UFH= 10x

FQPA SF= 1x	Residential LOC for MOE = 100

	Rabbit Prenatal Developmental Toxicity

LOAEL = 10.0 mg/kg/day based on developmental toxicity findings of
increased resorptions and maternal toxicity based on decreased body
weight gain and decreased food intake/efficiency.

Dermal Intermediate-Term (1-6 months)	Oral study NOAEL = 5.0 mg/kg/day

  SEQ CHAPTER \h \r 1 (dermal absorption rate = 14 %)	UFA= 10x

UFH= 10x

FQPA SF= 1x	Residential LOC for MOE = 100

	Rabbit Prenatal Developmental Toxicity

LOAEL = 10.0 mg/kg/day based on developmental toxicity findings of
increased resorptions and maternal toxicity based on decreased body
weight gain and decreased food intake/efficiency.

  SEQ CHAPTER \h \r 1 Long-Term Dermal (>6 months)	  SEQ CHAPTER \h \r 1
Oral study NOAEL = 3.4 mg/kg/day

(dermal absorption rate = 14 %)	UFA= 10x

UFH= 10x

FQPA SF= 1x	Residential LOC for MOE = 100

	  SEQ CHAPTER \h \r 1 Rat Oral Carcinogenicity

LOAEL = 9.2 mg/kg/day based on decreased body weight/body weight gain,
kidney tubular casts and atrophy in both sexes; increased incidence of
liver necrosis and erosion/ulceration of the glandular- stomach and
fore-stomach in males.

Inhalation Short- Term (1-30 days)	NOAEL= 0.23 mg/kg/day (air
concentration = 0.001 mg/L)	UFA= 10x

UFH= 10x

FQPA SF= 1x	Residential LOC for MOE = 100	Rat 28-day Inhalation

LOAEL = 6.9 mg/kg/day (air concentration = 0.03 mg/L) based on duodenum
mucosal hyperplasia and respiratory system findings including alveolar
histiocytosis and olfactory atrophy/necrosis in nasal tissue.

Inhalation Intermediate-Term (1-6 months)	NOAEL= 0.23 mg/kg/day (air
concentration = 0.001 mg/L)	UFA= 10x

UFH= 10x

FQPA SF= 1x	Residential LOC for MOE = 100

	Rat 28-day Inhalation

LOAEL = 6.9 mg/kg/day (air concentration = 0.03 mg/L) based on duodenum
mucosal hyperplasia and respiratory system findings including alveolar
histiocytosis and olfactory atrophy/necrosis in nasal tissue.

Inhalation Long-Term (>6 months)	NOAEL= 0.23 mg/kg/day (air
concentration = 0.001 mg/L)	UFA= 10x

UFH= 10x

FQPA SF= 1x	Residential LOC for MOE = 100

	Rat 28-day Inhalation

LOAEL = 6.9 mg/kg/day (air concentration = 0.03 mg/L) based on duodenum
mucosal hyperplasia and respiratory system findings including alveolar
histiocytosis and olfactory atrophy/necrosis in nasal tissue.

Cancer (oral, dermal, inhalation) 	Classification:  “Not likely to be
Carcinogenic to Humans” based on the absence of significant tumor
increases in two adequate rodent carcinogenicity studies.

Point of Departure (POD) = A data point or an estimated point that is
derived from observed dose-response data and  used to mark the beginning
of extrapolation to determine risk associated with lower environmentally
relevant human exposures.  NOAEL = no observed adverse effect level.
LOAEL = lowest observed adverse effect level.  UF = uncertainty factor.
UFA = extrapolation from animal to human (interspecies).  UFH =
potential variation in sensitivity among members of the human population
(intraspecies).  UFL = use of a LOAEL to extrapolate a NOAEL.  UFS = use
of a short-term study for long-term risk assessment.  UFDB = to account
for the absence of key date (i.e., lack of a critical study).  FQPA SF =
FQPA Safety Factor.  PAD = population adjusted dose (a = acute, c =
chronic).  RfD = reference dose.  MOE = margin of exposure.  LOC = level
of concern.  N/A = not applicable.

Table 4.  Summary of Toxicological Doses and Endpoints for
Pyraclostrobin for Use in Occupational Human Health Risk Assessments

Exposure/

Scenario	Point of Departure	Uncertainty Factors	Level of Concern for
Risk Assessment	Study and Toxicological Effects

Dermal Short-Term (1-30 days)	NOAEL= 5.0 mg/kg/day

  SEQ CHAPTER \h \r 1 (dermal absorption rate = 14 %)	UFA=10x

UFH=10x

Occupational LOC for MOE = 100	Rabbit Prenatal Developmental Toxicity

LOAEL = 10.0 mg/kg/day based on developmental toxicity findings of
increased resorptions.

Dermal Intermediate-Term (1-6 months)	Oral study NOAEL = 5.0 mg/kg/day

  SEQ CHAPTER \h \r 1 (dermal absorption rate = 14 %)	UFA= 10x

UFH= 10x

	Occupational LOC for MOE = 100

	Rabbit Prenatal Developmental Toxicity

LOAEL = 10.0 mg/kg/day based on developmental toxicity findings of
increased resorptions.

  SEQ CHAPTER \h \r 1 Long-Term Dermal (>6 months)	  SEQ CHAPTER \h \r 1
Oral study NOAEL = 3.4 mg/kg/day

(dermal absorption rate = 14 %)	UFA= 10x

UFH= 10x

	Occupational LOC for MOE = 100

	  SEQ CHAPTER \h \r 1 Rat Oral Carcinogenicity

LOAEL = 9.2 mg/kg/day based on decreased body weight/body weight gain,
kidney tubular casts and atrophy in both sexes; increased incidence of
liver necrosis and erosion/ulceration of the glandular- stomach and
fore-stomach in males.

Inhalation Short- Term (1-30 days)	NOAEL= 0.23 mg/kg/day (air
concentration = 0.001 mg/L)	UFA= 10x

UFH= 10x

	Occupational LOC for MOE = 100	Rat 28-day Inhalation

LOAEL = 6.9 mg/kg/day (air concentration = 0.03 mg/L) based on duodenum
mucosal hyperplasia and respiratory system findings including alveolar
histiocytosis and olfactory atrophy/necrosis in nasal tissue.

Inhalation Intermediate-Term (1-6 months)	NOAEL= 0.23 mg/kg/day (air
concentration = 0.001 mg/L)	UFA= 10x

UFH= 10x

	Occupational LOC for MOE = 100

	Rat 28-day Inhalation

LOAEL = 6.9 mg/kg/day (air concentration = 0.03 mg/L) based on duodenum
mucosal hyperplasia and respiratory system findings including alveolar
histiocytosis and olfactory atrophy/necrosis in nasal tissue.

Inhalation Long-Term (>6 months)	NOAEL= 0.23 mg/kg/day (air
concentration = 0.001 mg/L)	UFA= 10x

UFH= 10x

	Occupational LOC for MOE = 100

	Rat 28-day Inhalation

LOAEL = 6.9 mg/kg/day (air concentration = 0.03 mg/L) based on duodenum
mucosal hyperplasia and respiratory system findings including alveolar
histiocytosis and olfactory atrophy/necrosis in nasal tissue.

Cancer (oral)	Classification:  “Not likely to be Carcinogenic to
Humans” based on the absence of significant tumor increases in two
adequate rodent carcinogenicity studies.

Point of Departure (POD) = A data point or an estimated point that is
derived from observed dose-response data and  used to mark the beginning
of extrapolation to determine risk associated with lower environmentally
relevant human exposures.  NOAEL = no observed adverse effect level.
LOAEL = lowest observed adverse effect level.  UF = uncertainty factor.
UFA = extrapolation from animal to human (interspecies).  UFH =
potential variation in sensitivity among members of the human population
(intraspecies).  UFL = use of a LOAEL to extrapolate a NOAEL.  UFS = use
of a short-term study for long-term risk assessment.  UFDB = to account
for the absence of key date (i.e., lack of a critical study).  MOE =
margin of exposure.  LOC = level of concern.  N/A = not applicable.

3.5	Endocrine disruption  TC \l2 "3.5	Endocrine disruption

EPA is required under the FFDCA, as amended by FQPA, to develop a
screening program to determine whether certain substances (including all
pesticide active and other ingredients) “may have an effect in humans
that is similar to an effect produced by a naturally occurring estrogen,
or other such endocrine effects as the Administrator may designate.”
Following recommendations of its Endocrine Disruptor Screening and
Testing Advisory Committee (EDSTAC), EPA determined that there was a
scientific basis for including, as part of the program, the androgen and
thyroid hormone systems, in addition to the estrogen hormone system.
EPA also adopted EDSTAC’s recommendation that the Program include
evaluations of potential effects in wildlife.  For pesticide chemicals,
EPA will use FIFRA and, to the extent that effects in wildlife may help
determine whether a substance may have an effect in humans, FFDCA
authority to require the wildlife evaluations.  As the science develops
and resources allow, screening of additional hormone systems may be
added to the Endocrine Disruptor Screening Program (EDSP).

When additional appropriate screening and/or testing protocols being
considered under the Agency’s EDSP have been developed, pyraclostrobin
may be subjected to further screening and/or testing to better
characterize effects related to endocrine disruption.

4.0	Dietary Exposure/Risk Characterization  TC \l1 "4.0	Dietary
Exposure/Risk Characterization

References:

Pyraclostrobin.  PP#’s 5F7002 and 5E7014.  Petition for Tolerances on
Cotton and Belgian Endive, and An Increased Tolerance on the Berries
Crop Group. Submission of Requested Field Trial Data on Mustard Greens
(PP#3F6581).  Submission of Additional Field Trial Data on Fruiting
Vegetables (PP#0F6139), Cucurbit Vegetables (PP#0F6139), Sunflower
(PP#2F6431), Mint (PP#2F6431), and Grape(PP#0F6139).  Summary of
Analytical Chemistry and Residue Data.  (Reg. No. 7969-198). DP Number
327899; J. Stokes; 03/30/07.

Pyraclostrobin. PP5E7014.  Amendment.  Petition for Tolerance on Belgian
Endive.  Additional Discussion of Residue Data and Its Use For
Adjustment of Previous Tolerance Recommendation.  Request for Revised
Sections B and F. DP Number 339733; J. Stokes; 05/30/07.

4.1	Pesticide Metabolism and Environmental Degradation  TC \l2 "4.1
Pesticide Metabolism and Environmental Degradation

4.1.1	Metabolism in Primary Crops  TC \l3 "4.1.1	Metabolism in Primary
Crops

Adequate metabolism studies with pyraclostrobin on grapes, potatoes, and
wheat have previously been reviewed (D269668, L. Cheng, 11/28/01) in
conjunction with PP#0F06139.  The results of these studies indicate that
the metabolism of pyraclostrobin is similar in the three crops
investigated.  The HED Metabolism Assessment Review Committee (MARC)
concluded that the nature of the residue in plants is understood (HED
Metabolism Committee Decision Memo; D278044, L. Cheng, 10/9/01).  For
purposes of tolerance setting and risk assessment, the terminal residues
of concern in plants consist of pyraclostrobin and its desmethoxy
metabolite (BF 500-3).

4.1.2	Metabolism in Livestock  TC \l3 "4.1.2	Metabolism in Livestock

Adequate metabolism studies with pyraclostrobin on ruminants and laying
hens were previously reviewed (D269668, L. Cheng, 11/28/01) in
conjunction with PP#0F06139.  The HED MARC has determined that for
purposes of tolerance setting and risk assessment, the residues of
concern in livestock commodities consist of pyraclostrobin and its
metabolites convertible to 1-(4-chlorophenyl)-1H-pyrazol-3-ol and
1-(4-chloro-2-hydroxyphenyl)-1H-pyrazol-3-ol (HED Metabolism Committee
Decision Memo; D278044, L. Cheng, 10/9/01).

4.1.3	Analytical Methodology  TC \l3 "4.1.3	Analytical Methodology

Enforcement Method for Plants

Two adequate methods were proposed for enforcing tolerance for residues
of pyraclostrobin and BF 500-3 in/on plant commodities: a LC/MS/MS
method (BASF Method D9808), and an HPLC/UV method (BASF Method D9904).
The validated method LOQ for both pyraclostrobin and BF 500-3 is 0.02
ppm in all tested plant matrices, for a combined LOQ of 0.04 ppm.
Adequate independent method validation and radiovalidation data were
submitted for both methods (D269668, 11/28/01, L. Cheng), and both
methods were forwarded to ACB/BEAD for a petition method validation
(D269850, 11/8/00, L. Cheng).

Samples from the current crop field trials and cotton processing study
were analyzed for residues of pyraclostrobin and BF 500-3 using the
LC/MS/MS method (BASF Method D9908, MRID 46710001 (currently under BEAD
review)).  For all commodities, except cottonseed oil, residues were
extracted with methanol:water:2N HCl (70:25:5) and filtered.  For oil
samples, residues were extracted with hexane, partitioned into
acetonitrile, concentrated, and redissolved in methanol:water:2N HCl
(70:25:5).  Residues from all samples were then cleaned up by
partitioning into cyclohexane.  Residues of pyraclostrobin and BF 500-3
were determined by LC/MS/MS, using external standards.  For each
analyte, the validated method LOQ is 0.02 ppm and the LOD is 0.004-0.005
ppm.

Based on the concurrent method validation data, Method D9908 is adequate
collecting data on residues of pyraclostrobin and BF 500-3 in berries,
cotton commodities, cucurbit vegetables, fruiting vegetables, grape,
mint, mustard greens, and sunflower seed.

Analytical Methods - Livestock

Two methods have also been proposed for enforcing tolerances for
livestock commodities:  HPLC/UV method 439/0 and Method 446 (consisting
of GC/MS method 446/0 and LC/MS/MS method 446/1).  The HPLC/UV method
determines residues of pyraclostrobin per se.  Method 446 has a
hydrolysis step, and determines residues of pyraclostrobin and its
metabolites as BF 500-5 and BF 500-8.  The validated method LOQs for BF
500-5 type residues, in parent equivalents, are 0.01 ppm for milk and
0.05 ppm for tissues, and the validated LOQs for BF 500-8 type residues,
in parent equivalents, are 0.01 ppm for milk and 0.05 ppm for tissues.
Independent method validation data for the HPLC/UV and LC/MS/MS methods
are acceptable (D269668, 11/28/01, L. Cheng).  Radiovalidation data
submitted for the GC/MS and LC/MS/MS methods are adequate for liver and
milk, and marginal for muscle.  Method 446 has been forwarded to
ACB/BEAD for petition method validation.  As poultry tolerances are not
currently necessary, an enforcement method for poultry commodities is
not required at the present time.

Multiresidue Methodology (860.1360)

Data pertaining to the multiresidue methods testing of pyraclostrobin
and its desmethoxy metabolite were reviewed (PP#0F6139, D269668,
11/28/01, L. Cheng).  Pyraclostrobin was successfully evaluated through
several of the FDA protocols, while recovery of BF 500-3 was
unsuccessful in all protocols.  Pyraclostrobin was completely recovered
through Protocol D (in grape) and E (in grape), and partially recovered
through Protocol F (in peanut).  Metabolite BF 500-3 had poor peak shape
and inadequate sensitivity with Protocol C columns, and therefore, was
not further analyzed under Protocol D, E, and F.  The results of the
multiresidue testing for pyraclostrobin were forwarded to FDA on 1/4/02
for the purpose of updating PAM, Volume I.

4.1.4	Storage Stability Data  TC \l3 "4.1.4	Storage Stability Data

e at ≤-10ºC in fortified samples of grape juice (juices), sugar beet
tops (leafy vegetables), sugar beet roots (root crop), tomato
(fruit/fruiting vegetable), and wheat grain (non-oily grain) and wheat
straw (dry feed) for up to 25 months, and in fortified samples of peanut
nutmeats (oilseed) and peanut oil for up to 19 months (D269668,
L. Cheng, 11/28/01).

Conclusions.  Adequate storage stability data are available to support
the samples storage conditions and intervals from the current field
trials for cotton and Belgian endive, and for the cottonseed processing
study.  The storage stability data on tomato support the berry, fruit
vegetable, grape, and cucurbit vegetable field trials, and the storage
stability data on sugar beet tops support the mustard greens and mint
field trials.  The storage stability data on peanut nutmeats and oil
support the residue data on sunflower seeds and cotton seed and oil, and
the storage stability data on wheat straw support the data on cottonseed
hulls and gin byproducts.

4.1.5	Magnitude of the Residue in Plants  TC \l3 "4.1.5	Magnitude of the
Residue in Plants

46512002.der (Cucurbit vegetables)	46512003.der (Sunflower)	46637701.der
(Berries) 46665501.der (Fruiting vegetables)	46665502.der (Mint)
46665504.der Grape)

46665506.der (Mustard greens)	46685901.der (Cotton)

BASF submitted cotton field trials supporting a new use for
pyraclostrobin (EC) on cotton, along with previously requested
additional field trials on mustard greens supporting the existing use on
Brassica leafy greens.  In addition, BASF submitted supplemental field
trials from the U.S. and Canada on berries, cucurbit vegetables,
fruiting vegetables, grape, mint and sunflower.  These field trials were
conducted to support uses on these crops in Canada, and therefore are
not discussed in detail in this document.    SEQ CHAPTER \h \r 1 The
results from these studies are summarized in Table 5 and discussed
below, along with the previously reviewed data on the above crops.
Additionally, the data on berries were submitted to support an increase
in the berries crop group tolerance.

Table 5.	Summary of Residue Data from Crop Field Trials with
Pyraclostrobin.

Crop/commodity	Total Applic. Rate  (lb ai/A)	PHI (days)	Combined
Pyraclostrobin Residues (ppm) 1

	n	Min.	Max.	HAFT 2	Median	Mean	Std. Dev.

Berries (0.72 lb ai/A total application rate, 0-day PHI)

Red raspberries	0.73-0.75	0	6	0.76	1.33	1.28	1.01	1.04	0.22

Blueberries	0.73-0.75	0	12	1.11	2.52	2.33	1.55	1.73	0.50

Overall Berries	0.73-0.75	0	18	0.76	2.52	2.33	1.32	1.50	0.54

Cotton (0.80 lb ai/A total application rate, 30-day PHI)

Undelinted, seed	0.80-0.85	29-33	24	<0.04	0.17	0.15	0.03	0.05	0.04

Gin byproducts 3	picker	0.80-0.85	29-30	6	2.04	25.06	20.35	3.38	8.60
9.60

	stripper

30-32	6	1.05	2.00	1.91	1.74	1.59	0.42

Cucurbit Vegetables (1.2 lb ai/A total application rate, 0-day PHI)

Cucumber	1.17-1.20	0	8	0.053	0.186	0.180	0.102	0.106	0.057

Cantaloupe	1.18-1.20	0	4	0.099	0.379	0.338	0.202	0.218	0.143

Squash	1.16-1.20	0	8	0.094	0.213	0.190	0.126	0.131	0.037

Cucurbits	1.16-1.20	0	20	0.053	0.379	0.338	0.118	0.139	0.082

Fruiting Vegetables (1.2 lb ai/A total application rate, 0-day PHI)

Tomato	0.54-0.58	0	14	0.096	0.366	0.304	0.178	0.192	0.086

Pepper	0.55-0.61	0	6	0.092	0.701	0.689	0.344	0.375	0.268

Fruiting Vegetables	0.54-0.61	0	20	0.092	0.701	0.689	0.207	0.247	0.177

Grape (0.55 lb ai/A total application rate, 14-day PHI)

Grape	0.56-0.57	13-14	8	0.56	1.93	1.86	1.28	1.30	0.48

Mustard Greens (0.80 lb ai/A total application rate, 3-day PHI)

Mustard greens	0.8	0	10	5.5	14.4	12.6	8.3	8.9	2.5

3	6	1.4	5.5	5.1	3.7	3.4	1.7

7	6	1.0	2.3	2.2	1.9	1.7	0.6

14-15	6	0.18	1.2	1.0	0.31	0.5	0.4

Sunflower (0.40 lb ai/A total application rate, 21-day PHI)

Seed	0.40	21	2	<0.04	<0.04	<0.04	0.02	0.02	NA

Mint (0.80 lb ai/A total application rate, 14-day PHI)

Mint tops	0.91-0.92	7	4	2.25	3.65	3.55	2.96	2.96	0.69

1	Residues of pyraclostrobin and BF 500-3 are expressed in parent
equivalents, and the LOQ is 0.02 ppm for each analyte or 0.04 ppm for
the combined residues.  For purposes of calculating median and mean and
standard deviation, ½ LOQ (0.01 ppm) was used for residue values of
each analyte that were <LOQ.

2	HAFT = Highest Average Field Trial.

3	Samples of gin byproducts were obtained from trials harvested using
mechanical picker (3 tests) and strippers (3 tests).

4	A sixth application was inadvertently applied to cherries.

Brassica Leafy Green, Subgroup 5B

Mustard Greens.  The Agency previously reviewed residue data from five
mustard green field trials conducted in Zones 2, 4, 5, 6 and 10 during
2001 (PP#3F6581, D281042, L. Cheng, 7/26/04).  In each trial,
pyraclostrobin (20% WDG) was applied to mustard greens as four broadcast
foliar applications at 0.2 lb ai/A, at RTIs of with a 6 to 8 days, for a
total of 0.8 lb ai/A/season (1x rate).  Applications were made using
ground equipment at 12-31 gal/A, and included the use of a spray
adjuvant.  Samples of mustard greens were harvested 0, 3, 7, 10, and 14
DAT; the label specified PHI is 3 days.  Samples were analyzed using an
adequate LC/MS/MS method (BASF Method Number D9908), and the sample
storage conditions and intervals (6.6 months) were supported by the
available storage stability data.

In these five field trials, the combined pyraclostrobin residues were
1.13-13.40 ppm in/on 10 samples of mustard greens harvested at the
labeled 3-day PHI.  The HAFT residues were 12.95 ppm and average
residues were 7.13 ppm.  Based on these data, the Agency established a
16 ppm tolerance for pyraclostrobin residues in/on Brassica leafy
greens.  However, as a condition of registration the Agency also
requested data from three additional field trials in Zones 2, 3, and 10.

In response to this request, BASF submitted field trial data from six
mustard green field trials conducted in Zones 2, 3 and 10 during 2004
and 2005.  In each test, pyraclostrobin (20% or 12.8% WDG) was applied
to mustard greens as four broadcast foliar applications at 0.2 lb ai/A
during vegetative crop development, for a total rate of 0.8 lb ai/A (1x
rate).  Applications were made RTIs of 6-8 days using ground equipment
at 13-32 gal/A, and each application included the use of a non-ionic
surfactant at 0.25% of the spray volume.  For the 2004 tests, single
control and duplicate treated samples of mustard greens were harvested
at 0 days after the last application (0 DAT).  For the 2005 tests,
single control and duplicate treated samples of mustard greens were
harvested at 0, 3, 7, and 14-15 DAT, with the exception of the CA test
in which 0-DAT samples were not collected.   Samples were stored frozen
for up to 8.7 months prior to analysis, an interval supported by
available storage stability data.  Samples were analyzed for residues of
pyraclostrobin and BF 500-3 using an adequate LC/MS/MS method (BASF
Method D9908), which has a LOQ of 0.02 ppm for each analyte.

In these tests, combined pyraclostrobin residues in/on mustard greens
were 5.5-14.4 ppm at 0 DAT and declined steadily to 0.18-1.20 ppm at
14-15 DAT.  At the label-specified preharvest interval of 3 days,
combined residues were 1.4-5.5 ppm.  Average combined residues were 8.9
ppm at 0 DAT, 3.4 ppm at 3 DAT, 1.7 ppm at 7 DAT, and 0.5 ppm at ~14
DAT.  These data satisfy the outstanding condition of registration data
requirement for additional field trial data.

Belgian Endive

The submitted field trial data ( MRID 46713801) do not support the
proposed use of pyraclostrobin on Belgian endive.  The field trial data
are inadequate, because the application method used does not agree with
the proposed use pattern.  The label proposes application by an overhead
sprayer, while the roots transverse on a conveyor belt or while in place
in forcing trays.  Unfortunately, most of the submitted residue data
were generated using a hand wand and back pack sprayer (5 of 6
applications).  Only a few data points were generated using an overhead
sprayer.  The field trials were conducted in California.  The trials
represent NAFTA growing region 10.  The number of trials and geographic
representation are adequate for Belgian endive.  Two root spray
applications of BAS 510 (boscalid) and BAS 500 F (pyraclostrobin) were
made at two application rates prior to cold storage and prior to
forcing.  One set of Belgian endive was treated at rates (0.5X) of
approximately 0.011 lb pyraclostrobin per 875 lb roots (plus boscalid).
Another set was also treated at 1X rates of approximately 0.022 lb
pyraclostrobin per 875 lb roots (plus boscalid.

The maximum storage interval for treated samples in this study was 198
days (see Table 4).  The storage stability for pyraclostrobin in/on
Belgian endive was not determined in this study.  However, in a
previously submitted storage stability study pyraclostrobin residues
were shown to be stable for 18 months.  Pyraclostrobin residues in/on
Belgian endive treated at the 0.5X rate ranged from 0.05 to 2.90 ppm
(1.55 ± 1.24).  Also, pyraclostrobin residues ranged from 1.48 to 7.96
ppm in samples treated at the 1X rate.

If IR4 still wants a Section 3 registration, then the following are
needed:

Use directions in Section B must match the application method used in
Section D for residue data collection;

The tolerance proposal in Section F must be supported by the application
method used in Section D for residue data collection;

Additional residue data that adequately reflect the use direction in
Section B must be submitted. (HED recommends that the petitioner submit
a protocol for HED review and comment before any residue data collection
begins.); and

The label should include a requirement for chemical-resistant gloves.

HED recommends that the label rate be revised to clearly define the
amounts to be used per application and the total per season.  In
addition, the petitioner should define how the spray is applied to the
roots in the forcing trays (.i.e., trays are stationary or are moving on
a conveyor belt).  A revised Section B must be submitted to adequately
reflect the petitioner’s intentions as to application rates and
directions.  Refer to section 9.1 for details.

Cotton

In twelve field trials conducted in Zones 2, 4, 6, 8 and 10 during 2004,
pyraclostrobin (20% WDG) was applied to cotton four times; first as an
in-furrow application at planting at 0.20-0.21 lb ai/A, followed by
three broadcast foliar applications during boll development at 0.20-0.24
lb ai/A at RTIs of 5-9 days, for a total of 0.80-0.85 lb ai/A/season (1x
proposed rate).  All applications were made using ground equipment at
5-10 gal/A for the in-furrow application and at 11-39 gal/A for the
foliar applications.  Foliar applications included the use of a
non-silicone surfactant at 0.25% of the spray volume.  Single control
and duplicate treated cotton samples were harvested by hand (1 site), or
by mechanical picker (7 sites) or stripper (4 sites) at 29-33 DAT.
Samples of undelinted seeds were collected from all sites, and cotton
gin byproducts (gin trash) were collected from six sites (3 stripper and
3 picker).  All samples were stored at <-10 ºC for up to 6.6 months
prior to analysis, an interval which is supported by the available
storage stability data.

Samples of cottonseed and gin byproducts were analyzed for residue of
pyraclostrobin and BF 500-3 using a LC/MS/MS method (BASF Method D9908),
which was adequately validated in conjunction with the field trial
analyses.  The method LOQ and LOD for each analyte is 0.02 and 0.005
ppm, respectively.

At maturity (29-33 DAT), residues in/on 24 treated samples of undelinted
cotton seed were <0.02-0.14 ppm for pyraclostrobin and <0.02-0.028 ppm
for BF 500-3, for combined residues of <0.04-0.17 ppm.  Average combined
residues were 0.05 ppm in/on undelinted seeds, and HAFT residues were
0.15 ppm.  Residues in/on gin trash were generally higher for cotton
harvested using a picker than for cotton harvested using a stripper.
Following harvest with a picker, combined residues in/on six samples of
gin trash were 2.04-25.06 ppm and averaged 8.60 ppm.  Following harvest
with a stripper, combined residues in/on six samples of gin trash were
1.05-2.00 ppm and averaged 1.59 ppm.

Berries, Group 13

Blueberries and Raspberries.  Adequate field trial data are available
supporting the use of pyraclostrobin (WDG) on the berries crop group in
the U.S. (PP#0F6139, D269668, 11/28/01, L. Cheng).  In a total of nine
field trials conduct in the U.S. during 1999, pyraclostrobin (20% WDG)
was applied to red raspberries (3 tests) and blueberries (6 tests) as
four broad foliar applications during fruit development at 0.18-0.19 lb
ai/A at RTIs of 6-7 days, for a total of 0.72-0.74 lb ai/A (1x rate).
Applications were made using ground equipment in 50-102 gal/A, and
included the use of a non-silicone spray adjuvant.  Single control and
duplicate treated samples of blueberries and raspberries were harvested
from each test immediately following the last application (0 DAT).
Samples were stored frozen for up to 3 months and then analyzed for
residues of parent and BF 500-3 using BASF Method D9808.  C  SEQ CHAPTER
\h \r 1 ombined pyraclostrobin residues were <0.12-0.69 ppm in/on
highbush blueberries and <0.46-0.97 ppm in/on red raspberries.  Based on
these residues, the Agency established a 1.3 ppm tolerance on the
berries crop group.

To support the use of pyraclostrobin on berries grown in Canada, BASF
recently submitted additional data from three raspberry field trials
conducted in Zones 5, 5B, and 12, and six blueberry field trials were
conducted in Zones 1A and 5 during 2004.  At each test location,
pyraclostrobin (12.8% WDG) was applied as four broadcast foliar
applications at 0.17-0.19 lb ai/A during fruit development at RTIs of
6-8 days, for totals of 0.73-0.75 lb ai/A (1x rate, 0.82-0.84 kg ai/ha).
 Applications were made using ground equipment at 29-85 gal/A (267-798
L/ha), and included the use of a non-ionic surfactant at 0.25% of the
spray volume.  Single control and duplicate treated samples of mature
berries were harvested from each test at 0 DAT.  Samples were stored
frozen for up to 6 months prior to analysis, and analyzed using BASF
Method D9908, which was adequately validated in conjunction with the
field trial analyses.  The method LOQ and LOD is 0.02 and 0.004 ppm for
each analyte in berries.

In the 2004 field trials, combined pyraclostrobin residues were
0.76-1.33 ppm in/on six samples of red raspberries and 1.11-2.52 ppm
in/on 12 samples of blueberries.  Combined residues averaged 1.04 and
1.73 ppm for raspberries and blueberries, respectively, and HAFT
residues were 1.28 and 2.33 ppm.  For all nine berry tests, combined
residues averaged 1.50 ppm.  As residue in these field trials exceeded
the current U.S. tolerance for the berries crop group, BASF has proposed
increasing the tolerance for berries to 4.0 ppm.

Conclusions:  The required field trials on cotton and the supplemental
field trials on, mustard greens and berries are adequate and support the
proposed or existing uses of pyraclostrobin on these crops.  Together
with the previously submitted field trials, the number and geographic
distribution of the field trials on these crops are adequate, and the
appropriate samples were collected at the proposed PHIs.

Although the cotton field trials were conducted using the 20% WDG
formulation and the proposed use on cotton is for the 2 lb/gal EC
formulation, the cotton field trial data for the WDG will support the
use of the EC formulation, as previously submitted side-by-side field
trials using tomato, cucumber and grape have shown that residues
resulting from the two types of formulations are similar.

Several deficiencies were found in the Belgian endive field residue
trials.  Most importantly, the application method used in the field
residue trials does not agree with the proposed use pattern.

The submitted supplemental field trials on fruiting vegetables (tomato
and peppers) were also adequate, but are not useful for assessing the
current U.S. tolerance as the field trials were conducted at 0.5x the
maximum seasonal use rate on existing U.S. labels.  However, sufficient
tomato and pepper field trials are already available to support the
existing use on fruiting vegetables.

4.1.6	Magnitude of the Residue in Processed Food/Feed  TC \l3 "4.1.6
Magnitude of the Residue in Processed Food/Feed

46685902.der (cotton)

For the new cotton processing study, pyraclostrobin (20% WDG) was
applied to cotton in a single trial as a combination of an in-furrow
application at 1.0 lb ai/A followed by three broadcast foliar
applications during boll development at 1.0 lb ai/A/application, for a
total of 4.0 lb ai/A/season (5x maximum proposed rate).  Following
applications at a 5x rate, combined pyraclostrobin residues in/on
undelinted cottonseed at 30 DAT were 0.106 and 0.176 ppm and averaged
0.14 ppm.  Combined residues were <0.04 ppm in/on all cotton processed
commodities, for processing factors of <0.3x for each commodity.  The
maximum theoretical processing factor for undelinted cottonseed is 6.3x
(oil).

Conclusions.  The new cotton processing study is adequate and indicates
that residues do not concentrate in cottonseed hulls, meal or oil.

4.1.7	Magnitude of the Residue in Meat, Milk, Poultry, and Eggs  TC \l3
"4.1.7	Magnitude of the Residue in Meat, Milk, Poultry, and Eggs

Adequate feeding studies were reviewed in conjunction with an earlier
pyraclostrobin petition (D269668, 11/28/01, L. Cheng).  In the ruminant
feeding study, dairy cows were dosed orally for 28 days with
pyraclostrobin at levels equivalent to 8.8, 27.2, and 89.6 ppm in their
diet, and in the poultry feeding study, laying hens were dosed orally
for 30 days with pyraclostrobin at levels equivalent to 0.28, 0.88, and
3.01 ppm in their diet.

The current tolerances for livestock commodities were established based
on results from the available feeding studies and the Agency’s
estimated dietary burdens for pyraclostrobin residues, which were
previously calculated to be 36.3 ppm for beef cattle, 35.4 ppm for dairy
cattle, and 0.35 ppm for poultry (D269668, 11/28/01, L. Cheng).

The new livestock feedstuffs included in the current petition are
cottonseed, hulls, meal, and gin byproducts.  The potential dietary
exposure of livestock to pyraclostrobin residues has been recalculated
below in Table 6 using recent Agency guidance on calculating dietary
exposure from “reasonably balanced” livestock diets to include all
feedstuffs with existing tolerances and those proposed.  Based on these
recalculated dietary exposure levels and the residue data from the
ruminant feeding study, the existing tolerances are adequate for milk,
meat, fat, meat byproducts (except liver), and liver of cattle, goats,
horses, and sheep.  In fact, the current tolerances of 1.5 ppm for liver
of cattle, goats, horses, and sheep could be reasonably lowered to 1.0
ppm.

In addition, the existing tolerances for hog commodities can be deleted
as quantifiable residues are unlikely to occur in hog [40 CFR
§180.6(a)(2)] as residues of pyraclostrobin and its metabolites were
<LOQ in meat, fat, kidney and liver of cattle dosed at 8.8 ppm, which is
46x the calculated dietary burden for swine.  As noted in earlier
pyraclostrobin petitions (D269668, 11/28/01, L. Cheng), the data from
the poultry feeding and metabolism studies indicates that tolerances for
residues in poultry commodities are not required at the present time.

Table 6. Livestock dietary burdens for pyraclostrobina.

	% Diet b	Residue (ppm)

Feedstuff	Type	Tolerance,

ppm	% Dry Matter	Beef	Dairy	Poultry	Swine	Beef 	Dairy 	Poultry 	Swine

barley hay	R	25	88	10	25	-	-	2.8	7.1	-	-

cotton gin byproducts	R	30.	90	5	-	-	-	1.7	-	-	-

legume, hay (cowpea)	R	25	86	-	15	-	-	-	4.4	-	-

barley, grain	CC	0.4	88	50	45	20	20	0.23	0.20	0.08	0.08

corn, field, grain	CC	0.1	88	20	-	60	65	0.023	-	0.06	0.065

cotton, undelinted seed	PC	0.3	85

15

0.053

sunflower (meal)	PC	0.3	92	15

20	15	0.049

0.06	0.045

Totals

100	100	100	100	4.8	11.8	0.20	0.19

a All data are based on Table 1 Feedstuffs (October 2006), a revision of
feedstuffs data found in Table 1 (180.1000 OPPTS Test Guidelines).
Residue levels for beef and dairy are corrected for moisture content and
are determined by formula: tolerance / %DM x % in diet.  Residue levels
for poultry and swine are considered “as-is” and are determined by
formula: tolerance  x   % in diet.  R: roughage; CC: carbohydrate
concentrate;  PC:  protein concentrate.

b Typical compositions of daily rations for the animals of choice for
Table 1 data  follow:

Feedlot beef have a daily ration of 15-40 %  R, 45-80 %  CC, and 5-15 %
PC.  As the slaughter time (last 3 months) gets closer, then the beef
cattle are fed higher amounts of CC (up to 80 %), and lower amounts of
R (15-20 %) and PC (5-10 %).  The average life span for feedlot beef is
16-18 months   Most of feedlot beef are slaughtered in 4 major centers
located in the Midwest and the processed meat is “boxed” and shipped
to distributors for sale to local grocers.  Commercial ground beef
(75-93 % lean) is produced from the combination of feedlot beef (60-70 %
lean) and other lean meat sources, i.e., beef cows and bulls from
cow-calf operations, imported lean meat trimmings, and non-lactating
dairy cows.

High volume milk-producing lactating dairy cows have a daily ration of
45 % R, 40-45 % CC, and 10-15 % PC.  Dairy cows usually produce 2-3
calves before slaughter. The average life span of the lactating dairy
cow is 3-4 years.  Upon slaughter, much of the meat is used in ground
beef and processed foods e.g., deli meats, soups, frozen
dinners/entrees.

A laying hen that will give a steady egg production is fed 75-80 % CC
and 20-25 % PC.   The life span can be up to 18 months.  In general,
laying hens are not processed and marketed as whole or cut-up chickens.
Much of the layer meat is used in processed food products, e.g., deli
meats, soups, canned chicken, etc.  (Note:  The laying hen is the animal
of choice.  Frying and rotisserie chickens come from the broiler, a fast
food chicken, weighing 3.5-4.0 lb.), and an animal that is raised in a
very short time.  The average life span is 38-42 days.  The broiler diet
contains 85-90 % CC and 10-15 % PC.

A marketable hog diet that will give steady growth would have 80-85 % CC
and 15-20 % PC.  Most of the US hog production is confined to “mega”
operations.  Animals are born in in-house nurseries, and simply moved to
connecting buildings as the animal grows until slaughter (250 lb
finished animal in 6 months). These animals provide meat for the
“fresh pork” market.

Note:  These guidelines are not to be used for pesticide residues that
bioaccumulate.  Contact Health Effects Division, OPP, EPA for these
types of pesticides.

4.1.8	Confined and Field Rotational Accumulation in Rotational Crops  TC
\l3 "4.1.8	Confined and Field Accumulation in Rotational Crops

An adequate confined rotational crop study is available on
pyraclostrobin (PP#0F6139, D269668, L. Cheng, 11/28/01; D314519, L.
Cheng, 05/05/05).  The confined study indicates that the metabolism of
pyraclostrobin in rotated crops is similar but more extensive than that
in primary crops.  Pyraclostrobin undergoes demethoxylation to yield BF
500-3, followed by further degradation to medium polar and polar
metabolites, and subsequent conjugation reactions and incorporation into
natural products.  The MARC (D278044, L. Cheng, 10/09/01) concluded that
the residues of concern in rotational crops consist of pyraclostrobin
and metabolite BF 500-3.

An adequate limited field rotational crop study is available (PP#0F6139,
D269668, L. Cheng, 11/28/01) reflecting six broadcast foliar
applications of pyraclostrobin (EC) to cucumber at 0.19-0.20 lb
ai/A/application and RTIs of 6-8 days, for a total of 1.2 lb
ai/A/season.  This rate is 1x the maximum use rate of any rotated crop.
Average residues of pyraclostrobin and BF 500-3 were each <LOQ in/on RAC
samples from all representative rotational crops (radish, cabbage and
wheat) planted 14 days following the final application to the primary
crop.  These data indicate that the label specified 14-day plant-back
restriction is acceptable for all crops that are not registered for
direction application.

4.1.9	Drinking Water Residue Profile TC \l3 "4.1.9	Drinking Water
Residue Profile

Reference: Drinking Water Assessment for the Use of Pyraclostrobin (P.C.
Code: 099100) on Undelinted Cotton Seed, Cotton Gin By-Products, and
Berries Group 13 (DP Barcode D326246) A. Al-Mudallal, 2/21/07.

The Environmental Fate and Effects Division (EFED) reviewed the proposed
use rates associated with the Section 3 request for the use of
pyraclostrobin on cotton and berries group 13.  EFED concluded that the
proposed use rates are much lower than the use rate on turf, the crop
that was previously selected for the drinking water assessment.
Additionally,  the use rates for the proposed uses on Belgian endive are
considerably lower than the use rate on turf.  Therefore, the estimated
concentrations of pyraclostrobin in drinking water associated with the
last Section 3 request remain valid.

A summation of the previous drinking water assessment is as follows:  A
Tier 2 drinking water assessment was performed using PRZM 3.12/ EXAMS
2.7.97 modeling with index reservoir (IR) scenarios and percent cropped
area (PCA) adjustment factors.  The assessment was based on the highest
registered use rate of pyraclostrobin on turf.  A Florida turf scenario
was used with six ground applications of 0.5 lbs ai/acre, at 14 day