Document ID: EPA-HQ-OPP-2007-0906-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-03-24T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

     OFFICE OF	

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date: 02/21/2008

MEMORANDUM

SUBJECT:	Pyraclostrobin: Human Health Risk Assessment for Proposed Uses
on Oats, Oilseed Group (Canola & Flax), Plus Seed Treatment on Oats,
Canola, and Flax; Tropical Fruits (Avocado, Black Sapote, Canistel,
Mamey Sapote, Mango; Papaya, Sapodilla, & Star Apple); Increased
Tolerance on Barley; Adding Aerial Application to Turf & Ornamentals;
and Adding In-Furrow Applications to Corn, Soybean, and Sugar Beets. PC
Code: 099100, Petition Nos.: 6F7105, 6E7165 and 7E7245.  DP Barcodes
334535, 336189, 342971, 342585, 340585.

		Regulatory Action: Registration Action New Section 3 Uses

		Risk Assessment Type: Single Chemical Aggregate

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

		Kelly O’Rourke, Biologist

		Registration Action Branch 3

		Health Effects Division (7509P)

			AND

		Jerry Stokes, Chemist

		Re-Registration Branch 4

		Health Effects Division (7509P) 

			AND

		Shelia Piper, Chemist

		Alternative Risk Integration Assessment (ARIA) Team

		Risk Integration Minor Use & Emergency Response Branch (RIMUERB)

		Registration Division (7505)

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)



The Registration Division (RD) of the Office of Pesticide Programs (OPP)
has requested that HED evaluate toxicology and residue chemistry data
and conduct dietary, aggregate, and occupational exposure and risk
assessments, as needed, to estimate the risk to human health that will
result from existing and proposed uses of pyraclostrobin.

BASF Corporation submitted a petition (6F7105) requesting the
establishment of pyraclostrobin tolerances and the addition of new
foliar uses on oats, canola, and flax.  In addition, the petitioner
proposed seed treatment on oats, canola, and flax.

BASF Corporation also submitted a label amendment to add aerial
application to a variety of turf and ornamentals onto the Insignia label
(EPA Reg. No. 7969-184).

BASF Corporation also submitted a supplemental label to add an in-furrow
spray application at planting for corn, soybean and sugar beet onto the
Headline® label (EPA Reg. No. 7969-186).

IR-4 submitted a petition (6E7165) requesting the establishment of
pyraclostrobin tolerances and new uses on avocado, black sapote,
canistel, mamey sapote, mango, papaya, sapodilla, star apple, and fresh
herbs on the Pristine® Fungicide label (EPA Reg. No. 7969-199).

IR-4 submitted another petition (7E7245) requesting to increase the
tolerance levels for barley commodities, and to revise the barley
pre-harvest interval (PHI) on the Headline® label (EPA Reg. No.
7969-186).

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.

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 Sheila Piper (ARIA/RIMUERB), and the
occupational/residential exposure assessment by Kelly O’Rourke (RAB3).

Table of Contents

  TOC \f  1.0	Executive Summary	  PAGEREF _Toc191365813 \h  4 

2.0	Ingredient Profile	  PAGEREF _Toc191365814 \h  12 

2.1	Summary of Registered/Proposed Uses	  PAGEREF _Toc191365815 \h  12 

2.2	Physical and Chemical Properties	  PAGEREF _Toc191365816 \h  14 

3.0	Hazard Characterization/Assessment	  PAGEREF _Toc191365817 \h  15 

3.1	Hazard and Dose-Response Characterization	  PAGEREF _Toc191365818 \h
 15 

3.1.1	Database Summary	  PAGEREF _Toc191365819 \h  15 

3.1.2	Toxicological Effects	  PAGEREF _Toc191365820 \h  16 

3.1.3	Dose-response	  PAGEREF _Toc191365821 \h  19 

3.2	Safety Factor for Infants and Children	  PAGEREF _Toc191365822 \h 
20 

3.3	Summary of Toxicological Doses and Endpoints for Use in Human Health
Risk Assessments	  PAGEREF _Toc191365823 \h  21 

3.4	Recommendation for Aggregate Exposure Risk Assessments	  PAGEREF
_Toc191365824 \h  24 

3.5	Endocrine disruption	  PAGEREF _Toc191365825 \h  24 

4.0	Public Health and Epidemiology Data	  PAGEREF _Toc191365826 \h  25 

5.0	Dietary Exposure/Risk Characterization	  PAGEREF _Toc191365827 \h 
25 

5.1  Pesticide Metabolism and Environmental Degradation	  PAGEREF
_Toc191365828 \h  25 

5.1.1	Metabolism in Primary Crops	  PAGEREF _Toc191365829 \h  25 

5.1.2	Metabolism in Livestock	  PAGEREF _Toc191365830 \h  26 

5.1.3	Analytical Methodology	  PAGEREF _Toc191365831 \h  26 

5.1.4	Storage Stability Data	  PAGEREF _Toc191365832 \h  27 

5.1.5	Magnitude of the Residue in Plants	  PAGEREF _Toc191365833 \h  27 

5.1.6	Magnitude of the Residue in Processed Food/Feed	  PAGEREF
_Toc191365834 \h  34 

5.1.7	Magnitude of the Residue in Meat, Milk, Poultry, and Eggs	 
PAGEREF _Toc191365835 \h  35 

5.1.8	Confined and Field Accumulation in Rotational Crops	  PAGEREF
_Toc191365836 \h  38 

5.1.9	Drinking Water Residue Profile	  PAGEREF _Toc191365837 \h  39 

5.1.10	Proposed Tolerances	  PAGEREF _Toc191365838 \h  40 

5.2  Dietary Exposure and Risk	  PAGEREF _Toc191365839 \h  43 

5.3 Anticipated Residue and Percent Crop Treated (%CT) Information	 
PAGEREF _Toc191365840 \h  47 

6.0	Residential (Non-Occupational) Exposure/Risk Characterization	 
PAGEREF _Toc191365841 \h  47 

7.0	Aggregate Risk Assessments and Risk Characterization	  PAGEREF
_Toc191365842 \h  48 

8.0	Cumulative Risk Characterization/Assessment	  PAGEREF _Toc191365843
\h  49 

9.0	Occupational Exposure/Risk Pathway	  PAGEREF _Toc191365844 \h  49 

9.1	Short-/Intermediate-Term Handler Risk	  PAGEREF _Toc191365845 \h  49

9.2	Short-/Intermediate-Term Postapplication Risk	  PAGEREF
_Toc191365846 \h  55 

10.0	Data Needs and Label Recommendations	  PAGEREF _Toc191365847 \h  58

10.1	Residue Chemistry Data Needs and Label Recommendations	  PAGEREF
_Toc191365848 \h  58 

10.2	Occupational Label Recommendations	  PAGEREF _Toc191365849 \h  60 

11.0	International Residue Limit Status	  PAGEREF _Toc191365850 \h  60 

12.0	Appendix: Toxicity Profile	  PAGEREF _Toc191365851 \h  63 

12.1	Appendix 1.: Pyraclostrobin Toxicology Requirements and Available
Studies for Food Uses	  PAGEREF _Toc191365852 \h  63 

12.2	Appendix 2.: Acute Toxicity Data on Pyraclostrobin Technical	 
PAGEREF _Toc191365853 \h  64 

12.3	Appendix 3.: Subchronic, Chronic and Other Toxicity Profile	 
PAGEREF _Toc191365854 \h  65 

 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),
cotton, 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), Pristine® Fungicide
(EPA Reg. No. 7969-199), Insignia® (EPA Reg. No. 7969-184), and BAS 500
ST (EPA File Symbol 7969-EUN).  Pristine® Fungicide (EPA Reg. No.
7969-199) is a dual active ingredient product containing pyraclostrobin
and boscalid.  Proposed uses/tolerances for boscalid are evaluated in a
separate assessment.

BASF Corporation submitted a petition (6F7105) requesting the
establishment of tolerances for the combined residues of the fungicide
pyraclostrobin and its desmethoxy metabolite, expressed as parent
compound, in/on the following commodities: oats grain at 1.0 ppm; oats,
hay at 17 ppm; oats, straw at 17 ppm; and oilseed, group 20 at 0.4 ppm.

Concurrently, BASF Corp. wishes to amend the product label for
Headline® Fungicide (EPA Reg. No. 7969-186), an EC formulation
containing 23.6% ai (2.09 lb/gal) pyraclostrobin, to add new foliar uses
on oats, canola, and flax.  Headline® Fungicide is proposed for foliar
applications at maximum seasonal rates of 0.39 lb ai/A for canola and
flax and 0.29 lb ai/A for oats.  Proposed applications may be made using
ground or aerial equipment.  The proposed pre-harvest intervals (PHI)
range from 21 days (oilseed crops) to the beginning of flowering stage
(oats).  In addition, the petitioner wishes to register a supplemental
label, BAS 500 ST (EPA File Symbol 7969-EUN), a 20% WDG formulation, for
seed treatment on oats, canola, and flax.  BAS 500 ST is proposed for
seed treatment at rates of 0.005-0.04 lb ai/100 lb seed.

BASF Corporation submitted a label amendment to add aerial application
to a variety of turf and ornamentals onto the Insignia label (EPA Reg.
No. 7969-184) at a proposed maximum application of 0.5 lb ai/acre and a
maximum seasonal of 3.0 lb ai/acre at 10 to 28-day intervals.

BASF Corporation submitted a supplemental label to add an in-furrow
spray application at planting for corn, soybean and sugar beet onto the
Headline® label (EPA Reg. No. 7969-186) at 0.2 lb ai/acre.

IR-4 submitted a petition (6E7165) requesting the establishment of
pyraclostrobin tolerances, expressed as parent per se, in/on the
following commodities: herb subgroup 19A, fresh herb at 30.0 ppm; and
tropical fruits each at 0.7 ppm (avocado; black sapote; canistel; mamey
sapote; mango; papaya; sapodilla; and star apple).  Concurrent with the
tolerances proposed above, IR-4 wishes to amend the product label for
Pristine® Fungicide (EPA Reg. No. 7969-199) to incorporate new uses on
avocado, black sapote, canistel, mamey sapote, mango, papaya, sapodilla,
star apple, and fresh herbs.  Pristine® Fungicide is a WDG formulation
containing multiple active ingredients of pyraclostrobin (12.8%) and
boscalid (25.2%).  The product is proposed for two foliar applications
at a 7 or greater day interval on the above crops at rates up to 0.15 lb
ai/A with a 0-day PHI.

IR-4 submitted another petition (7E7245) requesting the establishment of
tolerances for the combined residues of the fungicide pyraclostrobin and
its desmethoxy metabolite, expressed as parent compound, in/on barley,
grain at 1.3 ppm and barley, straw at 9.0 ppm.  Concurrently, IR-4
wishes to amend the product label for Headline® Fungicide (EPA Reg. No.
7969-186) to revise the barley PHI from “apply no later than 50% head
emergence (Feekes 10.3, Zadok’s 55)” to 14 days.  The maximum
seasonal rate of 0.29 lb ai/A remains the same.

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 the use of pyraclostrobin.

Hazard Assessment and Dose Response

The quality of the toxicology database for pyraclostrobin is good and
the confidence in the hazard and dose-response assessments is high.  The
toxicity database for pyraclostrobin is considered complete, and deemed
adequate for endpoint selection for exposure risk assessment scenarios
and for FQPA evaluation.  Please refer to Appendix A for the toxicity
profile tables.  Please also refer to the previous pyraclostrobin risk
assessment document for further extensive details (B. O’Keefe, DP
Barcode 343700, 9/7/07).  The last risk assessment document included an
updated toxicology and hazard evaluation, including results of recently
submitted toxicity studies, a new carcinogenicity evaluation, and
selection of new study/endpoints for exposure by the inhalation route. 
As there are no new toxicity data associated with these current actions,
the hazard characterization and endpoint selection from the previous
risk assessment are applied directly to this action.

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, 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.

  SEQ CHAPTER \h \r 1 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.

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 was 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 points of
departure (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 toxicity data base for pyraclostrobin is adequate for evaluation of
the FQPA safety factor.  The following acceptable studies are available:
1) developmental toxicity studies in rats and rabbits; and 2) a
two-generation reproduction study in rats.  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.  Based on these data and conclusions, the FQPA
Safety Factor can be reduced to 1X.

Drinking Water Exposure Estimates

The Environmental Fate and Effects Division (EFED) reviewed the proposed
use rates associated with the Section 3 amended registration requests
for the use of pyraclostrobin on oats and oilseed crops (canola and
flax), fresh herbs (crop group 19), and tropical fruits (avocado, black
sapote, canistel, mamey sapote, mango, papaya, sapodilla, and star
apple).  Additionally, EFED reviewed the proposal to add aerial
applications to existing turf and ornamentals use sites and the proposal
to add in-furrow use to the existing corn, soybean, and sugar beets use
sites.

This drinking water exposure assessment was based on the application of
the highest seasonal use rate (proposed or registered) of
pyraclostrobin, i.e., the aerial application on turf and ornamentals at
0.5 lbs a.i./acre with 6 maximum seasonal applications at 14 day
intervals.  For surface water, a Tier II drinking water assessment was
performed using the PRZM/EXAMS models with index reservoir (IR)
scenarios and percent cropped area (PCA) adjustment factors. 
Concentrations of pyraclostrobin in surface water are not likely to
exceed 35.6 µg/L for the peak concentration, 2.3 µg/L for the annual
average concentration, and 1.5 µg/L for the 30 year average
concentration.

Ground water concentrations were estimated using a Tier I SCI-GROW,
which 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
residues from crop field trials were used.  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 from pyraclostrobin processing studies 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 80% 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 contribute to
aggregate exposures.  Residential and recreational turf applications are
applied by professional pest control operators (PCOs) only, and
therefore, residential handler exposures do not occur.  There is,
however, a potential for exposure to homeowners in residential settings
from entering previously treated lawns where children might play and
adults might work or play.  As a result, risk assessments have been
completed for postapplication scenarios.  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 were conducted for acute and chronic dietary (food
+ drinking water) exposures.  Additionally, short- and intermediate-term
aggregate risk assessments were conducted.  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 toddlers 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
200, 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

No chemical-specific handler exposure data were submitted in support of
these registrations.  For the assessment of the foliar and in-furrow
uses, data from the Pesticide Handlers Exposure Database (PHED) Version
1.1 as presented in PHED Surrogate Exposure Guide (8/98) were used.  For
assessing seed treatment activities, exposure data were taken from HED
Science Advisory Council for Exposure Policy 14: Standard Operating
Procedures for Seed Treatment and HED Science Advisory Council for
Exposure Standard Operating Procedure 15: Amount of Seed Treated or
Planted per Day.

Results from the assessment of all occupational handler scenarios
indicate that risks are not of concern with baseline clothing, or in
some cases, when gloves and respirator are used to mitigate exposure. 
For foliar treatments, gloves were added for scenarios involving
mixing/loading liquids, and a dust/mist respirator was necessary
specifically for the oats use scenario in order to reach an MOE of 100
or greater.  For seed treatment activities, gloves were needed for
several scenarios, with the addition of a dust/mist respirator for the
scenario designated “multiple activity”. 

The proposed Headline® Fungicide label requires chemical resistant
gloves, however, a respirator is not indicated.  The proposed BAS 500 ST
label is a supplemental label only, and does not provide information
regarding personal protective equipment (PPE).

Occupational Postapplication Exposure Assessment

Previously submitted chemical-specific dislodgeable foliar residue (DFR)
data and the interim transfer coefficient policy developed by HED’s
Science Advisory Council for Exposure, which includes proprietary data
from the Agricultural Re-entry Task Force (ARTF) database (policy #
3.1), was used in estimating postapplication exposures.

The results of the postapplication exposure and risk assessment indicate
that MOEs of 100 are achieved on Day 0 for all scenarios.  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.  The proposed labels indicate an REI
of 12 hrs, which is in compliance with the WPS.

Recommendations for Tolerances

HED has completed a human health risk assessment for the proposed new
uses of the active ingredient pyraclostrobin.  

For Petition #6F7105 - Provided that a revised label is submitted that
specifies the appropriate 14-day plantback interval restriction for all
annual crops that are not registered and a revised Section F is
submitted reflecting the recommended tolerances and commodity
definitions presented in Table 14, the residue chemistry, toxicological,
and occupational databases support the acceptance of a conditional
registration on oats, canola, and flax, and establishment of permanent
tolerances for pyraclostrobin residues of concern in/on the following
raw agricultural commodities: 

Oat, grain	1.2 ppm

Oat, hay	18 ppm

Oat, straw	15 ppm

Borage, Crambe, Cuphea, Echium, Flax seed, Gold of pleasure, Hare’s
ear mustard, Lesquerella, Lunaria, Meadowfoam, Milkweed, Mustard seed,
Oil radish, Poppy seed, Rapeseed, Sesame, Sweet rocket (rapeseed
subgroup)	0.45 ppm

Castor oil plant, Chinese tallowtree, Euphorbia, Evening primrose,
Jojoba, Niger seed, Rose hip, Safflower, Stokes aster, Sunflower,
Tallowwood, Tea oil plant, Vernonia (sunflower subgroup)	0.45 ppm

Cotton (cotton subgroup)	0.45 ppm

The petitioner should submit a revised Section F to propose individual
tolerances of 0.45 ppm for all oilseeds in subgroups rapeseed,
sunflower, and cotton, as follows: 1) rapeseed (i.e., borage, crambe,
cuphea, echium, flax seed, gold of pleasure, hare’s ear mustard,
lesquerella, lunaria, meadowfoam, milkweed, mustard seed, oil radish,
poppy seed, rapeseed, sesame, and sweet rocket); 2) sunflower (i.e., 
Castor oil plant, Chinese tallowtree, Euphorbia, Evening primrose,
Jojoba, Niger seed, Rose hip, Safflower, Stokes aster, Sunflower,
Tallowwood, Tea oil plant, Vernonia ); and 3) cotton (only entry
presently in this subgroup).

Note: The existing tolerances on sunflower at 0.3 ppm and cotton,
undelinted seed at 0.3 ppm should be removed from 40 CFR §180.582.

For Petition #7E7245 - Provided that a revised label is submitted that
specifies the appropriate 14-day plantback interval restriction for all
annual crops that are not registered and a revised Section F is
submitted reflecting the recommended tolerances and commodity
definitions presented in Table 14, the residue chemistry, toxicological,
and occupational databases support the proposed amended use pattern for
barley and permanent tolerances for pyraclostrobin residues of concern
in/on the following raw agricultural commodities: 

Barley, grain	1.4 ppm

Barley, straw	6.0 ppm

For Petition #6E7165 – Provided that a revised label is submitted that
specifies the appropriate 14-day plantback interval restriction for all
annual crops that are not registered and a revised Section F is
submitted, the residue chemistry, toxicological, and occupational
databases support the establishment of a conditional registration on
avocados, black sapote, canistel, mamey sapote, mango, papaya,
sapodilla, and star apple, and permanent tolerances for pyraclostrobin
residues of concern in/on the following raw agricultural commodities:

Avocado	0.6 ppm

Sapote, black	0.6 ppm

Canistel	0.6 ppm

Sapote, mamey	0.6 ppm

Mango	0.6 ppm

Papaya	0.6 ppm

Sapodilla	0.6 ppm

Star Apple	0.6 ppm

Note:  HED is in the process of revising the Commodity Definitions
listed under 40 CFR §180.1(h) to make the tropical/subtropical fruit
avocado a general commodity; see same 6/14/06 memo by B. Schneider.  The
specific commodities included in the general definition for avocado
include black sapote, canistel, mamey sapote, mango, papaya, sapodilla,
and star apple.  Until the regulations have been finalized in the
Federal Register, separate tolerances are needed for each specific
commodity, at the same level as the respective general commodity
tolerance.

A withdrawal letter for withdrawal of the fresh herbs section of
petition #6E7165 was recently received by OPP from IR-4 (2/6/08). 
Therefore, at this time HED is not recommending for tolerances on any
herbs in the Herbs subgroup 19A. 

The petitioner should submit a revised Section F to correct the
tolerance residue definition (parent + metabolite) and to make it
consistent with the definition listed in 40 CFR §180.582 (a)(1).  The
revised Section F should also incorporate the recommended tolerances and
commodity definitions presented in Table 14.

Recommendations for Field Residue Data

860.1500 Crop Field Trials

The submitted residue data for avocado are inadequate to fulfill data
requirements because the field trials were conducted at exaggerated
rates (ca 2.6x).  Since the submitted data represent an overestimate of
the residues expected from the proposed use, HED considers that the
tolerance for avocado may need to be reduced.  Also, since the proposed
use is for late season foliar application, includes a 0-day preharvest
interval, and these data are being translated to support a wide number
of tropical/subtropical fruits, HED requests that the petitioner provide
additional, bridging field trial data (i.e., two to three field trials
at the proposed label rate of 2 applications, total 0.3 lb ai/season) as
a condition of registration.

Recommendations for Labels

The proposed Headline® Fungicide label requires chemical resistant
gloves; however, a respirator is not indicated and is needed for the
handler scenario of mixing/loading liquids for aerial application or
chemigation.  

The proposed BAS 500 ST label is a supplemental label only, and does not
provide information regarding personal protective equipment (PPE).  Such
PPE information should be added to the label.  Gloves are needed for
several seed treatment scenarios, and a respirator is needed for the
multiple activity scenario.

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 relies in part on data from Pesticide Handlers
Exposure Database (PHED) studies in which adult human subjects were
intentionally exposed to a pesticide or other chemical.  These studies
have been determined to require a review of their ethical conduct, have
received that review, and have been determined to be ethical.

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),
cotton, 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.  

A summary of the pyraclostrobin end-use products and proposed crop use
patterns discussed in this document is listed in Table 1.  No rotational
crop restrictions are listed on the product labels.

Table 1.  Summary of Proposed Directions for Use of Pyraclostrobin.

Applic. Timing, Type, and Equip. 	Formulation

[EPA Reg. No.]	Applic. Rate 

(lb ai/A)	Max. No. Applic. per Season	Max. Seasonal Applic. Rate

(lb ai/A)	PHI

(days)	Use Directions and Limitations

Fresh Herbs (including Angelica, Balm, Basil, Borage, Burnet, Chamomile,
Catnip, Chervil, Chive, Chinese Chive, Clary, Coriander (leaf),
Costmary, Cilantro (leaf), Curry (leaf), Dillweed (fresh and for
processing into oil), Horehound, Hyssop, Lavender, Lemongrass, Lovage
(leaf), Marigold, Marjoram (Origanum spp.), Nasturtium, Parsley,
Pennyroyal, Rosemary, Rue, Sage, Summer Savory, Winter Savory, Sweet
Bay, Tansy, Tarragon, Thyme, Wintergreen, Woodruff, and Wormwood)

Foliar

Ground, aerial or through sprinkler irrigation	Pristine® Fungicide

12.8% WDG

[7969-199]	0.08 - 0.15	2	0.30	0	Begin applications prior to the onset of
disease development and repeat applications 7 days later as needed, or
alternate with another registered fungicide having a different mode of
action.

Avocado, Black Sapote, Canistel, Mamey Sapote, Mango, Papaya, Sapodilla,
and Star Apple

Foliar

Ground, aerial or through sprinkler irrigation	Pristine® Fungicide

12.8% WDG

[7969-199]	0.15	2	0.30	0	Begin application prior to the onset of disease
development and repeat applications 7 days later as needed, or alternate
with another registered fungicide having a different mode of action.

Canola and Flax

Foliar

Ground, aerial or through sprinkler irrigation	Headline® Fungicide

23.6% EC

(2.09 lb/gal)

[7969-186]	0.10	Not specified	0.39	21	Begin applications prior to
disease development, and continue on a 7- to 14-day interval if
conditions are conducive for disease development.  To limit the
potential for development of resistance, do not make more than one
application before alternating to a fungicide with a different mode of
action.  May be used with adjuvants.

Seed treatment	BAS 500 ST

20% WDG

[7969-EUN]	0.02-0.04 lb ai/100 lb of seed	1	0.04 lb ai/100 lb of seed
N/A	For control of seed and seedling disease caused by Pythium spp. on
black mustard, crambe, field mustard, flax, Indian mustard, Indian
rapeseed, rapeseed (canola), safflower, and sunflower, apply only in
conjunction with registered rates of mefenoxam- or metalaxyl-containing
seed treatment products.

Oats

Foliar

Ground, aerial or through sprinkler irrigation	Headline® Fungicide

23.6% EC

(2.09 lb/gal) 

[7969-186]	0.15	2	0.29	14 (hay or feed green-chopped oats)	Begin
applications prior to disease development, immediately after flag leaf
emergence.  Apply no later than the beginning of flowering (Feeke’s
10.5.to Zadok’s 59) stage.  May be used with adjuvants.

Seed treatment	20% WDG

[7969-EUN]	0.005-0.01 lb ai/100 lb of seed	1	0.01 lb ai/100 lb of seed
N/A

	Barley

Foliar

Ground, aerial or through sprinkler irrigation	Headline® Fungicide

23.6% EC

(2.09 lb/gal) 

[7969-186]	0.15	2	0.29	14 (hay or feed green-chopped barley)	Use limited
to the following states:  AZ, CO, ID, MT, NV, NM, OR, TX, UT, WA, and
WY.  Begin applications prior to disease development, immediately after
flag leaf emergence.  Apply no later than 50% head emergence (Feeke’s
10.3.to Zadok’s 55) stage.  May be used with adjuvants.

Corn, Soybean and Sugar beet

In-Furrow	Headline® Fungicide 23.6% EC

(2.09 lb/gal) 

[7969-186]	0.20	1	0.20	N/A	Apply at planting as an in-furrow application
by directing the spray into the furrow before seed is covered.  Use a
minimum volume of 2.5 gal water per acre.

Turf and Ornamentals

Foliar

Aerial application	Insignia® Fungicide 

20% WDG

[7969-184]	0.28 - 0.5

3.0	N/A	For aerial application, apply in no less than 10 gallons of
spray solution per acre.  Repeat at 10- to 28-day intervals, depending
on disease.  Do not apply more than 2 sequential applications.  No
aerial application in New York state except as permitted under FIFRA
Section 24(c).

Conclusions.  The field trial data for herbs subgroup 19A and tropical
fruits do not reflect the proposed use patterns since they were
conducted at exaggerated rates.  Additional bridging field trial residue
data are required to reflect the proposed label rates.  In addition,
label revision is required to specify appropriate rotational crop
restrictions.  Details of label revisions are incorporated in the
respective crop section.

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

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; = Kow 4.18, pH 6.5).

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

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 

The quality of the toxicology database for pyraclostrobin is good and
the confidence in the hazard and dose-response assessments is high.  The
toxicity database for pyraclostrobin is considered complete, and deemed
adequate for endpoint selection for exposure risk assessment scenarios
and for FQPA evaluation.

The most recent risk assessment included an updated toxicology and
hazard evaluation, including results of recently submitted toxicity
studies, a new carcinogenicity evaluation, and selection of new
study/endpoints for exposure by the inhalation route.  Please refer to
this previous pyraclostrobin risk assessment document for further
extensive details (B. O’Keefe, DP Barcode 343700, 9/7/07).  Also,
please refer to Appendices 2 and 3 of this current risk assessment
document for the toxicity profile tables.  As there are no new toxicity
data associated with these current actions, the hazard characterization
and endpoint selection, from the previous risk assessment are applied
directly to this action.

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.

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 2).

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.

Other findings in the rat and mouse 90-day studies included
hematopoietic toxicity.  In rats, the hematopoietic effects included
mild hemolytic anemia accompanied by increased reticulocytes, increased
spleen weight, spleen microscopic changes, and increased total
leukocytes, neutrophils, 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 includes 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:  The Cancer Assessment Review Committee (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).

3.1.3	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 was 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 points of
departure (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 point of departure 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 factor of 14% will be applied to the dermal
long-term risk scenario.

The short-, intermediate-, and long-term inhalation endpoints are from
the 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.

The short- and intermediate-term incidental oral endpoints are from the
13-week feeding study in dogs.  The NOAEL of 5.8 mg/kg/day is 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).  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). 

3.2	FQPA Safety Factor for Infants and Children  TC \l2 "3.2	Safety
Factor for Infants and Children 

The toxicity data base for pyraclostrobin is adequate for evaluation of
the FQPA safety factor.  The following acceptable studies are available:
1) developmental toxicity studies in rats and rabbits; and 2) a
two-generation reproduction study in rats.  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.

3.3	Summary of Toxicological Doses and Endpoints for Use in Human Health
Risk Assessments  TC \l2 "3.3	Summary of Toxicological Doses and
Endpoints for Use in Human Health Risk Assessments 

HED recently completed a Section 3 human health risk assessment for the
use of pyraclostrobin on cotton and Belgian endive (Memo B. O’Keefe,
et. al., 9/7/07, DP# 343700).  As there are no new toxicity data
associated with this current action, the hazard characterization and
endpoint selection, from the previous risk assessment are applied
directly to this action.  All previous exposure risk assessments remain
unchanged.  Below are the up-to-date tables.  

Table 2. 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 3.  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.



3.4	Recommendation for Aggregate Exposure Risk Assessments  TC \l2 "3.4
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 for adults and
toddlers were 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. 

3.5	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	Public Health and Pesticide Epidemiology Data   TC \l1 "4.0	Public
Health and Epidemiology Data 

The Centers for Disease Control (CDC) and Prevention recently reported
and described five incident events to the Iowa Department of Public
Health (IDPH) of exposures that occurred during aerial applications of
pyraclostrobin (MMWR Weekly, 2/4/08, 56(51) pp.1343-1345).  IDPH
investigated the reports.  In one event migrant workers were
inadvertently exposed to pyraclostrobin due to pilot error and
off-target drift of pyraclostrobin to an adjacent field.  The migrant
workers experienced symptoms including upper respiratory tract pain or
irritation, chest pain, nausea, skin redness, eye pain, weakness,
headache, and dizziness.  In another event, a crop-dusting pilot
suffered first degree burns after being exposed to pyraclostrobin which
had spilled after his airplane crashed during takeoff.  Another three
events also involved acute pesticide poisoning associated with
off-target drift of pyraclostrobin from nearby aerial applications.  In
all five of these cases, symptoms subsided after the exposed persons
moved indoors or away from the pyraclostrobin treated fields.

Pyraclostrobin labels that permit aerial applications contain specific
label language stating not to apply under circumstances where possible
drift may occur and how to reduce drift potential.

5.0	Dietary Exposure/Risk Characterization  TC \l1 "5.0	Dietary
Exposure/Risk Characterization 

Reference: Pyraclostrobin.  Petitions for the Establishment of Permanent
Tolerances on:  (i) Oat Grain, Hay, and Straw, and Oilseed (Crop Group
20) - PP#6F7105; (ii) Fresh Herbs (Herbs Subgroup 19A), Avocado, Black
Sapote, Canistel, Mamey Sapote, Mango, Papaya, Sapodilla, and Star Apple
- PP#6E7165; and (iii) Barley Grain and Straw- PP#7E7245.  Summary of
Analytical Chemistry and Residue Data. DP Numbesr 345965, 348700 &
343754; J. Stokes; 02/12/08.

5.1	Pesticide Metabolism and Environmental Degradation  TC \l2 "5.1 
Pesticide Metabolism and Environmental Degradation 

5.1.1	Metabolism in Primary Crops  TC \l3 "5.1.1	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).



5.1.2	Metabolism in Livestock  TC \l3 "5.1.2	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).

5.1.3	Analytical Methodology  TC \l3 "5.1.3	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 of raw agricultural and processed commodities from the current
crop field trials 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)).  Briefly, residues were extracted by
shaking with methanol:water:2 N HCl (70:25:5; v:v:v) and centrifuged. 
Residues were then partitioned with cyclohexane, concentrated to
dryness, and re-dissolved in buffered methanol:water (80:20, v:v).  The
final chromatographic analysis of residues was determined by LC/MS/MS. 
Total residues of pyraclostrobin and BF 500-3 are expressed as
pyraclostrobin equivalents.  For each analyte, the validated method LOQ
is 0.02 ppm, and the estimated LODs are 0.003-0.03 ppm.  The method is
adequate for data collection based on acceptable concurrent method
recovery data.

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.

500-3 are relatively stable at ≤-10ºC in fortified samples of grape
juice (juices), sugar beet tops (leafy vegetables), sugar beet roots
(root crop), tomato (fruit/fruiting vegetable), 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.  There are adequate storage stability data from PP#0F6139
which may be translated in the current petitions to validate sample
storage conditions and durations.  There are no corrections which need
to be applied as pyraclostrobin residues of concern were found to be
relatively stable over a wide range of commodities under frozen storage
conditions for 19-25 months.

5.1.5	Magnitude of the Residue in Plants  TC \l3 "5.1.5	Magnitude of the
Residue in Plants 

The field trials conducted on fresh herbs (basil, chives, and dill) and
avocados included a tank mixture of the pyraclostrobin test formulation
(BAS 500 02F) with another active ingredient, boscalid (formulated as
BAS 510 UCF).  The field trials conducted on oats also reflect a tank
mixture with metconazole (formulated as BAS 555 01F).  Only the residue
data from treatments with pyraclostrobin are reported in this risk
assessment.



Field Trial Data Submitted Under PP#6F7105

Canola -DER Reference:  46925301.der.doc

BASF Corporation has submitted field trial data for pyraclostrobin on
canola.  A summary of residue data from the canola field trials is
presented in Table 4.  The residue decline data indicate that residues
of pyraclostrobin decrease at longer preharvest intervals.

Table 4.  Summary of Residue Data from Canola Field Trials with
Pyraclostrobin.

Commodity	Total Applic. Rate

(lb ai/A)	PHI (days)	Combined Residue Levels of Pyraclostrobin and its
Metabolite BF 500-3 (ppm)

	n	Min.	Max.	HAFT	Median

(STMdR)	Mean

(STMR)	Std. Dev.

Proposed use pattern:  Four foliar sprays at 0.10 lb ai/A/application
for a seasonal rate of 0.39 lb ai/A with a 21-day PHI.

Canola seed	0.39-0.41	20-22	32	<0.04	0.27	0.25	0.05	0.08	0.06

	0.20	21-22	10	<0.04	0.11	0.10	0.04	0.06	0.03

Conclusions:  The proposed use patterns of pyraclostrobin on canola and
flax include foliar and seed treatments.  The residue data included in
the canola field study only reflect foliar use, and no seed treatment
data were submitted.  Based on the seeding rate typically used for
canola (4-8 lb of seed per acre) and flax (28-84 lb of seed per acre),
the proposed maximum seed treatment rate of 0.04 lb ai/100 lb of seed
per acre would be equivalent to maximums of 0.012 lb ai/A for flax and
0.0032 lb ai/A for canola, which are negligible compared to the maximum
proposed seasonal rate of ~0.4 lb ai/A for foliar uses.

The submitted field trial data reflecting foliar uses for canola seed
are adequate.  The number and locations of field trials are in
accordance with OPPTS Guideline 860.1500, and the conducted field trials
reflect the maximum proposed foliar use pattern.

Oats - DER Reference:  46902226.der.doc

BASF Corporation has submitted field trial data for pyraclostrobin on
oats.  A summary of residue data from the oat field trials is presented
in Table 5.  The decline data show that pyraclostrobin residues remain
relatively constant in oat commodities with increasing preharvest
intervals.

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

Commodity	Total Applic. Rate

(lb ai/A)	PHI (days)	Combined Residue Levels of Pyraclostrobin and its
Metabolite BF 500-3 (ppm)

	n	Min.	Max.	HAFT	Median

(STMdR)	Mean

(STMR)	Std. Dev.

Proposed use pattern:  Two foliar sprays at 0.15 lb ai/A/application for
a seasonal rate of 0.3 lb ai/A.  The proposed PHIs are 14 days for hay
and green chopped oats (forage).  No PHIs are proposed for grain and
straw.

Grain	0.29-0.31	20-26	24	0.10	0.75	0.64	0.35	0.33	0.18

Straw

	24	1.33	14.90	13.40	3.92	4.70	3.07

Hay	0.29-0.31	6-8	24	2.38	14.83	14.46	6.00	6.25	3.20

Conclusions:  The proposed use patterns of pyraclostrobin on oats
include foliar and seed treatments.  The supporting residue data
included in the current petition only reflect foliar use, and no seed
treatment data were submitted.  Based on the seeding rate typically used
for oats (50-120 lb of seed per acre), the proposed seed treatment rate
of 0.005-0.01 lb ai/100 lb of seed per acre would be equivalent to
0.005-0.012 lb ai/A which is negligible compared to the maximum proposed
seasonal rate of ~0.3 lb ai/A for foliar use.

The submitted field trial data reflecting foliar uses for oat grain,
straw, and hay are adequate to fulfill data requirements pending
submission of revised Sections B and F.  Based on the available data, a
revised Section B is required to specify PHIs of 20-26 days for oat
grain and straw and 6-8 days for oat hay.  A revised Section F is
required to amend the proposed tolerances as determined by the
Agency’s tolerance spreadsheet.

Geographic representation of residue data for oat grain, straw, and hay
is not in full compliance with GLN 860.1500 requirements since only 12
trials were conducted; the guideline requires a total of 16 trials to
establish individual tolerances for oat commodities.  However, the
petitioner has included Appendix J in the study report which documents
correspondence between EPA and BASF regarding the “Proposal to EPA and
PMRA for Reduction of the Number of Field Residue Sites Required to Set
a Fungicide Tolerance in Small Grains (Wheat, Barley, Oats, and Rye)”.
 Based on the total number of field trials conducted for small grains,
it was reported that the conducted trials for oats should be adequate to
set individual tolerances on wheat, barley, oats, and rye.

No residue data are submitted for oat forage.  The petitioner did not
provide residue data or propose a tolerance for oat forage because
applications are made after the growth stages at which oat is foraged. 
Based on the current proposed use patterns, the Agency will not require
residue data or a tolerance for oat forage.

The field trial data for oat grain, straw, and hay were entered into the
Agency’s tolerance spreadsheet as specified by the Guidance for
Setting Pesticide Tolerances Based on Field Trial Data SOP to determine
appropriate tolerance levels.  The tolerance spreadsheet recommends
tolerances of 1.2 ppm for oat grain, 15 ppm for oat straw, and 18 ppm
for hay.  These recommended levels vary slightly from the petitioner’s
tolerance proposals of 1.0 ppm for oat grain and 17 ppm each for oat hay
and straw.

Field Trial Data Submitted Under PP#6E7165

Herbs subgroup 19A

Basil - DER Reference:  47014803.der.doc

IR-4 has submitted field trial data for pyraclostrobin on basil.  A
summary of residue data from the basil field trials is presented in
Table 6.  The processing of fresh basil to dried basil resulted in an
increase of total residues, and the calculated processing factors of
total residues ranged 4.6-9.0x with an average factor of 6.5x.

Table 6.  Summary of Residue Data from Basil Field Trials with
Pyraclostrobin.

Commodity	Total Applic. Rate

(lb ai/A)	PHI (days)	Combined Residue Levels of Pyraclostrobin and its
Metabolite BF 500-3 (ppm)

	n	Min.	Max.	HAFT	Median

(STMdR)	Mean

(STMR)	Std. Dev.

Proposed use pattern:  Two foliar sprays at 0.15 lb ai/A/application for
a seasonal rate of 0.3 lb ai/A with a 0-day PHI. 

Fresh basil	0.80-0.83	0	8	7.2	21.1	16.1	8.9	10.9	4.5

3-4	8	1.3	7.5	7.4	4.9	4.8	2.6

Dried basil

0	4	40.1	80.6	80.6	74.7	67.5	18.5

Chives - DER Reference:  47014802.der.doc

IR-4 has submitted field trial data for pyraclostrobin on chives.  A
summary of residue data from the chive field trials is presented in
Table 7.  

Table 7.  Summary of Residue Data from Chive Field Trials with
Pyraclostrobin.

Commodity	Total Applic. Rate

(lb ai/A)	PHI (days)	Combined Residue Levels of Pyraclostrobin and its
Metabolite BF 500-3 (ppm)

	n	Min.	Max.	HAFT	Median

(STMdR)	Mean

(STMR)	Std. Dev.

Proposed use pattern:  Two foliar sprays at 0.15 lb ai/A/application for
a seasonal rate of 0.3 lb ai/A with a 0-day PHI.

Chives	0.81-0.83	0	8	0.7	8.8	7.8	6.9	5.8	3.1

Dill - DER Reference:  47014801.der.doc

IR-4 has submitted field trial data for pyraclostrobin on dill.  A
summary of residue data from the dill field trials is presented in Table
8.

Table 8.  Summary of Residue Data from Dill Field Trials with
Pyraclostrobin.

Commodity	Total Applic. Rate

(lb ai/A)	PHI (days)	Combined Residue Levels of Pyraclostrobin and its
Metabolite BF 500-3 (ppm)

	n	Min.	Max.	HAFT	Median

(STMdR)	Mean

(STMR)	Std. Dev.

Proposed use pattern:  Two foliar sprays at 0.15 lb ai/A/application for
a seasonal rate of 0.3 lb ai/A with a 0-day PHI.

Fresh Dill	0.81-0.82	0	8	3.98	19.54	19.01	9.66	10.46	5.79

Dill Seed	0.80-0.83	0	6	3.60	22.60	21.20	18.30	14.45	8.34

Conclusions:  The submitted residue data for basil (fresh and dried) and
chives, the representative commodities of Herbs subgroup 19A, along with
those data submitted for dill (fresh and seed) are adequate with respect
to geographic representation of data.  However, the field trials were
conducted at an exaggerated total application rate of ~0.8 lb ai/A (2.7x
the maximum proposed seasonal rate of 0.3 lb ai/A).  As a result, these
data are not indicative of the magnitude of the residue following
applications at the proposed use pattern.

The petitioner has submitted a product label for Pristine® Fungicide
and this supplemental label directions state, “Do not apply more than
37 oz/A per season”, which equals 0.3 lb pyraclostrobin.  HED, at
times, allows a revised Section B to reflect this different rate. 
However, the proposed formulation contains two active ingredients, i.e.,
pyraclostrobin (12.8%) and boscalid (25.2%).  A review of the boscalid
data (See memo of 11/27/2007, C. Olinger), shows that boscalid was
applied only twice but by using a different formulation, for a total of
0.59 lb a.i./A.  This matches the proposed use rate for boscalid.  If
applied at the proposed label rate for pyraclostrobin (2
applications/season, 0.3 lb ai/A/season), then boscalid would be applied
at the proposed rate (2 applications/season, 0.58 lb ai/A/season). 
However, if this combined formulation is applied at the exaggerated rate
as representative of the submitted field trials, pyraclostrobin would be
applied at 0.8 lb/ai/A/season, while boscalid would be applied at 1.58
lb ai/A/season (2.7x).  Although the recommended pyraclostrobin
tolerance would cover any pyraclostrobin residues at four (4)
applications/season, boscalid residues at this treatment rate would
probably exceed the recommended tolerance for boscalid.  Thus, if it is
the intent of the petitioner to propose this combined formulation for
herbs (subgroup 19A), then a simple label revision will not solve the
problem.  The data only support two (2) applications of boscalid, and
not four (4) applications.  The proposed label cannot be revised to
match the submitted pyraclostrobin residue field trial data.  

Residue decline data were not submitted and are not required for the
purpose of this petition since GLN 860.1500 states that decline data
will typically not be required for each minor crop needing three or
fewer total trials to establish an individual tolerance.

The field trial data for all fresh herbs (basil, chives, and dill)
reflecting the exaggerated rate were entered into the Agency’s
tolerance spreadsheet as specified by the Guidance for Setting Pesticide
Tolerances Based on Field Trial Data SOP to determine an appropriate
tolerance level.  The tolerance spreadsheet recommends a tolerance of
25.0 ppm for Herbs subgroup 19A.  This tolerance level is slightly lower
than the level (30.0 ppm) initially proposed by the petitioner. 
Additional data from the basil and dill field trials suggest that
tolerances are needed for dried basil leaves at 85 ppm and dill seed at
25 ppm.  Based on the above discussion, this recommended tolerance would
be higher than needed when the proposed label directions (2
applications/season) are followed.

Avocado - DER Reference:  47014804.der.doc

IR-4 has submitted field trial data for pyraclostrobin on avocados.  A
summary of residue data from the avocado field trials is presented in
Table 9.

Table 9.  Summary of Residue Data from Avocado Field Trials with
Pyraclostrobin.

Commodity	Total Applic. Rate

(lb ai/A)	PHI (days)	Combined Residue Levels of Pyraclostrobin and its
Metabolite BF 500-3 (ppm)

	n	Min.	Max.	HAFT	Median

(STMdR)	Mean

(STMR)	Std. Dev.

Proposed use pattern:  Two foliar sprays at 0.15 lb ai/A/application for
a seasonal rate of 0.3 lb ai/A with a 0-day PHI.

Avocado	0.73-0.78	0	14	0.08	0.48	0.40	0.16	0.18	0.11

Conclusions:  The submitted residue data for avocado are inadequate to
fulfill data requirements because the field trials were conducted at
exaggerated rates.  Not only were the individual application rates
higher than the label maximum, but two additional applications beyond
what is specified on the label were applied, resulting in a seasonal
application rates ~2.5 – 2.7x the maximum proposed seasonal label
rate.  While the submitted data represent an overestimate of the
residues expected from the proposed use, the degree of exaggeration can
not be determined.  The use of the proportionality concept (See CHEMSAC,
minutes, 05/09/2007) to adjust residues downward is not considered
appropriate since the data included more applications than the desired
use.  Given that the proposed use is for late season foliar application,
and includes a 0-day preharvest interval, for the purpose of this IR-4
petition, HED will use the submitted data to support a tolerance for
avocado.  However, since HED considers that the tolerance may need to be
reduced, and further since this data is being translated to support a
wide number of tropical/subtropical fruits, HED requests that the
petitioner provide an additional two to three field trials at the label
rate (2 applications, total 0.3 lb ai/season) as a condition of
registration.  

The field trial data for avocado reflecting the exaggerated rate were
entered into the Agency’s tolerance spreadsheet as specified by the
Guidance for Setting Pesticide Tolerances Based on Field Trial Data SOP
to determine an appropriate tolerance level.  The tolerance spreadsheet
recommends a tolerance of 0.6 ppm for avocado which is slightly lower
than the level (0.7 ppm) initially proposed by the petitioner.

The submitted data for avocado may be translated to other tropical
fruits for which uses are proposed pending label revision as specified
above.  HED is in the process of revising the Commodity Definitions
listed under 40 CFR §180.1(h) to make the tropical/subtropical fruit
avocado a general commodity; see 6/14/06 memo by B. Schneider entitled
“Reviewer’s Guide and Summary of HED ChemSAC Approvals for Amending
Crop Groups/Subgroups [40 CFR §180.41] and Commodity Definitions [40
CFR §180.1(h)]”.  The specific commodities included in the general
definition for avocado include black sapote, canistel, mamey sapote,
mango, papaya, sapodilla, and star apple.  Until the regulations have
been finalized in the Federal Register, separate tolerances are needed
for each specific commodity, at the same level as the respective general
commodity tolerance.  Therefore, the petitioner is required to submit a
revised Section F to propose a tolerance of 0.6 ppm for each of the
following commodities: avocado, black sapote, canistel, mamey sapote,
mango, papaya, sapodilla, and star apple.

Field Trial Data Submitted Under PP#7E7245

Barley - DER Reference List	47190501.der.doc

IR-4 has submitted field trial data for pyraclostrobin on barley.  A
summary of residue data from the barley field trials is presented in
Table 10.

Table 10.  Summary of Residue Data from Barley Field Trials with
Pyraclostrobin

Commodity	Total Applic. Rate

(lb ai/A)	PHI (days)	Combined Residue Levels of Pyraclostrobin and its
Metabolite BF 500-3 (ppm)

	n	Min.	Max.	HAFT	Median

(STMdR)	Mean

(STMR)	Std. Dev.

Proposed use pattern:  Two foliar sprays at 0.15 lb ai/A/application for
a seasonal rate of 0.3 lb ai/A with a 14-day PHI.

Grain	0.29-0.30	14-15	8	0.54	0.98	0.93	0.85	0.80	0.16

Straw

	8	1.7	4.0	3.8	2.8	2.7	0.79

Grain	0.29-0.30	21-23	8	0.11	0.49	0.45	0.39	0.34	0.14

Straw

	8	0.65	2.2	1.8	1.4	1.3	0.50

Conclusions:  The submitted field trial data for barley grain and straw
are adequate to fulfill data requirements pending submission of a
revised Section F to amend the proposed tolerances as determined by the
Agency’s tolerance spreadsheet.

Geographic representation of residue data for barley grain and straw are
adequate.  No residue data were submitted for barley forage, and these
data are normally required to support the amended use pattern.  
However, the petitioner did not provide residue data or propose a
tolerance for barley hay because applications are made after the growth
stages at which barley hay is harvested.  Based on the current proposed
use patterns, the Agency will not require residue data or a tolerance
for barley hay.  

The field trial data for barley grain and straw were entered into the
Agency’s tolerance spreadsheet as specified by the Guidance for
Setting Pesticide Tolerances Based on Field Trial Data SOP to determine
appropriate tolerance levels.  The tolerance spreadsheet recommends
tolerances of 1.4 ppm for barley grain and 6.0 ppm for barley straw. 
These recommended levels vary slightly from the petitioner’s tolerance
proposals of 1.3 ppm for barley grain and 9.0 ppm for barley straw.

Amended Registration Request for At Planting Use on Corn, Soybean &
Sugar Beet

BASF Corporation submitted a supplemental label to add an in-furrow
spray application at planting for corn, soybean and sugar beet onto the
Headline® label (EPA Reg. No. 7969-186) at 0.2 lb ai/acre and a maximum
seasonal of 0.29 lb ai/acre.  Currently, Headline® is registered for
foliar use on corn, soybean and sugar beet.  No residue data reflecting
in-furrow at planting applications were submitted.  However, based on
the confined accumulation studies in rotational crops and field
rotational crop studies, HED determined (DP Barcode 340585, L. Cheng,
9/13/07) that the established tolerances in/on corn, soybean and sugar
beet commodities will be adequate to cover the proposed supplemental use
pattern and no new residue data are needed.

5.1.6	Magnitude of the Residue in Processed Food/Feed  TC \l3 "5.1.6
Magnitude of the Residue in Processed Food/Feed 

Basil - Residue data on dried basil leaves are included and summarized
in the Magnitude of the Residue section for fresh basil.

Barley - No residue data for the barley processed commodities (bran and
pearled) are submitted.  However, data from the wheat processing studies
(MRID #’s 45118620 and 45321101) can be translated to adequately
support the proposed use on barley.  Based on the wheat studies,
residues are not expected to concentrate in barley processed
commodities.

Canola - DER Reference:  46925301.de1.doc

BASF Corporation has   SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1
submitted a processing study with pyraclostrobin on canola.  A summary
of residue data from the canola processing study is presented in Table
11.  The results indicate that the combined residues of pyraclostrobin
and its metabolite BF 500-3 averaged 0.05 ppm in/on canola seed treated
at a total rate of 1.2 lb ai/A.  Following processing, combined residues
were <0.04 ppm in meal and 0.06 ppm in refined oil.  The equivalent
processing factors from these data are 0.8x for meal and 1.2x for
refined oil.  The maximum theoretical concentration factors for canola
processed commodities, based on separation into components, are 1.9x for
meal and 3.0x for oil (OPPTS GLN 860.1520, Table 3).



Table 11.  Residue Data from Canola Processing Study with
Pyraclostrobin.

RAC	Processed Commodity	Total Rate

(lb ai/A)	PHI 

(days)	Combined Residues of Pyraclostrobin and its BF 500-3 Metabolite
(ppm)	Processing

Factor

Pyraclostrobin	BF-500-3	Combined

	Canola seed	Seed	1.2	21	0.02, 0.03	<0.02, <0.02	<0.04, 0.05	--

	Meal

	<0.02, 0.03	<0.02, <0.02	<0.04, <0.04	0.8x

	Refined oil

	0.04, 0.04	0.02, 0.03	0.05, 0.07	1.2x

Conclusions:  The canola processing study is acceptable to satisfy data
requirements.  The treated samples of canola seed (RAC) used for
processing bore average combined residues of 0.05 ppm.  Following
processing of the RAC, total residues concentrated marginally in refined
oil (1.2x) but reduced in meal (0.8x).  The maximum expected combined
residues in refined oil, resulting from the proposed use, is 0.3 ppm. 
This value was calculated by multiplying the processing factor of 1.2x
by the HAFT residue of 0.25 ppm (see Table 4).  The maximum expected
residue in refined oil is identical to the recommended tolerance for the
RAC (canola seed).  Based on this determination, tolerances need not be
established for the processed commodities of canola.

Oat - No residue data for the oat processed commodities (flour and
groats/rolled oats) are submitted.  However, data from the wheat
processing studies (MRID #’s 45118620 and 45321101) can be translated
to adequately support the proposed use on oat.  Based on the wheat
studies, residues are not expected to concentrate in oat processed
commodities.

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

Livestock dietary burdens

The potential for secondary transfer of pyraclostrobin residues of
concern in meat, milk, poultry, and eggs exists because there are
several livestock feedstuffs (canola meal, oat grain, oat forage, oat
straw, and oat hay) that are associated with the proposed uses in the
current petitions.  The livestock dietary burdens of pyraclostrobin are
presented in Table 12, and reflect the most recent guidance from HED
concerning revisions of feedstuff percentages in Table 1 Feedstuffs
(October 2006) and constructing reasonably balanced livestock diets
(RBDs).  The calculated dietary burdens of pyraclostrobin are 4.7 for
beef cattle, 11.9 ppm for dairy cattle, 1.0 ppm for poultry, and 0.2 ppm
for swine.



Table 12.  Livestock Dietary Burdens for Pyraclostrobina.

	%  Diet b	Residue (ppm)

Feedstuff	Type	Tolerance,

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

almond hulls	R	1.6	90	-	5	-	-	-	0.89	-	-

barley, hay (oat, hay)	R	25 (18)	88	10	5 	-	-	2.8	2.8 (1.0)	-	-

corn, field, forage (silage)	R	5.0	40	-	30	-	-	-	3.8	-	-

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

legume, hay (cowpea)	R	25	30	-	5	-	-	-	4.2	-	-

barley, grain	CC	0.4	88	20	20	10	20	0.09	0.09	0.08	0.08

corn, field, grain	CC	0.1	88	50	20	-	65	0.057	0.023

0.065

oat, grain	CC	1.2	88	-	-	70	-	-	-	0.84	-

	

cotton, undelinted seed	PC	0.3	85	-	15	-	-	-	0.049	-	-

sunflower/canola (meal)	PC	0.3	92	15	-	20	15	0.049	-	0.06	0.045

Totals

100	100	100	100	4.7	11.9 (10.1)	1.0	0.2

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 10-15 %
 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 replacement
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.

Animal feeding studies

Residue Chemistry Memo, DP# 269668, 11/28/01, L. Cheng (PP#0F6139)

Adequate feeding studies were reviewed in PP#0F6139.  The current
pyraclostrobin tolerances for livestock commodities were established
based on results from these studies and the Agency’s estimated dietary
burdens for pyraclostrobin residues, which were originally calculated to
be 36.3 ppm for beef cattle, 35.4 ppm for dairy cattle, and 0.35 ppm for
poultry.

In the ruminant feeding study, dairy cows were dosed orally for 28 days
with pyraclostrobin at levels equivalent to 8.8 ppm (0.7x the
recalculated dietary burden), 27.2 ppm (2.3x), and 89.6 ppm (7.5x) in
their diet.  The study results from the 27.2 ppm-dose level were
reproduced from the initial petition review and are presented in below
Table 13.

  SEQ CHAPTER \h \r 1 

Table 13.  Residues of pyraclostrobin and its metabolites hydrolyzable
to BF 500-5 and BF 500-8 in milk and tissues from cows dosed twice daily
with pyraclostrobin at levels equivalent to 27.2 ppm for 28 consecutive
days.

Dosing or 

Sampling Day	Mid Dose (27.2 ppm)

	HPLC/UV Method 439	GC/MS (milk) Method 446/0 or LC/MS/MS (tissues)
Method 446/1

	Pyraclostrobin per se (ppm)	Residues hydrolyzable to BF 500-5, ppm
pyraclostrobin equivalents 1	Residues hydrolyzable to BF 500-8, ppm
pyraclostrobin equivalents 2	Total residues, ppm pyraclostrobin
equivalents 3

Whole Milk

1 	<0.01, <0.01, <0.01	<0.01, <0.01, <0.01	<0.01, <0.01, <0.01	<0.02,
<0.02, <0.02

4	--	<0.01, <0.01, <0.01	<0.01, <0.01, <0.01	<0.02, <0.02, <0.02

7	--	<0.01, <0.01, <0.01	<0.01, <0.01, 0.0124	<0.02, <0.02, <0.0224

10	--	<0.01, <0.01, <0.01	<0.01, <0.01, 0.011	<0.02, <0.02, <0.021

12	<0.01, <0.01, <0.01	<0.01, <0.01, <0.01	<0.01, <0.01, 0.0119	<0.02,
<0.02, <0.0219

15	--	<0.01, <0.01, <0.01	<0.01, 0.0126, 0.0135	<0.02, <0.0226, <0.0235

18	--	<0.01, <0.01, <0.01	<0.01, 0.0104, 0.0130	<0.02, <0.0204, <0.0230

21	--	<0.01, <0.01, <0.01	<0.01, <0.01, <0.01	<0.02, <0.02, <0.02

24	--	<0.01, <0.01, <0.01	<0.01, <0.01, <0.01	<0.02, <0.02, <0.02

27	<0.01, <0.01, <0.01	<0.01, <0.01, <0.01	<0.01, <0.01, 0.0108	<0.02,
<0.02, <0.0208

Skim Milk

26	<0.01, <0.01, <0.01	<0.01, <0.01, <0.01	<0.01, <0.01, <0.01	<0.02,
<0.02, <0.02

Milk Fat

26	<0.01, <0.01, <0.01	<0.01, <0.01, <0.01	<0.01, 0.0368, 0.0461	<0.02,
<0.0468, <0.0561

Fat

29	<0.05, <0.05, <0.05	<0.05, <0.05, <0.05	<0.05, <0.05, <0.05	<0.1,
<0.1, <0.1

Kidney

29	<0.05, <0.05, <0.05	<0.05, <0.05, <0.05	<0.05, <0.05, <0.05	<0.1,
<0.1, <0.1

Liver

29	<0.05, <0.05, <0.05	0.0645, 0.0761, 0.0973	0.399, 0.426, 0.510	0.464,
0.502, 0.607

Muscle

29	<0.05, <0.05, <0.05	<0.05, <0.05, <0.05	<0.05, <0.05, <0.05	<0.1,
<0.1, <0.1

1   Pyraclostrobin and its metabolites hydrolyzable to BF 500-5 were
determined in milk using the GC/MS method and in tissues using the
LC/MS/MS method. 

2   Metabolites hydrolyzable to BF 500-8 were determined in milk using
the GC/MS method and in tissues using the LC/MS/MS method.

3   Total BF 500-5 and BF 500-8 residues, expressed as pyraclostrobin
equivalents.

In the poultry feeding study, l  SEQ CHAPTER \h \r 1 aying hens were
orally dosed once daily for 30 consecutive days with pyraclostrobin at
dose levels equivalent to 0.28 ppm (0.3x), 0.88 ppm (1.1x), and 3.01 ppm
(3.0x).  At the highest feeding level of 3.01 ppm, residues of
pyraclostrobin and its metabolites hydrolyzable to BF 500-5 were less
than the method LOQ (0.05 ppm) in all egg and tissue samples, except for
one egg sample (Day 17) where residues of pyraclostrobin were detected
at 0.064 ppm and <0.05 ppm upon re-analysis.  Residue analysis of BF
500-8 was not conducted (the metabolism data show all metabolites
hydrolyzable to BF 500-8 would be less than 10% TRR), but instead an
isomeric compound (BF 500-9) was measured.  Levels of BF 500-9 also were
all <0.05 ppm.

Conclusions:  Based on these dietary exposure levels and the residue
data from the ruminant feeding study, the existing pyraclostrobin
tolerances for milk (0.1 ppm), meat (0.1 ppm), fat (0.1 ppm), meat
byproducts except liver (0.2 ppm), and liver (1.5 ppm) of cattle, goats,
hogs, horses, and sheep are adequate to support the proposed uses. 
Tolerances for eggs and poultry are not needed based on data from the
poultry feeding and metabolism studies [Category 180.6(a)(3)].  If in
the future, if a petitioner proposes a use which increases the dietary
burdens of poultry, then the Category 3 situation will be re-evaluated.

5.1.8	Confined and Field Rotational Accumulation in Rotational Crops  TC
\l3 "5.1.8	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.

5.1.9	Drinking Water Residue Profile TC \l3 "5.1.9	Drinking Water
Residue Profile 

Reference: Tier II Drinking Water Assessment for the use of
Pyraclostrobin (P.C. Code: 099100) on Oats and Oilseed (canola and flax)
(Headline Fungcide); Corn, Soybean, and Sugar beets (Headline Fungcide);
Fresh Herbs (crop group 19) and Tropical Fruits (avocado, black sapote,
canistel, mamey sapote, mango, papaya, sapodilla, and star apple)
(Pristine Fungicide); and Turf and Ornamentals (Insignia Fungicide) (DP
Barcodes 336190, 340588, 342584). G. Rothman, 9/6/07.

The Environmental Fate and Effects Division (EFED) reviewed the proposed
use rates associated with the Section 3 requests for the use of
pyraclostrobin on oats and oilseed crops (canola and flax), fresh herbs
(crop group 19), and tropical fruits (avocado, black sapote, canistel,
mamey sapote, mango, papaya, sapodilla, and star apple).  Additionally,
EFED reviewed the proposal to add aerial applications to existing turf
and ornamentals use sites and the proposal to add in-furrow use to the
existing corn, soybean, and sugar beets use sites.

This assessment was based on the application of the highest seasonal use
rate (proposed or registered) of pyraclostrobin.  The aerial application
on turf and ornamentals contains the highest seasonal application at 0.5
lbs a.i./acre with 6 maximum seasonal applications at 14 day intervals. 
The proposed use rate for the aerial application on turf and ornamentals
is the same as for the registered use of pyraclostrobin for ground
application on turf (please see the,“Environmental Fate and Ecological
Risk Assessment for the Registration of Pyraclostrobin”, submitted
February 6, 2002.).  However, EFED believes that the aerial use of
pyraclostrobin on turf and ornamentals will pose the upper-bound
concentrations in surface and ground water since spray drift increases
and application efficiency decreases in an aerial application technique.

Measures of exposure for pyraclostrobin in the drinking water assessment
were obtained through modeling efforts only, since national-scale
monitoring data were not identified. The Tier II drinking water
assessment was performed using the Tier II PRZM/EXAMS (PE4V01 perl shell
with PRZM 3.12 beta dated 5/24/01 and EXAMS version 2.98, 7/18/02) to
assess surface water.  Ground water concentrations were estimated using
a Tier I SCI-GROW model (version 2.3, May 16, 2006) since a Tier II
model has not been developed to assess ground water.

Acute effects of pyraclostrobin residues in drinking water are expressed
in annual peak one-in-ten year concentrations, chronic effects in annual
average one-in-ten year concentrations, and cancer effects in 30-year
average concentrations.  The upper-bound Tier II modeling predicts that
the concentrations of pyraclostrobin in surface water are not likely to
exceed 35.6 µg/L for the peak concentration, 2.3 µg/L for the annual
average concentration, and 1.5 µg/L for the 30-year average
concentrations.  The SCI-GROW model predicts the acute and chronic
concentrations of pyraclostrobin in shallow ground water to be 0.02 µg
/L (0.02 ppb).

5.1.10	Proposed Tolerances TC \l3 "5.1.10	Proposed Tolerances 

For purposes of both the tolerance expression and dietary risk
assessment, HED has concluded that the residues of concern in plant
commodities include pyraclostrobin and its desmethoxy metabolite, BF
500-3 (D278044, L. Cheng, 10/9/01), and the residues of concern in
livestock commodities include pyraclostrobin and its metabolites
convertible to 1-(4-chlorophenyl)-1H-pyrazol-3-ol (BF 500-5) and
1-(4-chloro-2-hydroxyphenyl)-1H-pyrazol-3-ol (BF 500-8).  

  SEQ CHAPTER \h \r 1 Pyraclostrobin tolerances for plant commodities
are listed in 40 CFR §180.582 (a)(1) and are expressed in terms of the
combined residues of the fungicide pyraclostrobin (carbamic acid,
[2-[[[1-(4-chlorophenyl)-1H- pyrazol-3-yl]oxy]methyl]phenyl]methoxy-,
methyl ester) and its desmethoxy metabolite (methyl
N-[[[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxy]methyl]phenyl carbamate),
expressed as parent compound.

Pyraclostrobin tolerances for animal commodities are listed in 40 CFR
§180.582 (a)(2) and are expressed in terms of the combined residues of
the fungicide pyraclostrobin and its metabolites convertible to
1-(4-chlorophenyl)-1H-pyrazol-3-ol and
1-(4-chloro-2-hydroxyphenyl)-1H-pyrazol-3-ol, expressed as parent
compound.

The tolerance expression proposed by BASF in PP#6F7105 is consistent
with the tolerance definition for plant commodities listed in 40 CFR
§180.582 (a)(1).  The tolerance expression proposed by IR-4 in
PP#6E7165 is expressed as pyraclostrobin per se and should be amended to
include all pyraclostrobin residues of concern.

The petitioner, BASF Corp., is currently proposing a crop group
tolerance of 0.4 ppm for “Oilseed, group 20”.  According to a
6/14/06 memo by B. Schneider entitled “Reviewer’s Guide and Summary
of HED ChemSAC Approvals for Amending Crop Groups/Subgroups [40 CFR
§180.41] and Commodity Definitions [40 CFR §180.1(h)]”, the new
Oilseed Crop Group 20 is being established to harmonize with Canada’s
Crop Group 20.  The representative commodities for the crop group are
rapeseed (canola varieties only) and sunflower seed.  Flax seed, for
which uses are being proposed as part of this petition, is a member of
this crop group.  The memo further states that until the Federal
Register Notice is published revising the Crop Group Regulation to
establish the Oilseed Crop Group 20, tolerances for the representative
commodities [rapeseed (canola seed) and sunflower seed] as well as all
members of the crop group will be listed individually, and the
tolerances will be identical.

The submitted residue data for canola seed are adequate and indicate
that the maximum combined residues were 0.27 ppm in/on samples treated
at 1x.  An individual pyraclostrobin tolerance for sunflower has already
been established at 0.3 ppm in 40 CFR §180.582.  Although adequate
residue data have been submitted and a tolerance of 0.3 ppm has been
established for sunflower seed, the other representative member of the
new Oilseed Crop Group 20, a crop group tolerance will not be
appropriate at this time until the Federal Register is issued revising
the Crop Group Regulation to establish the Oilseed Crop Group 20.  The
field trial data for canola seed were entered into the Agency’s
tolerance spreadsheet as specified by the Guidance for Setting Pesticide
Tolerances Based on Field Trial Data SOP to determine appropriate
tolerance levels.  The tolerance spreadsheet recommends a tolerance of
0.45 ppm for canola seed.  Based on the submitted field trial data, HED
is recommending individual tolerances of 0.45 ppm for all oilseeds in 3
subgroups:  1) rapeseed (i.e., borage, crambe, cuphea, echium, flax
seed, gold of pleasure, hare’s ear mustard, lesquerella, lunaria,
meadowfoam, milkweed, mustard seed, oil radish, poppy seed, rapeseed,
sesame, and sweet rocket); 2) sunflower (i.e.,  Castor oil plant,
Chinese tallowtree, Euphorbia, Evening primrose, Jojoba, Niger seed,
Rose hip, Safflower, Stokes aster, Sunflower, Tallowwood, Tea oil plant,
Vernonia );  3) cotton (only entry presently in this subgroup).  The
canola seed data will be translated to all oilseeds in the rapeseed
subgroup, and the sunflower data will be translated to all oilseeds in
the sunflower subgroup.  The petitioner is required to submit a revised
Section F to propose individual tolerances for all above oilseeds at
0.45 ppm each.  

The submitted field trial data for oat grain, straw, and hay are
adequate pending label revision to specify PHIs of 20-26 days for oat
grain and straw and 6-8 days for oat hay.  The field trial data for oat
grain, straw, and hay were entered into the Agency’s tolerance
spreadsheet as specified by the Guidance for Setting Pesticide
Tolerances Based on Field Trial Data SOP to determine appropriate
tolerance levels.  The tolerance spreadsheet recommends tolerances of
1.2 ppm for oat grain, 15 ppm for oat straw, and 18 ppm for hay.  The
petitioner did not provide residue data or propose a tolerance for oat
forage because applications are made after the growth stages at which
oat is foraged.  Based on the current proposed use patterns, the Agency
will not require residue data or a tolerance for oat forage.

The submitted field trial data for basil (fresh and dried) and chives,
the representative commodities of Herbs subgroup 19A, along with those
data submitted for dill (fresh and seed) are inadequate because the
trials were conducted at an exaggerated rate of ~0.8 lb ai/A (2.7x). 
The submitted data may, however, be used to support the recommended
subgroup tolerance.  The field trial data for all fresh herbs (basil,
chives, and dill) reflecting the exaggerated rate were entered into the
Agency’s tolerance spreadsheet to determine an appropriate tolerance
level.  The tolerance spreadsheet recommends a tolerance of 25.0 ppm for
Herbs subgroup 19A.  Additional data from the basil and dill field
trials suggest that tolerances are needed for dried basil leaves at 85
ppm and dill seed at 25 ppm.  However, a withdrawal letter for
withdrawal of the fresh herbs section of petition #6E7165 has recently
been received by OPP.  Therefore, at this time HED is not recommending
for tolerances on any herbs in the Herbs subgroup 19A.

The submitted field trial data for avocado are inadequate because the
trials were conducted at an exaggerated rate (~2.6x) and no residue
decline data were submitted.  The submitted data may, however, be used
to support the proposed tolerance for avocado. The field trial data for
avocado reflecting the exaggerated rate were entered into the Agency’s
tolerance spreadsheet to determine an appropriate tolerance level.  The
tolerance spreadsheet recommends a tolerance of 0.6 ppm for avocado. 
Because of the exaggerated rate, the recommended tolerance would
probably be higher than needed. 

The submitted data for avocado may be translated to other tropical
fruits (black sapote, canistel, mamey sapote, mango, papaya, sapodilla,
and star apple) for which uses are proposed pending label revisions. 
HED is in the process of revising the Commodity Definitions listed under
40 CFR §180.1(h) to make the tropical/subtropical fruit avocado a
general commodity.  The specific commodities included in the proposed
general definition for avocado include black sapote, canistel, mamey
sapote, mango, papaya, sapodilla, and star apple.  Until the regulations
have been finalized in the Federal Register, separate tolerances are
needed for each specific commodity, at the same level as the respective
general commodity tolerance.

The submitted field trial data for barley grain and straw are adequate. 
The field trial data for barley grain and straw were entered into the
Agency’s tolerance spreadsheet as specified by the Guidance for
Setting Pesticide Tolerances Based on Field Trial Data SOP to determine
appropriate tolerance levels.  The tolerance spreadsheet recommends
tolerances of 1.4 ppm for barley grain and 6.0 ppm for barley straw.  No
residue data were submitted for barley forage, and these data are
normally required to support the amended use pattern.  However, the
petitioner did not provide residue data or propose a tolerance for
barley hay because applications are made after the growth stages at
which barley hay is harvested.  Based on the current proposed use
patterns, the Agency will not require residue data or a tolerance for
barley hay.

An acceptable canola processing study has been submitted, and the
results suggest that no tolerances are required for the processed
commodities of canola.  An oat processing study is required to support
the proposed use on oats.

An acceptable limited field rotational crop study is available.  No
rotational crop tolerances are required pending label revision to
specify a plantback interval of 14 days for all annual crops that are
not registered.

Adequate cattle and poultry feeding studies are available.  The existing
pyraclostrobin tolerances for milk, meat, fat, meat byproducts except
liver, and liver of cattle, goats, hogs, horses, and sheep were
reassessed, and no adjustments are needed.  Tolerances for eggs and
poultry are not needed at this time based on data from the poultry
feeding and metabolism studies [Category 180.6(a)(3)]. 

The Codex Alimentarius Commission has established maximum residue limits
(MRLs) for residues of pyraclostrobin at 0.5 ppm for oats and at 0.05
ppm for papaya (see Appendix I).  The US tolerance level and residue
definition both differ from Codex.  There are no Canadian or Mexican
MRLs for pyraclostrobin for the crop commodities discussed in this
Summary Document.

A summary of the recommended tolerances for the crop commodities
discussed in this document is presented in Table 14.  The petitioner
should submit a revised Section F reflecting the recommended tolerances
and commodity definitions presented in Table 14.

Table 14.	Tolerance Summary for Pyraclostrobin.

Commodity	Proposed Tolerance (ppm)	Recommended Tolerance (ppm)	Comments;
Correct Commodity Definition

Tolerances Proposed Under PP#6E7105

Oats grain	1.0	1.2	Tolerance recommendations are tentative pending
submission of a revised Section B to specify PHIs of 20-26 days for oat
grain and straw and 6-8 days for oat hay.

Oat, grain; oat, hay, and oat straw.

Oats, hay	17	18

	Oats, straw	17	15

	Oilseed, group 20	0.4	Canola, seed at 0.45 

Flax, seed at 0.45 	A crop group tolerance will not be appropriate at
this time until the Federal Register is issued revising the Crop Group
Regulation to establish the Oilseed Crop Group 20.  In the interim, HED
is recommending individual tolerances on all oilseeds to be listed in
the rapeseed subgroup.

Tolerances Proposed Under PP#6E7165

Avocado	0.7	0.6	Tolerance recommended, but additional field trial data
required as a condition of registration.

Tolerances Proposed Under PP#7E7245

Barley, grain	1.3	1.4	Adequate field trial data are available on barley
based on regional use.

Barley, straw	9.0	6.0

	Sapote, black	0.7	0.6	Tolerance recommendations are based on residue
data translated from avocado.

Canistel	0.7	0.6

	Sapote, mamey	0.7	0.6

	Mango	0.7	0.6

	Papaya	0.7	0.6

	Sapodilla	0.7	0.6

	Star Apple	0.7	0.6

	Additional Tolerances That Need to be Proposed Under PP#6E7105

Borage, Crambe, Cuphea, Echium, Flax seed, Gold of pleasure, Hare’s
ear mustard, Lesquerella, Lunaria, Meadowfoam, Milkweed, Mustard seed,
Oil radish, Poppy seed, Rapeseed, Sesame, Sweet rocket (rapeseed
subgroup);

Castor oil plant, Chinese tallowtree, Euphorbia, Evening primrose,
Jojoba, Niger seed, Rose hip, Safflower, Stokes aster

Sunflower, Tallowwood, Tea oil plant, Vernonia (sunflower subgroup);

Cotton (cotton subgroup)	

none	

0.45	

HED is recommending individual tolerances on all oilseeds to be listed
in the rapeseed subgroup.

5.2	Dietary Exposure and Risk TC \l2 "5.2  Dietary Exposure and Risk 

Reference:  Pyraclostrobin. Acute and Chronic Aggregate Dietary and
Drinking Water Exposure and Risk Assessments to Support New Use on Oat
Grain, Barley Grain, Oilseed (Crop Group 20), Fresh Herbs (Herbs
Subgroup 19A), Avocado, Black Sapote, Canistel, Mamey Sapote, Mango,
Papaya, Sapodilla, and Star Apple. PC Code: 099100; Decision Number:
370224; DP Number: 348308; S. Piper; 02/11/08.

Dietary risk assessment incorporates both exposure and toxicity of a
given pesticide.  The risk is expressed as a percentage of a maximum
acceptable dose (i.e., the dose which HED has concluded will result in
no unreasonable adverse health effects).  This dose is referred to as
the population adjusted dose (PAD).  HED is concerned when estimated
dietary risk exceeds 100% of the PAD.  

DEEM-FCID™ Program and Consumption Information

Pyraclostrobin acute and chronic dietary exposure assessments were
conducted using the Dietary Exposure Evaluation Model software with the
Food Commodity Intake Database (DEEM-FCID™, Version 2.03), which
incorporates consumption data from USDA’s Continuing Surveys of Food
Intakes by Individuals (CSFII), 1994-1996 and 1998.  The 1994-96, 98
data are based on the reported consumption of more than 20,000
individuals over two non-consecutive survey days.  Foods “as
consumed” (e.g., apple pie) are linked to EPA-defined food commodities
(e.g. apples, peeled fruit - cooked; fresh or N/S; baked; or wheat flour
- cooked; fresh or N/S, baked) using publicly available recipe
translation files developed jointly by USDA/ARS and EPA.  For chronic
exposure assessment, consumption data are averaged for the entire U.S.
population and within population subgroups, but for acute exposure
assessment are retained as individual consumption events.  Based on
analysis of the 1994-96, 98 CSFII consumption data, which took into
account dietary patterns and survey respondents, HED concluded that it
is most appropriate to report risk for the following population
subgroups: the general U.S. population, all infants (<1 year old),
children 1-2, children 3-5, children 6-12, youth 13-19, adults 20-49,
females 13-49, and adults 50+ years old.

For chronic dietary exposure assessment, an estimate of the residue
level in each food or food-form (e.g., orange or orange juice) on the
food commodity residue list is multiplied by the average daily
consumption estimate for that food/food form to produce a residue intake
estimate.  The resulting residue intake estimate for each food/food form
is summed with the residue intake estimates for all other food/food
forms on the commodity residue list to arrive at the total average
estimated exposure.  Exposure is expressed in mg/kg body weight/day and
as a percent of the cPAD.  This procedure is performed for each
population subgroup.

For acute exposure assessments, individual one-day food consumption data
are used on an individual-by-individual basis.  The reported consumption
amounts of each food item can be multiplied by a residue point estimate
and summed to obtain a total daily pesticide exposure for a
deterministic exposure assessment, or “matched” in multiple random
pairings with residue values and then summed in a probabilistic
assessment.  The resulting distribution of exposures is expressed as a
percentage of the aPAD on both a user (i.e., only those who reported
eating relevant commodities/food forms) and a per-capita (i.e., those
who reported eating the relevant commodities as well as those who did
not) basis.  In accordance with HED policy, per capita exposure and risk
are reported for all tiers of analysis.  However, for tiers 1 and 2, any
significant differences in user vs. per capita exposure and risk are
specifically identified and noted in the risk assessment.

Drinking Water Inputs

The drinking water residues used in the dietary risk assessment were
provided by EFED in the following memorandum: “Tier II Drinking Water
Assessment for the use of Pyraclostrobin (P.C. Code: 099100) on Oats and
Oilseed (canola and flax) (Headline Fungcide); Corn, Soybean, and Sugar
beets (Headline Fungcide); Fresh Herbs (crop group 19) and Tropical
Fruits (avocado, black sapote, canistel, mamey sapote, mango, papaya,
sapodilla, and star apple) (Pristine Fungicide); and Turf and
Ornamentals (Insignia Fungicide) (DP Barcodes 336190, 340588, 342584).
G. Rothman, 9/6/07” and incorporated directly into this dietary
assessment.  EFED selected the proposed aerial application on turf and
ornamentals as the use site to base their drinking water assessment
upon, since it provided the highest seasonal use rate (proposed or
registered) of pyraclostrobin (0.5 lbs a.i./acre with 6 maximum seasonal
applications at 14 day intervals).  Additionally, EFED believes that the
aerial use of pyraclostrobin on turf and ornamentals will pose the
upper-bound concentrations in surface and ground water since spray drift
increases and application efficiency decreases in an aerial application
technique.

The drinking water assessment provides Tier II (PRZM 3.12/EXAMS 2.98)
surface water modeling and Tier I (SCI-GROW, version 2.3) groundwater
modeling.  The modeling was conducted for the parent compound only.  The
residue concentrations from Tier II surface water modeling are not
expected to exceed 35.6 µg/L for the peak concentration, 2.3 µg/L for
the annual average concentration, and 1.5 µg/L for the 30 year average
concentration.  Residue concentration from Tier I groundwater modeling
is not expected to exceed 0.02 µg/L.  For acute exposures the 35.6
µg/L peak concentration was used.  For chronic exposures the 2.3 µg/L
annual average concentration was used.  These drinking water residues
were incorporated in the DEEM-FCID into the food categories “water,
direct, all sources” and “water, indirect, all sources.”

Residue Data Used for Acute and Chronic Assessments

For the acute dietary analysis, tolerance level or highest field trial
residues were used for all crops.  The crops for which the highest field
trial residues were used are as follows: Amaranth, leafy; Arugula;
Chrysanthemum; Cress, garden; Cress, upland; Dandelion, leaves; Fennel;
Parsley, leaves; Radicchio; Rhubarb; Spinach; Swiss chard; Beans, dry;
Celery; Lettuce, head; Lettuce, leaf; and Pea, dry.  One hundred percent
crop treated was assumed for all commodities in the assessment. For the
chronic dietary analysis, anticipated residues were derived for certain
crops (apple, broccoli, celery, collard, grape, lettuce, citrus, pepper,
mustard green and tomato), which are the major dietary contributors
based on preliminary runs. Experimentally derived processing factors for
apple juice, grape juice, citrus juices, tomato paste, tomato puree,
wheat flour, and wheat germ were applied. 

Results of Acute Dietary Exposure Analysis

The results of the aggregate acute dietary analysis for food and water
indicate that acute dietary risks do not exceed Agency’s level of
concern (< 100% of the aPAD) for the U.S. population and all subgroups.
At the 95th percentile, the U.S. population has an exposure from food
and drinking water that results in a risk estimate for the general U.S.
population at 1% of the aPAD.  The most highly exposed subpopulation is
“females 13-49 years” at 80% of the aPAD.  The results of the acute
dietary exposure analysis at the 95th percentile of exposure are
reported in Table 15 below.

Results of Chronic Dietary Exposure Analysis

The results of the aggregate chronic dietary analysis for food and
drinking water indicate that chronic dietary risks (food and drinking
water) do not exceed HED’s level of concern (<100% cPAD) for the U.S.
population and all subgroups.  The U.S. population exposure from food
and water results in a risk estimated at 19% of the cPAD.  The most
highly exposed population subgroup is “children 1 -2” with an
exposure estimated at 48% of the cPAD.  The results of the chronic
dietary exposure analysis are reported in Table 15, below.

Table 15.  Summary of Dietary Exposure and Risk for Pyraclostrobin –
Food & Water

Population Subgroup	Acute Dietary

(95th Percentile)	Chronic Dietary	Cancer

	Dietary Exposure (mg/kg/day)	% aPAD	Dietary Exposure

(mg/kg/day)	% cPAD	Dietary Exposure

(mg/kg/day)	Risk

General U.S. Population	0.043	1.4	0.0061	19	A separate quantitative
cancer risk assessment is not required.  

All Infants (< 1 year old)	0.055	1.8	0.011	33

	Children 1-2 years old	0.072	2.4	0.016	48

	Children 3-5 years old	0.064	2.2	0.012	36

	Children 6-12 years old	0.046	1.5	0.0074	22

	Youth 13-19 years old	0.035	1.2	0.0043	13

	Adults 20-49 years old	0.039	1.3	0.0050	15

	Adults 50+ years old	0.041	1.4	0.0057	17

	Females 13-49 years old	0.040	80	0.0047	14

	

Conclusions

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.  Since risk estimates are below HED’s level of concern, a
more highly refined analysis is not needed at this time.  Of note is
that contribution from drinking water is minimal.  HED concludes that
the acute and chronic exposure estimates are unlikely to underestimate
actual acute or chronic exposure.

5.3	Anticipated Residue and Percent Crop Treated (%CT) Information TC
\l2 "5.3 Anticipated Residue and Percent Crop Treated (%CT) Information 

The acute analysis was conducted using tolerance level residues or the
highest residues for all commodities. These tolerance level or highest
residues were 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 and chronic analyses. 

The chronic dietary assessment was conducted using tolerance level
residues for all crops except for apple, celery, grape, head lettuce,
leaf lettuce, orange, pepper, spinach, tomato and additional crops in
the leafy vegetables group where anticipated 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.

6.0	Residential (Non-Occupational) Exposure/Risk Characterization  TC
\l1 "6.0	Residential (Non-Occupational) Exposure/Risk Characterization 

A product containing pyraclostrobin (i.e., Insignia®) is registered for
application to residential turf grass and recreational sites.  It may be
applied to turf at rates ranging from 0.28 to 0.5 lb ai/A, at intervals
of 14 to 28 days; and the maximum seasonal application rate is 3 lb
ai/A.  The residential exposure assessment was prepared in an HED
memorandum dated 8/19/04 (D298017, K. O’Rourke).  Residential and
recreational turf applications are applied by professional pest control
operators (PCOs) only, and therefore, residential handler exposures do
not occur.  There is, however, a potential for exposure to homeowners in
residential settings from entering previously treated lawns where
children might play and adults might work or play.  As a result, risk
assessments have been completed for postapplication scenarios.  The
short-term MOEs for each postapplication scenario resulted in MOEs above
100, and therefore are not of concern.  For toddlers, the short-term
dermal MOE is 180 (0.027 mg/kg/day) and the combined incidental oral MOE
is 620 (0.009425 mg/kg/day; hand-to-mouth activities), and combined
dermal and oral exposures result in and MOE of 140.  Dermal and
incidental oral exposures are combined because they share common toxic
effects; i.e., decreased body weight gain and decreased food
intake/efficiency.  For adults, the short-term dermal MOE is 260 (0.019
mg/kg/day).  

Recreational exposures to turf are expected to be similar to, or in many
cases less than, those evaluated for residential postapplication
exposure and risk; and therefore, a separate recreational exposure
assessment was not conducted.

Spray drift is always a potential source of exposure to residents nearby
to spraying operations.  This is particularly the case with aerial
application, but, to a lesser extent, could also be a potential source
of exposure from the ground application method employed for
pyraclostrobin.  The Agency has been working with the Spray Drift Task
Force, EPA Regional Offices and State Lead Agencies for pesticide
regulation and other parties to develop the best spray drift management
practices.  The Agency is now requiring interim mitigation measures for
aerial applications that must be placed on product labels/labeling.  The
Agency has completed its evaluation of the new data base submitted by
the Spray Drift Task Force, a membership of U.S. pesticide registrants,
and is developing a policy on how to appropriately apply the data and
the AgDRIFT computer model to its risk assessments for pesticides
applied by air, orchard airblast and ground hydraulic methods.  After
the policy is in place, the Agency may impose further refinements in
spray drift management practices to reduce off-target drift and risks
associated with aerial as well as other application types where
appropriate.

7.0	Aggregate Risk Assessments and Risk Characterization  TC \l1 "7.0
Aggregate Risk Assessments and Risk Characterization 

In accordance with the FQPA, HED must consider and aggregate (add)
pesticide exposures and risks from three major sources: food, drinking
water, and residential exposures.  In an aggregate assessment, exposures
from relevant sources are added together and compared to quantitative
estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can
be aggregated.  When aggregating exposures from various sources, HED
considers both the route and duration of exposure.  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.

Based on the proposed Section 3 food crop uses, aggregate assessments
were conducted for acute and chronic dietary exposures (food + drinking
water), and existing short-/intermediate-term residential exposures
(i.e., chronic dietary, plus incidental oral and dermal exposures for
kids, and chronic dietary, plus dermal exposures for adults).  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.  

To assess aggregate acute and chronic dietary risks, estimates of
pesticide residues in drinking water (EDWCs) were incorporated directly
into the dietary exposure analysis.  Refer to section 5.2 for these risk
estimates.  

The short-/intermediate-term aggregate risk assessment takes into
account average exposure estimates from dietary consumption of
pyraclostrobin (food and drinking water) and
non-occupational/residential uses (turf).  Postapplication exposures
from the use on turf are considered predominantly short-term (1-30
days).  To calculate the short-/intermediate-term aggregate risk
estimates, the chronic dietary exposure (food + drinking water) is added
to the residential exposures using the inverse MOE methodology described
below (see Table 16 below).  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 200, 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.

Table 16.  Short-/Intermediate Term Aggregate Risk Calculations 

Population	

Dermal Exposure	

Oral Exposure	

Total Combined MOE2

	

NOAEL

mg/kg/day	

Exposure

mg/kg/day	

MOE1	

NOAEL mg/kg/day	

Incidental Oral Exposure mg/kg/day 	Chronic Dietary (Food + Water)
mg/kg/day	

MOE1

	

Children 1-2 yrs	

5	

0.027	

180	

5.8	

0.009425	

0.0164	

220	

100

Adults	

5	

0.019	

260	

5	

NA	

0.00613	

820	

200

1 The Level of Concern MOE is 100.

2 Total Combined MOE = 1/ [(1/MOEDermal) + (1/MOEOral)]

8.0	Cumulative Risk Characterization/Assessment  TC \l1 "8.0	Cumulative
Risk Characterization/Assessment 

Unlike other pesticides for which EPA has followed a cumulative risk
approach based on a common mechanism of toxicity, EPA has not made a
common mechanism of toxicity finding as to pyraclostrobin and any other
substances and pyraclostrobin does not appear to produce a toxic
metabolite produced by other substances. For the purposes of this
tolerance action, therefore, EPA has not assumed that pyraclostrobin has
a common mechanism of toxicity with other substances. For information
regarding EPA’s efforts to determine which chemicals have a common
mechanism of toxicity and to evaluate the cumulative effects of such
chemicals, see the policy statements released by EPA’s Office of
Pesticide Programs concerning common mechanism determinations and
procedures for cumulating effects from substances found to have a common
mechanism on EPA’s website at   HYPERLINK
"http://www.epa.gov/pesticides/cumulative/" 
http://www.epa.gov/pesticides/cumulative/ .

9.0	Occupational Exposure/Risk Pathway  TC \l1 "9.0	Occupational
Exposure/Risk Pathway 

Reference: Pyraclostrobin: Occupational and Residential Risk Assessment
to Support Request for Section 3 Registrations on Oats and Oilseed Crop
group (Foliar and Seed Treatment), Herbs, and Tropical Fruits. (DP#:
348792; PC#: 099100) K. O’Rourke; 01/31/08.

9.1	Short-/Intermediate-Term Handler Risk  TC \l2 "9.1
Short-/Intermediate-Term Handler Risk 

Foliar and In-Furrow Treatment

Occupational handlers may experience short-/intermediate-term exposure
to pyraclostrobin while mixing/loading and applying sprays to
agricultural crops.  No chemical-specific handler exposure data were
submitted in support of this use pattern.  It is the policy of the HED
to use data from the Pesticide Handlers Exposure Database (PHED) Version
1.1 as presented in PHED Surrogate Exposure Guide (8/98) to assess
handler exposures when chemical-specific monitoring data are not
available ( HED Science Advisory Council for Exposure Draft Policy # 7,
dated 1/28/99).  

The results of the occupational handler exposure and risk assessment
indicate that risks are not of concern with baseline clothing, or in
some cases, when gloves and respirator are used to mitigate exposure. 
[Note: The respirator unit exposure value represents a PF 5
NIOSH-approved filtering face-piece respirator (e.g., dust mask), which
is considered to provide an 80% reduction in inhalation exposure.] 
Exposure assumptions and MOE estimates are summarized in Table 17. 

It is feasible for the same individual to mix/load and apply
formulations, especially for groundboom and airblast applications,
however, appropriate data are not available in PHED for which unit
exposures for these combined activities can be derived.  HED does not
recommend simply adding the unit exposure values for each job function
because any extrapolation error (i.e., exposure from the amount ai
handled in the study to that of a real-life application) would be
magnified, leading to greater uncertainty.  For information and
characterization purposes, even with the over-estimation uncertainty,
the MOEs for these combined activities for groundboom and airblast
application of pyraclostrobin would be above the LOC of 100, and not of
concern (i.e., dermal/inhalation MOEs of 1,400/210 and 1,200/510,
respectively).

The proposed Headline® Fungicide label requires chemical resistant
gloves, however, a respirator is not indicated.  In addition, the
minimum level of PPE for handlers is based on acute toxicity for the
end-use products.  The Registration Division (RD) is responsible for
ensuring that PPE listed on the label is in compliance with the Worker
Protection Standard (WPS).



	Table 17.  Summary of  MOEs for Occupational Handlers of Pyraclostrobin
(Foliar Treatment)

Exposure Scenario (Scenario #)	Dermal Unit Exposure (mg/lb ai) 1
Inhalation

Unit

Exposure

(mg/lb ai) 1	Use Site	Application 

Rate 

(lb ai/A) 2	Area Treated

(A/day) 3	Daily Dose

(mg/kg/day) 4	Short-/Int-term 

MOE 5

Dermal	Inhalation	Dermal	Inhalation

Mixer/Loader

(1) Mixing/Loading Liquid for Aerial application or Chemigation	2.9

or

0.023

(w/gloves)	0.0012

or

0.00024

(w/

respirator)

	Oats	0.15	1,200	1.2

0.0097

(gloves)	0.0031

0.00062

(respirator)	4.1

520

(gloves)	75

370

(respirator)

	Canola & Flax	0.10	350	0.24

0.0019

(gloves)	0.00060	21

2,700

(gloves)	380

(2) Mixing/Loading Liquid for Groundboom application or Chemigation

	In-Furrow tmt	0.20	200	0.27

0.0021

(gloves)	0.00069	18

2,300

(gloves)	340

	Oats	0.15	200	0.20

0.0016

(gloves)	0.00051	25

3,100

(gloves)	450

	Canola & Flax	0.10	80	0.054

0.00043

(gloves)	0.00014	92

12,000

(gloves)	1,700

(3) Mixing/Loading Dry Flowables for Aerial application or Chemigation
0.066	0.00077	Turf & Ornamentals	0.50	350	0.027	0.0019	190	120

	Herbs & Tropical Fruit	0.15	350	0.0081	0.00058	620	400

(4) Mixing/Loading Dry Flowables for Groundboom application

	Herbs	0.15	80	0.0018	0.00013	2,700	1,700

(5) Mixing/Loading Dry Flowables for Airblast application

	Tropical Fruit	0.15	40	0.00092	0.000066	5,400	3,500

Applicator

(6) Applying Sprays with Fixed-wing Aircraft	0.005	0.000068	Turf &
Ornamentals	0.50	350	0.0020	0.00017	2,400	1,400

	Oats	0.15	1,200	0.0021	0.00017	2,400	1,300

	Herbs & Tropical Fruit	0.15	350	0.00061	0.000051	8,200	4,500

	Canola & Flax	0.10	350	0.00041	0.000034	12,000	6,800

(7) Applying Sprays with Open Cab Groundboom 	0.014	0.00074	In-Furrow
tmt	0.20	200	0.0013	0.00042	3,800	540

	Oats	0.15	200	0.00098	0.00032	5,100	730

	Herbs	0.15	80	0.00039	0.00013	13,000	1,800

	Canola & Flax	0.10	80	0.00026	0.000085	19,000	2,700

(8) Applying Sprays with Open Cab Airblast Sprayer	0.36	0.0045	Tropical
Fruit	0.15	40	0.0050	0.00039	990	600

Flagger

(9) Flagging to Support Aerial Applications	0.011	0.00035	Turf &
Ornamentals	0.50	350	0.0045	0.00088	1,100	260

	Oats, Herbs & Tropical Fruit	0.15	350	0.0013	0.00026	3,700	880

	Canola & Flax	0.10	350	0.00090	0.00018	5,600	1,300

1 Dermal unit exposure values represent long pants, long sleeved shirts,
shoes, and socks; values representing the addition of chemical-resistant
gloves are shown for those scenarios in which the MOEs do not reach 100
at baseline.  Inhalation unit exposure values represent no respirator,
except for “Oats” in Scenario #1, for which a dust-mist respirator
was added.  Values are reported in the PHED Surrogate Exposure Guide
dated August 1998. 

2 Application rates are based on maximum values found in proposed labels
(See Table 1)

3 Daily area treated is based on the area that can be reasonably applied
in a single day for each exposure scenario, based on the application
method and formulation/packaging type. (standard EPA/OPP/HED values).

4 Daily Dose (mg/kg/day) = (Unit Exposure * % Absorption * Application
rate * Area treated) / Body Weight of 60-kg for dermal or 70-kg for
inhalation; where dermal absorption is 14%..

5 Short-/Intermediate-Term MOE = NOAEL / Daily Dose.  The dermal NOAEL
is 5 mg/kg/day, and the inhalation NOAEL is 0.23 mg/kg/day.  The LOC is
100.



Seed Treatment

Occupational handlers may experience short-/intermediate-term exposure
to pyraclostrobin while performing seed treatment activities, including
several distinct handling activities, each with its own exposure
potential.  These activities are: (1) loader/applicator; (2) sewer; (3)
bagger; (4) multiple activities (including cleaning and forklift
operation); and, (5) seed planters.  

No chemical-specific handler exposure data were submitted in support of
this use pattern.  For assessing seed treatment activities, unit
exposure data were taken from HED Science Advisory Council for Exposure
Policy 14: Standard Operating Procedures for Seed Treatment.  The amount
of ai handled depends on the application rate (lb ai/100 lb seed) and
the pounds of seed treated in a day (or the pounds of seed that can be
planted in a day), all of which may vary, depending upon the seed type. 
Values for the amount of seed treated and planted per day were obtained
from HED’s Standard Operating Procedure (SOP) #15.  Exposure and risk
estimates for seed treatment handlers were calculated based on canola
data (commercial rate assumed to be 718,000 lb seed/day) for seed
treatment, and flax data for seed planting, which represent the maximum
combination of application rate and amount handled for the proposed
crops.  The results are presented in Table 18.

For the proposed seed treatment uses, all seed treatment activities
result in MOEs greater than the LOC of 100 with baseline clothing, or
baseline plus gloves and respirator, and therefore, are not of concern. 
While there is a data gap for on-farm seed treatment (i.e., the data
available for on-farm seed treatment represents a dust formulation in a
planter box, which is not applicable) this scenario is not likely to
result in risks of concern because seed treatment activities in the
commercial setting (estimated in Table 18), which handle much greater
quantities of seed, are not of concern.  [Note: The respirator unit
exposure value represents a PF 5 NIOSH-approved filtering face-piece
respirator (e.g., dust mask), which is considered to provide an 80%
reduction in inhalation exposure.]

The proposed BAS 500 ST label is a supplemental label only, and does not
provide information regarding personal protective equipment (PPE) (i.e.,
whether gloves and a respirator are currently required).  In addition,
the minimum level of PPE for handlers is based on acute toxicity for the
end-use product.  The Registration Division (RD) is responsible for
ensuring that PPE listed on the label is in compliance with the Worker
Protection Standard (WPS).

Table 18.  Summary of  MOEs for Seed Treatment Activities

Activity	Dermal Unit Exposure (mg/lb ai) 1	Inhalation

Unit

Exposure

(mg/lb ai) 1	Application 

Rate 

(lb ai/

lb seed) 2	Seed Handled per Day

(lb seed) 3	Daily Dose

(mg/kg/day) 4	Short-/Int-term 

MOE 5

	Dermal	Inhalation	Dermal	Inhalation

Loader/ Applicator	0.023

(w/gloves)	0.00034	0.0004	718,000	0.015	0.0014	320	160

Sewer	0.0062	0.00023

	0.0042	0.00094	1,200	240

Bagger	0.0091	0.00016

	0.0061	0.00066	820	350

Multiple

Activity	0.042

(w/gloves)	0.0016

or

0.00032

(w/respirator)

	0.028	0.0066

or

0.0013

(w/respirator)	180	35

or

180

(w/respirator)

On-Farm	No data	No data

6,700	--	--	--	--

Seed Planter	0.25

(w/gloves)	0.0034

	0.0016	0.00013	3,200	1,800

1 Dermal unit exposure values represent baseline clothing (long pants,
long sleeved shirts, shoes, and socks), except where gloves are
indicated (for planting, gloves are for loading only).  Inhalation unit
exposure values represent no respirator, except for “multiple
activity” scenario.  There is a data gap for on-farm seed treatment;
the formulation is a water-dispersible granule for which the label
indicates standard slurry or mist-type seed treatment equipment should
be used.  The data available for on-farm seed treatment represents a
dust formulation in a planter box scenario, which is not applicable.

2 Application rates are based on maximum values in proposed seed
treatment label (See Table 1)

3   SEQ CHAPTER \h \r 1 Values for amount of seed handled for all
activities are based on an assumed rate for canola, except the on-farm
and planter scenarios, which were based on flax.

4 Daily Dose (mg/kg/day) = (Unit Exposure * % Absorption * Application
rate * Seed Handled) / Body Weight of 60-kg for dermal or 70-kg for
inhalation; where dermal absorption is 14%.

5 Short-/Intermediate-Term MOE = NOAEL / Daily Dose.  The dermal NOAEL
is 5 mg/kg/day, and the inhalation NOAEL is 0.23 mg/kg/day.  The LOC is
100.

9.2	Short-/Intermediate-Term Postapplication Risk  TC \l2 "9.2
Short-/Intermediate-Term Postapplication Risk 

This Section 3 action for pyraclostrobin involves foliar applications to
agricultural crops.  Therefore, 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 (MRID#s: 45118727,
45118724, 45118726, and 45118728 and 45118729).  An overview of each
study was provided in a previous assessment (D269670, K. O’Rourke,
9/30/2002); a summary of the results is provided in Table 19. 

The DFR data were used to estimate restricted entry intervals (REIs) by
extrapolating, where possible, to the proposed crops.  It was found that
the type of formulation used influences the DFR profile; therefore, DFR
data for both the emulsifiable concentrate and water-dispersible granule
formulations were considered.  Average percent initial DFR values were
calculated (i.e., 18% for emulsifiable concentrate and 20% for
water-dispersible granule) and used to estimate surrogate residue values
for each crop, according to its proposed formulation.  Although
uncertainties are introduced into the assessment when crop-specific
residues are used to estimate residues for other types of crops, it is
believed to be more realistic than using default assumptions

In addition to these residue data, transfer coefficients (Tc) are used
to relate the foliage residues to activity patterns (e.g., scouting) to
estimate potential human exposure.  The transfer coefficients used in
this assessment are from an interim transfer coefficient policy
developed by HED’s Science Advisory Council for Exposure using
proprietary data from the Agricultural Re-entry Task Force (ARTF)
database (policy # 3.1).

The estimated short-/intermediate-term MOEs are presented in Table 20. 
The results of the postapplication exposure and risk assessment indicate
that MOEs of 100 are achieved on Day 0 for all 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.  The proposed labels indicate an REI
of 12 hrs, which is in compliance with the WPS.

Table 19.  Summary of DFR Study Results

Crop	

Location

(state)	

Formu-lation	

Application Rate

(lb ai/A)	

Number 

of Apps.	

Interval	

r2	

Initial DFR

(% of 

Appl. Rate)	

Dissipation

(% per day)	

Half-life (days)

peaches	

CA	

WDG	

0.12	

5	

7 days	

0.84	

22	

2	

27.8

peaches	

GA	

WDG	

0.12	

5	

7 days	

0.97	

15	

11	

6

peaches	

PA	

WDG	

0.12	

5	

7 days	

0.94	

22	

9	

7.7

Peaches Average	

	

	

	

	

	

20	

7	

strawberries	

NC	

WDG	

0.18	

5	

7 days	

0.77	

26	

15	

4.2

strawberries	

CA	

WDG	

0.18	

5	

7 days	

0.98	

25	

15	

4.4

strawberries	

OR	

WDG	

0.18	

5	

7 days	

0.91	

12	

13	

4.9

      Strawberry Average	

	

	

	

	

	

21	

14	

peanuts	

NC	

EC	

0.25	

5	

14 days	

0.91	

18	

26	

2.3

peanuts	

GA	

EC	

0.25	

5	

14 days	

0.77	

17	

61*	

0.74

peanuts	

TX	

EC	

0.25	

5	

14 days	

0.91	

18	

24	

2.5

  Peanuts Average	

	

	

	

	

	

18	

25*	

grapes	

CA	

WDG	

0.18	

3	

14 days	

0.97	

22	

6	

11.1

grapes	

WA	

WDG	

0.18	

3	

14 days	

0.94	

25	

6	

11.8

grapes	

PA	

WDG	

0.18	

3	

14 days	

0.82	

14	

4	

15.6

      Grapes WDG Average	

	

	

	

	

	

20	

5	

grapes	

CA	

EC	

0.18	

3	

14 days	

0.95	

14	

9	

7.4

grapes	

WA	

EC	

0.18	

3	

14 days	

0.9	

22	

9	

7.5

grapes	

PA	

EC	

0.18	

3	

14 days	

0.79	

12	

5	

13.9

grapes	

CA	

EC	

0.15	

6	

10 days	

0.9	

6	

6	

12

grapes	

NY	

EC	

0.15	

6	

10 days	

0.92	

28	

6	

11.2

grapes	

WA	

EC	

0.15	

6	

10 days	

0.9	

24	

4	

17.3

      Grapes EC Average	

	

	

	

	

	

18	

7	

EC Average	

	

	

	

	

	

18	

13	

    WDG Average	

	

	

	

	

	

20	

9	

WDG = water dispersible granule

EC = emulsifiable concentrate

* The results from the Georgia site reflect uncharacteristically high
rainfall during the monitoring period.  This is not representative of
typical conditions, therefore, the dissipation from this site was not
included in the average.

Table 20.  Summary of Estimated Postapplication MOEs for Foliar
Treatments

Crop	Application Rate

(lb ai/A) 1	DAT 2	DFR 3

(μg/cm2)	TC 4

(cm2/hr)	Activity 4	Short-/Int-

Term MOE 5

Canola & Flax 	0.10	0	0.20	100	Irrigating and scouting immature/low
foliage plants	13,000

1,500	Irrigating and scouting mature/high foliage plants	890

Oats	0.15	0	0.30	100	Irrigating and scouting immature/low foliage plants
8,900

1,500	Irrigating and scouting mature/high foliage plants	590

Herbs

0	0.34	500	Irrigation, scouting, thinning, weeding immature plants	1,600

1,500	Irrigating and scouting mature plants	530

2,500	Hand harvesting, pruning, and thinning mature plants	320

Tropical Fruit

0	0.34	100	Propping	8,000

1,000	Irrigation, scouting, weeding	800

1,500	Harvesting, pruning, training, tying	530

3,000	Thinning	270

1 Maximum application rate indicated on proposed labels (see Table 1). 

2 DAT = Days after treatment needed to reach the LOC of 100; DAT 0 = the
day of treatment, after sprays have dried; assumed to be approximately
12 hours.  

3 DFR (µg/cm2) = Application rate (lb ai/A) x CF (4.54E+8 ug/lb) x CF
(2.47E-8 A/cm2) x Initial Fraction of ai Retained on the Foliage (from
Table 19, used EC average [18%] for canola, flax and oats, and WDG
average [20%] for herbs and tropical fruits).

4 TC (cm2/hr) = transfer coefficients and associated activities from
ExpoSAC Policy Memo #003.1 “Agricultural Transfer Coefficients”,
8/17/2000.

5 MOE = MOE on the corresponding DAT.  MOE = NOAEL / Daily Dose.  

   Daily Dose = [(DFR x  TC x 14% Dermal absorption  x  8-hr Exposure
Time)] / [(CF: 1000 µg/mg) x (60-kg Body Weight)]

   Short-/intermediate-term Dermal NOAEL = 5 mg/kg/day.  The LOC is 100.

10.0	Data Needs and Label Recommendations  TC \l1 "10.0	Data Needs and
Label Recommendations 

10.1	Residue Chemistry Data Needs and Label Recommendations  TC \l2
"10.1	Residue Chemistry Data Needs and Label Recommendations 

For Petition #6F7105

860.1500 Crop Field Trials

Oats:  No residue data are submitted for oat forage.  The petitioner did
not provide residue data or propose a tolerance for oat forage because
applications are made after the growth stages at which oat is foraged. 
Based on the current proposed use patterns, the Agency will not require
residue data or a tolerance for oat forage.

860.1900 Field Accumulation in Rotational Crops

Label revisions are required to specify a 14-day plantback interval
restriction for all annual crops that are not registered.

860.1550 Proposed Tolerances

The petitioner should submit a revised Section F reflecting the
recommended tolerances and commodity definitions presented in Table 14.

The petitioner should submit a revised Section F to propose individual
tolerances of 0.45 ppm for all oilseeds in subgroups rapeseed,
sunflower, and cotton, as follows: 1) rapeseed (i.e., borage, crambe,
cuphea, echium, flax seed, gold of pleasure, hare’s ear mustard,
lesquerella, lunaria, meadowfoam, milkweed, mustard seed, oil radish,
poppy seed, rapeseed, sesame, and sweet rocket); 2) sunflower (i.e., 
Castor oil plant, Chinese tallowtree, Euphorbia, Evening primrose,
Jojoba, Niger seed, Rose hip, Safflower, Stokes aster, Sunflower,
Tallowwood, Tea oil plant, Vernonia ); and 3) cotton (only entry
presently in this subgroup).

Note: The existing tolerances on sunflower at 0.3 ppm and cotton,
undelinted seed at 0.3 ppm should be removed from 40 CFR §180.582.

860.1520 Processed Food and Feed

Oats:  No residue data for the oat processed commodities (flour and
groats/rolled oats) are submitted.  However, data from the wheat
processing studies (MRID #’s 45118620 and 45321101) can be translated
to adequately support the proposed use on oat.  Based on the wheat
studies, residues are not expected to concentrate in oat processed
commodities. 

Barley:  No residue data for the barley processed commodities (bran and
pearled) are submitted.  However, data from the wheat processing studies
(MRID #’s 45118620 and 45321101) can be translated to adequately
support the proposed use on barley.  Based on the wheat studies,
residues are not expected to concentrate in barley processed
commodities.

For Petition #6E7165

860.1500 Crop Field Trials

The submitted residue data for avocado are inadequate to fulfill data
requirements because the field trials were conducted at exaggerated
rates (ca 2.6x).  Since the submitted data represent an overestimate of
the residues expected from the proposed use, HED considers that the
tolerance for avocado may need to be reduced.  Also, since the proposed
use is for late season foliar application, includes a 0-day preharvest
interval, and these data are being translated to support a wide number
of tropical/subtropical fruits, HED requests that the petitioner provide
additional, bridging field trial data (i.e., two to three field trials
at the proposed label rate of 2 applications, total 0.3 lb ai/season) as
a condition of registration.

860.1900 Field Accumulation in Rotational Crops

Label revisions are required to specify a 14-day plantback interval
restriction for all annual crops that are not registered.

860.1550 Proposed Tolerances

The petitioner should submit a revised Section F to correct the
tolerance residue definition (parent + metabolite) and to make it
consistent with the definition listed in 40 CFR §180.582 (a)(1).  The
revised Section F should also incorporate the recommended tolerances and
commodity definitions presented in Table 14.

For Petition #7E7245

860.1500 Crop Field Trials

Barley:  No residue data were submitted for barley forage, and these
data are normally required to support the amended use pattern.  
However, the petitioner did not provide residue data or propose a
tolerance for barley hay because applications are made after the growth
stages at which barley hay is harvested.  Based on the current proposed
use patterns, the Agency will not require residue data or a tolerance
for barley hay.   

860.1520 Processed Food and Feed

Barley:  Residue data for the barley processed commodities (pearled
barley and bran) are normally required.  However, data from the wheat
processing studies (MRID #’s 45118620 and 45321101) can be translated
to adequately support the proposed use on barley.  Based on the wheat
studies, residues are not expected to concentrate in barley processed
commodities.

860.1900 Field Accumulation in Rotational Crops

Label revisions are required to specify a 14-day plantback interval
restriction for all annual crops that are not registered.

860.1550 Proposed Tolerances

The petitioner should submit a revised Section F reflecting the
recommended tolerances and commodity definitions presented in Table 14.

10.2	Occupational Label Recommendations  TC \l2 "10.2	Occupational Label
Recommendations 

The proposed Headline® Fungicide label requires chemical resistant
gloves; however, a respirator is not indicated and is needed for the
handler scenario of mixing/loading liquids for aerial application or
chemigation.  

The proposed BAS 500 ST label is a supplemental label only, and does not
provide information regarding personal protective equipment (PPE).  Such
PPE information should be added to the label.  Gloves are needed for
several seed treatment scenarios, and a respirator is needed for the
multiple activity scenario.

11.0	International Residue Limit Status  TC \l1 "11.0	International
Residue Limit Status 

The Codex Alimentarius Commission, Mexico and Canada have not
established any maximum residue limits (MRLs) for residues of
pyraclostrobin in or on raw agricultural commodities, although a variety
of MRLs are pending in Canada.  Therefore, there are no questions of
compatibility of U.S. tolerances with International MRLs at the present
time.



INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name:  methyl
[2-[[[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxy]methyl]phenyl]methoxy
carbamate	Common Name:

Pyraclostrobin	(   Proposed tolerances

(  Reevaluated tolerance

(  Other	Date: 12/20/07

Codex Status (Maximum Residue Limits)	U. S. Tolerances

No Codex proposal step 6 or above

No Codex proposal step 6 or above for the crops requested 
Petition Numbers:  6E7105, 6E7165, and 7E7245

DP#s:  334535, 336189, and 343754

Other Identifier: 

Residue definition (step 8/CXL):  pyraclostrobin (fat soluble)
Reviewers/Branch: B. Cropp-Kohlligan, G. Otakie, J. Stokes / RRB4

	Residue definition in PP#6E7105, PP#6E7165,and PP#7E7245:  Combined
residues of pyraclostrobin and BF 500-3, expressed as pyraclostrobin.

Crop (s)	MRL (mg/kg)	Crop(s)	Recommended Tolerance (ppm)

Oats	0.5	PP#6E7105

Papaya	0.05	Oats grain	1.2

Barley	0.5	Oats, hay 	18

Oats, straw	15

Canola, seed	0.45 

Flax, seed 	0.45

Borage	0.45

Crambe	0.45

Cuphea	0.45

Echium	0.45

Flax seed	0.45

Gold of pleasure	0.45

Hare’s ear mustard	0.45

Lesquerella	0.45

Lunaria	0.45

Meadowfoam	0.45

Milkweed	0.45

Mustard seed	0.45

Oil radish	0.45

Poppy seed	0.45

Rapeseed	0.45

Sesame	0.45

Sweet rocket	0.45

Castor oil plant	0.45

Chinese tallowtree	0.45

Euphorbia	0.45

Evening primrose	0.45

Jojoba	0.45

Niger seed	0.45

Rose hip	0.45

Safflower	0.45

Stokes aster	0.45

Sunflower	0.45

Tallowwood	0.45

Tea oil plant	0.45

Vernonia	0.45

Cotton	0.45

PP#6E7165

Avocado	0.6

Sapote, black	0.6

Canistel	0.6

Sapote, mamey	0.6

Mango	0.6

Papaya	0.6

Sapodilla	0.6

Star Apple	0.6

PP#7E7245

Barley, grain	1.4

Barley, straw	6.0

Limits for Canada	Limits for Mexico

(No Limits

(No Limits for the crops requested	(No Limits

(No Limits for the crops requested

Residue definition:	Residue definition:

Crop(s)	MRL (mg/kg)	Crop(s)	MRL (ppm)

	Notes/Special Instructions:



12.0	Appendix: Toxicity Profile  TC \l1 "12.0	Appendix: Toxicity Profile

12.1	Appendix 1.: Pyraclostrobin Toxicology Requirements and Available
Studies for Food Uses  TC \l2 "12.1	Appendix 1.: Pyraclostrobin
Toxicology Requirements and Available Studies for Food Uses 

Appendix 1: Pyraclostrobin Toxicology Requirements and Available Studies
for Food Uses.

  SEQ CHAPTER \h \r 1 Test 

	Technical

	Required	Satisfied

870.1100	Acute Oral Toxicity	

870.1200	Acute Dermal Toxicity	

870.1300	Acute Inhalation Toxicity	

870.2400	Primary Eye Irritation	

870.2500	Primary Dermal Irritation	

870.2600	Dermal Sensitization		yes

yes

yes

yes

yes

yes	yes

yes

yes

yes

yes

yes

870.3100	Oral Subchronic (rodent)	

870.3150	Oral Subchronic (dog)	

870.3200	28-Day Dermal	

870.3465	28-Day Inhalation		yes

yes

yes

yes	yes

yes

yes

yes

870.3700a	Developmental Toxicity (rat)	

870.3700b	Developmental Toxicity (rabbit)	

870.3800	Reproduction		yes

yes

yes	yes

yes

yes

870.4100a	Chronic Toxicity (rat)	

870.4100b	Chronic Toxicity (dog)	

870.4200a	Oncogenicity (rat)	

870.4200b	Oncogenicity (mouse)		yes

yes

yes

yes	yes

yes

yes

yes

870.5100	Mutagenicity—Gene Mutation - bacterial	

870.5300	Mutagenicity—Gene Mutation - mammalian	

870.5375	Mutagenicity—Structural Chromosomal Aberrations	

870.5395	Mutagenicity—Microneucleus - mammalian

870.5550	Mutagenicity—Unscheduled DNA - mammalian 		yes

yes

yes

yes

yes	yes

yes

yes

yes

yes

870.6100a	Acute Delayed Neurotox. (hen)	

870.6100b	90-Day Neurotoxicity (hen)	

870.6200a	Acute Neurotox. Screening Battery (rat)	

870.6200b	90 Day Neuro. Screening Battery (rat)	

870.6300	Develop. Neuro		no

no 

yes

yes

no

	-

- 

yes

yes

-

870.7485	General Metabolism	

870.7600	Dermal Penetration		yes

yes	yes

yes



12.2	Appendix 2.: Acute Toxicity Data on Pyraclostrobin Technical  TC
\l2 "12.2	Appendix 2.: Acute Toxicity Data on Pyraclostrobin Technical 

  SEQ CHAPTER \h \r 1 Appendix 2. Acute Toxicity Profile:

  SEQ CHAPTER \h \r 1 Table 1. Acute Toxicity Data on Pyraclostrobin
Technical

Study/ Species	MRID	Results	Toxicity  Category

870.1100 Acute Oral, Rats	45118302	LD50 = > 5000 mg/kg	IV

870.1200 Acute Dermal, Rabbits	45118305	LD50 = >2000mg/kg	III

870.1300 Acute Inhalation, Rats	45118308	0.31 mg/L < LC50 < 1.07 mg/L	II

870.2400 Primary Eye Irritation, Rabbits	45118311	Moderate eye
irritation; MAS 4.6/110	III

870.2500 Primary Skin Irritation, Rabbits	45118314	Moderate skin
irritation; MAS 2.2/8.0	III

870.2600 Dermal Sensitization, Guinea pig	45118317	Not a skin sensitizer
N/A

12.3	Appendix 3.: Subchronic, Chronic and Other Toxicity Profile  TC
\l2 "12.3	Appendix 3.: Subchronic, Chronic and Other Toxicity Profile 

  SEQ CHAPTER \h \r 1 Appendix 3. Subchronic, Chronic and Other Toxicity
Profile

Guideline No./Study Type	MRID No. (year)/ Classification/Doses	Results

870.3100

90-Day oral toxicity (rat)	45118321 (1999)

Acceptable/guideline

0, 50, 150, 500, 1000, 1500 ppm 

M: 0, 3.5, 10.7, 34.7, 68.8, 105.8 mg/kg/day; 

F: 0, 4.2 12.6, 40.8, 79.7,118.9  mg/kg/day	NOAEL = 10.7 mg/kg/day

EL = 34.7 mg/kg/day based on ↓body weight/ weight gain in males,
↓food intake (both sexes), ↑ relative liver wt and spleen wt in
females and histopathology of duodenum and liver in males, and spleen in
both sexes.

870.3100

90-Day oral toxicity

(mouse)	45118320 (1999) 

Acceptable/guideline

0, 50, 150, 500, 1000, 1500 ppm

M: 0, 9.2, 30.4, 119.4, 274.4, 475.5 mg/kg/day

F:0, 12.9, 40.4, 162.0, 374.1, 634.8 mg/kg/day	NOAEL = 9.2 mg/kg/day

LOAEL =  30.4 mg/kg/day based on ↓body weight/ weight gain in males,
changes in clinical chemistry in both sexes (increased urea and
decreased triglycerides), and increased incidences in females of lymph
node apoptosis, thymus atrophy, and ulcer/erosion in the glandular
stomach.

870.3150

90-Day oral toxicity (dog)	45118323 (1999) 

Acceptable/guideline

0, 100, 200, 450 ppm

M: 0, 2.8, 5.8, 12.9 mg/kg/day

F: 0, 3.0, 6.2, 13.6 mg/kg/day	NOAEL = 5.8 mg/kg/day

LOAEL = 12.9 mg/kg/day based on ↑diarrhea, clinical chem. changes, and
increased incidence of thickening/ mucosal hypertrophy of the duodenum
in both sexes; body weight loss, and ↓food intake/efficiency in
females.

870.3050

28-Day oral toxicity (rat)       

	MRID 45118322 (1999) 

Acceptable/guideline

0, 20, 100, 500, 1500 ppm 

M: 0, 1.8, 9.0, 42.3, 120.2 mg/kg/day 

F: 0, 2.0 9.6, 46.6, 126.3  mg/kg/day	NOAEL =  9.0 mg/kg/day

LOAEL = 42.3 mg/kg/day based on changes in hematology parameters,
increased absolute and relative spleen weight, histopathology in spleen
and liver, in addition to increased duodenal mucosal hyperplasia in both
sexes. 

870.3200

28-Day dermal toxicity (rat)	45118324 (1999) Unacceptable/guideline (a
higher dose could be tolerated and the limit dose is 1000 mg/kg/day)

0, 40, 100, 250 mg/kg for 5 days/wk	Dermal NOAEL = 40 mg/kg/day

Dermal LOAEL = 100 mg/kg/day based on scale formation, hyperkeratosis,
and epidermal thickening.

Systemic NOAEL = 250 mg/kg/day

Systemic LOAEL > 250 mg/kg/day

The HIARC (TXR 0051553) determined that a repeat study at a higher dose
is not needed since an oral end-point (developmental toxicity NOAEL of
5.0 mg/kg/day) with a 14% dermal absorption rate yields a dermal
equivalent dose of 36 mg/kg/day (5 ÷ 0.14) which is well below the
apparent systemic toxicity NOAEL of 250 mg/kg/day in the dermal study.

870.3465

28-Day inhalation toxicity (rat)	46638801 (2005)

Acceptable/guideline

0.001, 0.030, or 0.300 mg/L for 6 hours per day, 5 days/week (20
exposure days) – Test substance was dissolved in acetone and
administered as an aerosol	Inhalation NOAEL = 0.001 mg/L (oral
equivalent dose = 0.23 mg/kg/day)

Inhalation LOAEL = 0.030 mg/L (oral equivalent dose = 6.9 mg/kg/day)
based on findings of hyperplasia in the duodenum, alveolar histiocytosis
in the lungs, and olfactory atrophy/necrosis in the nasal tissues.

870.3700a

Prenatal developmental (rat)	45118325 (1999)

Acceptable/guideline

0, 10, 25, 50 mg/kg/day	Maternal NOAEL = 10 mg/kg/day

LOAEL = 25 mg/kg/day based on ↓body wt/ wt gain and ↓food
intake/efficiency.

Developmental NOAEL = 25 mg/kg/day

LOAEL = 50 mg/kg/day based on ↑ incidences of dilated renal pelvis and
cervical ribs with no cartilage.

870.3700b

Prenatal developmental (rabbit)	45118326 and 45437001 (1999)
Acceptable/guideline

0, 1, 3, 5, 10, 20 mg/kg/day	Maternal NOAEL = 5 mg/kg/day

LOAEL = 10 mg/kg/day based on ↓ body wt gain and ↓food
intake/efficiency.

Developmental NOAEL = 5 mg/kg/day

LOAEL =10 mg/kg/day based on ↑ resorption/post-implantation loss.

870.3800

Reproduction and fertility effects

(rat)	Two Generation: MRID 45118327 (1999) Acceptable/guideline when
combined with the one generation preliminary study (below)

0, 25, 75, 300 ppm

F0 M/F: 0, 2.5/2.6, 7.4/7.8, 29.0/30.4 mg/kg/day

F1 M/F: 0, 2.8/3.0, 8.6/9.0, 35.0/36.0 mg/kg/day

One Generation: MRID 45596210 (2002)

0, 200, 400, 600 ppm

F0 M/F: 0, 20.5/21.3, 39.9/42.5, 59.1/60.4 mg/kg/day	Parental/Systemic
NOAEL = 29 mg/kg/day

LOAEL > 29 mg/kg/day based on no effects.

Reproductive NOAEL = 29 mg/kg/day

LOAEL > 29 mg/kg/day based on no effects.

Offspring NOAEL =  29 mg/kg/day

LOAEL > 29  mg/kg/day based on no effects.

Offspring NOAEL < 20.5 mg/kg/day 

Offspring LOAEL = 20.5 mg/kg/day based on decreased pup body weight and
body weight gain on and after post-natal day 7.

870.4100a

Chronic toxicity

(rat)	45118329 (1999) Unacceptable/guideline

0, 25, 75, 200 ppm 

M: 0, 1.1, 3.4, 9.0 mg/kg/day 

F: 0, 1.5, 4.6, 12.3 mg/kg/day	NOAEL =  9.0 mg/kg/day

LOAEL > 9.0 mg/kg/day.

870.4100b

Chronic toxicity (dog)	45118328 (1999)

Acceptable/guideline

0, 100, 200, 400 ppm

M: 0, 2.7, 5.4, 10.8 mg/kg/day

F: 0, 2.7, 5.4, 11.2 mg/kg/day	NOAEL = 5.4 mg/kg/day

LOAEL = 10.8 mg/kg/day based on ↑ diarrhea and clinical chemistry
changes in both sexes (decreased cholesterol, protein, albumin, and
globulin), and ↓ body weight gain and ↓food intake/efficiency in
females.

870.4200

Carcinogenicity

(rat)	45118331 (1999)

Acceptable/guideline

0, 25, 75, 200 ppm 

M: 0, 1.2, 3.4, 9.2 mg/kg/day

 

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LOAEL =  9.2 mg/kg/day based on ↓ body weight and body weight gain,
and kidney atrophy/tubular casts in both sexes; hepatic necrosis and
gross/ microscopic ulcerations/lesions in the glandular and
fore-stomachs in males.

No evidence of carcinogenicity

870.4300

Carcinogenicity

(mouse)	45118330 (1999) Unacceptable/guideline 

M: 0, 10, 30, 120 ppm 

0, 1.4, 4.1, 17.2 mg/kg/day

F: 0, 10, 30, 120, 180 ppm 

0, 1.6, 4.8, 20.5, 32.8 mg/kg/day	NOAEL =  M: 4.1 mg/kg/day

	     F:  32.8 mg/kg/day

LOAEL =  M: 17.1 mg/kg/day based on decrease in body weight gain (20%)
at 13 weeks which was supported by the results of a 90-day study.

	    F >32.8 mg/kg/day

Inadequate dosing in females based on CARC Report dated 10/22/03 (TXR #
0051445) 

No evidence of carcinogenicity

Gene Mutation

870.870.5100

Bacterial reverse mutation assay	45118332 (1997)

Acceptable/guideline	Negative  ± S9 up to 5,000 μg/plate by standard
plate and tube preincubation. No cytotoxicity at any dose but there was
precipitation at ≥2,500 μg/plate.

Gene Mutation

870.5300

Mammalian cell culture	45118335 (1998)

Acceptable/guideline	Negative  ± S9 up to cytotoxic and precipitating
concentration of 20 μg/mL

Cytogenetics (in vitro) 

870.5375 Chromosomal aberrations	45118333 (1999)

Acceptable/guideline	Negative ± S9 for clastogenic/aneugenic activity
up to 25 μg/mL.  Precipitation and cytotoxicity (reduced cell
attachment and poor quality of metaphases) were seen at concentrations
≥50  μg/mL.

Cytogenetics 

870.5395

Micronucleus test in mouse	45118334 (1998)

Acceptable/guideline	Negative for clastogenic/aneugenic activity up to
the highest dose tested (300 mg/kg).  In a preliminary study, doses
≥400 mg/kg caused death.

Unscheduled DNA synthesis

870.5550 

Rat hepatocyte culture	45118336 (1998)

Acceptable/guideline	Negative up to a cytotoxic concentration of 1.0
µg/mL. 

870.6200a

Acute neurotoxicity screening (rat)	45118337(1999)

Acceptable/guideline

0, 100, 300, 1000 mg/kg	Neurotoxicity NOAEL = 1000 mg/kg

M/F LOAEL >1000 mg/kg

Systemic M/F NOAEL = 300/〱〰洠⽧杫

M/F LOAEL 1000/ >1000 mg/kg based on ↓body weight gain in males.

870.6200b

Subchronic neurotoxicity screening (rat)	45118401 (1999)

Acceptable/guideline

0, 50, 250, 750 (M)/1500 (F) ppm

M: 0, 3.5, 16.9, 49.9 mg/kg/day

F: 0, 4.0, 20.4, 111.9 mg/kg/day	Neurotoxicity M/F NOAEL =  49.9/111.9
mg/kg/day

M/F LOAEL  >49.9/111.9 mg/kg/day.

Systemic M/F NOAEL =  16.9/20.4 mg/kg/day 

M/F LOAEL =  49.9/111.9 mg/kg/day based on ↓ body weight gain, and ↓
food intake/efficiency. 

870.7485

s

(rat)	 45118403 (1998) 

 45118404 (1999)

Acceptable/guideline	Nearly 35% of an oral dose of pyraclostrobin is
absorbed with urinary and fecal excretions accounting for about 15% and
85%, respectively, and bile elimination accounted for about 30%. Two
peak plasma concentrations were reached at 0.5-1 and 8 hours with lower
plasma concentrations in males than females (by 16-38%) during the early
peak phase.  Elimination was biphasic at a low dose with plasma half
lives of nearly 10/35 hours and monophasic at a high dose with a
half-life of nearly 20 hours.  Tissue distribution was fast, peaking at
0.5 hours, and was slightly higher among females.  Some of the highest
concentrations were found in the liver, thyroid, kidney, lung, adrenal
glands, and pancreas but all levels dropped by more than 20-fold within
72 hours. About 33 metabolites were identified in urine, feces, and bile
with no sex- or dose-related differences but the position of the label
seemed to alter the profile, particularly in the urine.  Desmethoxy
pyraclostrobin (500M07) is one of the major metabolites in rat and is
also found in large amounts in plants (BF 500-3) and livestock (500M07).
 The rat metabolic pathway included phase-I reactions such as
N-demethoxylation, various hydroxylations, and cleavage of the ether
bond with subsequent oxidation; these reactions were followed by phase
II glucuronidation and sulfation.

870.7600

Dermal penetration

(rat)	45118402 (1999) Unacceptable/guideline (most of the test material
was retained on the dressing and was unavailable for absorption;
therefore, actual dose cannot be determined. 	The HIARC calculated and
recommended a dermal penetration rate of 14% (report dated 2/10/03; TXR
# 0051553)

Page   PAGE  7  of   NUMPAGES  68