Document ID: EPA-HQ-OPP-2008-0713-0007
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-10-07T04:00Z

SEQ CHAPTER \h \r 1 

U. S. ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM

DATE:	March 16, 2009

™). 

PC Code:  099100	DP Barcode: D359197

Decision No.: 397102	Registration No.: 7969-186 & 7969-266  

Petition No.: 8F7385	Regulatory Action: Section 3

Risk Assessment Type: Single Chemical	Case No.: NA

TXR No.: NA	CAS No.: 175013-18-0

MRID No.: NA	40 CFR: 180.582

	

	

FROM:	Barry O’Keefe, Senior Biologist

		Risk Assessment Branch 3

		Health Effects Division (7509P)

THRU		Paula Deschamp, Branch Chief

		Risk Assessment Branch 3

		Health Effects Division (7509P)

TO:		Barry O’Keefe, Risk Assessor

		Risk Assessment Branch 3

		Health Effects Division (7509P)

The Registration Division has requested that HED conduct an occupational
exposure and risk assessment for new uses of pyraclostrobin on field
grown sorghum and on sorghum seed.  An aggregate human health risk
assessment will be conducted and presented in a separate HED memorandum.
 Note: This memorandum was reviewed by the Exposure Science Advisory
Committee (ExpoSAC) on March 12, 2009.

TABLE OF CONTENTS

  TOC \o "1-4" \h \z \u    HYPERLINK \l "_Toc221684421"  1.0.	EXECUTIVE
SUMMARY	  PAGEREF _Toc221684421 \h  3  

  HYPERLINK \l "_Toc221684422"  2.0.	HAZARD CHARACTERIZATION	  PAGEREF
_Toc221684422 \h  5  

  HYPERLINK \l "_Toc221684423"  2.1	Hazard Profile	  PAGEREF
_Toc221684423 \h  5  

  HYPERLINK \l "_Toc221684424"  2.2	FQPA and Uncertainty Factor
Considerations	  PAGEREF _Toc221684424 \h  6  

  HYPERLINK \l "_Toc221684425"  3.0	REGISTERED AND PROPOSED USE PATTERNS
  PAGEREF _Toc221684425 \h  7  

  HYPERLINK \l "_Toc221684426"  4.0.	OCCUPATIONAL EXPOSURE	  PAGEREF
_Toc221684426 \h  8  

  HYPERLINK \l "_Toc221684427"  4.1	Handler Exposure	  PAGEREF
_Toc221684427 \h  8  

  HYPERLINK \l "_Toc221684428"  4.1.1	Data and Assumptions for Handler
Exposure Scenarios	  PAGEREF _Toc221684428 \h  9  

  HYPERLINK \l "_Toc221684429"  4.1.2	Handlers Exposure and Risk	 
PAGEREF _Toc221684429 \h  11  

  HYPERLINK \l "_Toc221684430"  4.2	Postapplication Exposure	  PAGEREF
_Toc221684430 \h  17  

  HYPERLINK \l "_Toc221684431"  4.2.1	Data and Assumptions for
Postapplication Exposure Scenarios	  PAGEREF _Toc221684431 \h  17  

  HYPERLINK \l "_Toc221684432"  4.2.2 	Agricultural Postapplication
Exposure and Risk	  PAGEREF _Toc221684432 \h  19  

  HYPERLINK \l "_Toc221684433"  5.0	RESIDENTIAL (NON-OCCUPATIONAL)
EXPOSURE/RISK PATHWAY	  PAGEREF _Toc221684433 \h  20  

 

1.0.	EXECUTIVE SUMMARY

gs 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.

Stamina™ EPA 7969-266.  

This action will assess the use of the products Headline® (a liquid
concentrate) on sorghum and Stamina™ (a liquid concentrate) on sorghum
seeds.  Pyraclostrobin may be applied aerially, by chemigation, and by
groundboom to sorghum and with commercial seed treatment equipment to
sorghum seeds.  Based on application rates and label information,
exposure is expected to occur for short- and intermediate-term
durations.  

Hazard Characterization

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.

A NOAEL of 5 mg/kg/day was selected as the point of departure for dermal
short- and intermediate-term exposure.  The LOAEL is 10 mg/kg/day based
on prenatal developmental toxicity findings of increased resorptions in
rabbits.  Additionally, the maternal effects of decreased body weight
gain and decreased food intake and food efficiency were found at the
LOAEL of 10 mg/kg/day.  A dermal absorption factor of 14% was used to
determine dermal exposure and risk. 

A NOAEL of 0.23 mg/kg/day was selected as the point of departure for
inhalation short- and intermediate-term exposure.  The LOAEL is 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 from a
28-day inhalation study in rats.

A body weight of 60 kg is used in the dermal assessments since the point
of departure is female-specific.  For the inhalation assessment, a body
weight of 70 kg was used since point of departure is not sex-specific. 
Since the points of departure are different for dermal exposures versus
inhalation exposures, the dermal and inhalation risks are not combined.

The Agency’s level of concern for non-cancer risks (i.e., level of
concern for MOEs or Margins of Exposure) is defined by the uncertainty
factors that are applied to the assessment.  The Agency applies a 10X
factor to account for inter-species extrapolation and a 10X factor to
account for intra-species variation.  The total uncertainty factor that
is applied to occupational risk assessments is 100 for short- and
intermediate-term dermal and inhalation exposures.

  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.  Therefore, a cancer risk
assessment was not performed.

Occupational Exposure:

	Agricultural Handler Risk

MOEs greater than the level of concern (MOEs ≥ 100) at some level of
risk mitigation.  Of note, for the scenario of mixing and loading liquid
concentrates to support aerial applications, a dust mist respirator is
needed to achieve an MOE ≥ 100, which is not already included on the
proposed Headline® label.

	Seed Treatment Handler Risk

≥ 100, which is not already included on the proposed Stamina™ label.

Note:  As a condition of registration for the seed treatment uses, the
pyraclostrobin seed treatment labeling should be required to add
specific statements regarding the personal protective equipment required
for persons planting treated seed as well as other label restrictions,
as follows:.

“Seed that has been treated with this product that is then packaged or
bagged for future use must contain the following labeling on the outside
of the seed package or bag.”

"Treated Seed - Do Not Use for Food, Feed, or Oil Purposes.”

"When opening this bag or loading/pouring the treated seed, wear
long-sleeved shirt, long pants, shoes, socks, and chemical resistant
gloves."

"After the seeds have been planted, do not enter or allow worker entry
into treated areas during the restricted-entry interval (REI) of 12
hours.  Exception: Once the seeds are planted in soil or other planting
media, the Worker Protection Standard allows workers to enter the
treated area without restriction if there will be no worker contact with
the soil/media subsurface."

Review of Human Research

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

	Agricultural Postapplication Risk

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 Reentry Task Force (ARTF) database (policy # 3.1),
were used in estimating postapplication exposures.  Postapplication
risks were not a concern on day 0 (12 hours following application). 
Therefore, the restricted entry interval (REI) is based on the acute
toxicity of pyraclostrobin technical material which is classified as
Category III for acute dermal toxicity and for skin and eye irritation
potential.  Pyraclostrobin is not a dermal sensitizer.  Under the Worker
Protection Standard for Agricultural Pesticides, active ingredients
classified as acute toxicity categories III or IV for these routes are
assigned a 12-hour REI.   

As a condition of registration for the seed treatment uses, the
pyraclostrobin seed treatment labeling should be required to add
specific statements regarding the restricted-entry interval and
exceptions to the REI.

Review of Human Research:

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

Residential Exposure:

This document only presents the assessment of the proposed new
agricultural uses of pyraclostrobin.  No residential uses and no
occupational uses at residential sites are being requested in this
petition; therefore, no residential risk assessment has been conducted. 

2.0.	HAZARD CHARACTERIZATION

	2.1	Hazard Profile

There is potential for short- and intermediate-term occupational
exposure to pyraclostrobin during mixing, loading, application, and
other handling tasks and also during postapplication activities. 
Chronic exposure is not expected for the proposed uses.

For short- and intermediate-term dermal exposure, the point of departure
is from a rabbit prenatal developmental toxicity study (NOAEL = 5
mg/kg/day), based on developmental toxicity findings of increased
resorptions at 10 mg/kg/day.  Additionally, the maternal effects of
decreased body weight gain and decreased food intake and food efficiency
were found at the LOAEL of 10 mg/kg/day. Because this point of departure
is from an oral study, daily dermal doses were adjusted to account for
14% dermal absorption.  

For short-and intermediate-term inhalation exposure, the point of
departure is from a 28-day rat inhalation study (NOAEL = 0.23
mg/kg/day), based on duodenum mucosal hyperplasia and respiratory system
findings including alveolar histiocytosis and olfactory atrophy/necrosis
in nasal tissue at a LOAEL = 6.9 mg/kg/day (air concentration = 0.03
mg/L).  Because the point of departure is from an inhalation study, no
absorption adjustment factor is necessary.

A body weight of 60 kg is used in the dermal assessments since the
toxicological endpoint of concern is female-specific.  For the
inhalation assessment, a body weight of 70 kg was used since the
toxicological endpoint of concern is not sex-specific.  Since the
toxicological effects are different for dermal exposures versus
inhalation exposures, the dermal and inhalation risks are not combined.

The recent Cancer Assessment Review Committee (CARC) reevaluation
concluded that pyraclostrobin should be classified into the category
“Not likely to be Carcinogenic to Humans”. This conclusion was based
on 1) the absence of treatment-related tumor increases in both sexes of
rats and mice, which were tested at doses adequate to assess
carcinogenicity and 2) the lack of evidence of mutagenicity. 

FQPA and Uncertainty Factor Considerations

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.  The RAB3 toxicology team
previously determined 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.

The Agency’s level of concern for risks (i.e., level of concern for
MOEs or Margins of Exposure) is defined by the uncertainty factors that
are applied to the assessment.  The Agency applies a factor of 10 to
account for inter-species extrapolation to humans from the animal test
species and another factor of 10 to account for intra-species
sensitivity.  The total uncertainty factor that has been applied to
occupational risk assessments is 100 for short- and intermediate- term
dermal and inhalation risks.   

Table 1.  Acute Toxicity Data on Pyraclostrobin Technical

Guideline

 No.	

Study Type	

MRID #	

Results	

Toxicity Category

870.1100	

Acute Oral	

45118302	

LD50 =  > 5000 mg/kg	

IV

870.1200	

Acute Dermal	

45118305	

LD50 =  > 2000 mg/kg	

III

870.1300	

Acute Inhalation	

45118308	

0.31< LC50 < 1.07  mg/L	

II

870.2400	

Primary Eye Irritation	

45118311	

minimal eye irritation; MAS 4.6/110	

III

870.2500	

Primary Skin Irritation	

45118314	

moderate skin irritation; MAS 2.2/8.0	

III

870.2600	Dermal Sensitization	

45118317	

not a dermal sensitizer	

N/A

Table 2.  Summary of Toxicological Doses and Endpoints for
Pyraclostrobin Occupational Exposures

Exposure/

Scenario	Point of Departure	Uncertainty/

FQPA Safety Factors	Level of Concern (LOC) for Risk Assessment	Study and
Toxicological Effects

Dermal Short-Term (1-30 days) and 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

	LOC for MOE = 100

	Rabbit Prenatal Developmental Toxicity

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

Inhalation Short- Term (1-30 days), and Intermediate-Term (1-6 months) 
NOAEL= 0.23 mg/kg/day (air concentration = 0.001 mg/L)	UFA= 10x

UFH= 10x

	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.

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).  FQPA
SF = FQPA Safety Factor.  MOE = margin of exposure.  LOC = level of
concern.  N/A = not applicable.

3.0	REGISTERED AND PROPOSED USE PATTERNS

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 proposed
uses evaluated in this assessment are summarized in Table 3.



Table 3.  Summary of Proposed Use Pattern for Pyraclostrobin

Application  Timing, Type, and Equipment	Formulation

[EPA Reg. No.]	Application Rate 

	Maximum Application Rate 

	Preharvest Interval

(PHI)	Use Directions and Limitations

Sorghum

Foliar:

ground, aerial or through sprinkler irrigation	Headline® Fungicide
23.6% EC

(2.09 lb ai/gal)

Supplemental

Label for

7969-186	6-12 fl oz/acre	0.2 lb ai/A	N/A 

(apply no later than 25% flowering)	Do not make more than one
application of Headline® per season.  If additional fungicides are
needed, apply a labeled non-Group II fungicide with a different mode of
action.

Commercial Seed Treatment	Stamina™ BASF 500 12 F

18.4% F

(1.67 lb ai/gal)

Supplemental Label for

7969-266	0.8–1.5 fl oz/100 lb seed	0.02 lb ai/100 lb of seed	N/A	For
control of seed and seedling disease caused by Rhizoctonia solani, may
be applied in conjunction with applications of other registered seed
treatment and crop protection products.

  SEQ CHAPTER \h \r 1 4.0.	OCCUPATIONAL EXPOSURE

Pyraclostrobin is a fungicide that belongs to the strobilurin class of
chemistry. This occupational assessment will assess risks resulting from
handler and postapplication exposures resulting from use of
pyraclostrobin labeled as Headline® (liquid concentrate, 23.6% a.i.) on
field-grown sorghum and labeled as Stamina™ (liquid concentrate, 18.4%
a.i.) on sorghum seed.  

	4.1	Handler Exposure

Pyraclostrobin may be applied to sorghum foliage with aerial,
chemigation, or groundboom equipment.  Pyraclostrobin is applied to
sorghum seeds using commercial seed treatment equipment. Application
methods, rates, intervals, and use sites are summarized in Table 3. 
Handler exposure is expected to be short- or intermediate-term based on
information provided on proposed labels.  

Foliar Treatment

Occupational handlers may experience short- and intermediate-term
exposure to pyraclostrobin while mixing/loading, applying, flagging, or
performing other handler tasks to support application to sorghum.  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 are presented in Table 4.

Exposure Scenarios for Foliar Treatments

The quantitative exposure and risk assessment developed for occupational
handlers involved in application to field-grown sorghum is based on the
following exposure scenarios:

Mixing/loading liquid concentrate to support aerial applications, 

Mixing/loading liquid concentrate to support chemigation applications, 

Mixing/loading liquid concentrate to support groundboom applications,

Applying sprays with aircraft,

Applying sprays with groundboom equipment, and 

Flagging to support aerial spray applications.

Seed Treatment

Occupational handlers may experience short- and intermediate-term
exposure to pyraclostrobin while performing seed treatment activities in
commercial settings. In addition, occupational secondary handlers may
experience short- and intermediate-term exposure while planting
pyraclostrobin-treated sorghum seeds.  No chemical-specific handler
exposure data were submitted in support of this use pattern.  For
assessing seed treatment and seed planting activities, unit exposure
data were taken from HED Science Advisory Council for Exposure Policy
14: Standard Operating Procedures for Seed Treatment.  The amount of
active ingredient 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 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) Policy 15.  The
results are presented in Table 5.

Exposure Scenarios for Seed Treatments

The quantitative exposure and risk assessment developed for occupational
handlers involved in commercial application to sorghum seed is based on
the following exposure scenarios:

Loading the pesticide into seed treatment equipment and applying to
sorghum seeds (“loader/applicator”),

Loading seeds into bags (“bagger”),

Sewing seed bags (“sewer”), and 

Handlers involved in multiple commercial seed treatment activities
(“multiple activities”)

In addition, a quantitative exposure/risk assessment was developed for
occupational secondary handlers involved in planting treated sorghum
seeds.

	4.1.1	Data and Assumptions for Handler Exposure Scenarios	

Mitigation Approaches:

There are three basic risk mitigation approaches considered appropriate
for controlling occupational exposure.  These include administrative
controls, use of personal protective equipment (PPE), and the use of
engineering controls.  Occupational handler exposure assessments were
completed by HED using baseline, PPE and engineering controls.

The baseline clothing level for occupational exposure scenarios is an
individual wearing long pants, a long-sleeved shirt, shoes, socks, no
chemical-resistant gloves, and no respirator. The first level of
mitigation generally applied is PPE, which may include addition of
chemical resistant-gloves, an additional layer of clothing and/or a
respirator.  The next layer of mitigation considered in the risk
assessment process is the use of appropriate engineering controls, which
by design attempt to eliminate the possibility of human exposure. 
Examples of commonly used engineering controls include enclosed tractor
cabs or cockpits, closed mixing/loading systems, and water-soluble
packets.   

Area Treated:

Based on HED Exposure Science Advisory Committee SOP Number 9.1, the
area treated in a day for sorghum was assumed to be:

1,200 acres for mixing/loading to support aerial applications and for
applying with aircraft; 

350 acres for mixing/loading to support chemigation applications and for
flagging to support aerial treatments; and 

200 acres for mixing/loading to support groundboom applications and for
applying with groundboom equipment.

Based on HED Exposure Science Advisory Committee SOP Number 15, the
pounds of sorghum seeds treated or planted in a day was assumed to be:

718,000 pounds of sorghum seed treated per day at a commercial seed
treatment site; 

12,000 pounds of sorghum seed planted per day

Application Rate:

The maximum application rate for each proposed use is summarized in
Table 3. 

Body Weight:

The average adult body weight of 60 kg was used for estimating dermal
dose, since the toxicological effects are from a reproductive study.  

The average adult body weight of 70 kg for estimating inhalation dose.

Absorption Factor:

Since the adult dermal endpoint was based on an oral study, a 14% dermal
absorption factor was used to estimate dermal exposure.    

Since the adult inhalation endpoint was not based on an inhalation
study, no inhalation absorption factor is needed to estimate inhalation
exposure.  

Equations and Calculations:

Daily Dose:  Daily dose (inhalation or dermal) was calculated by
normalizing the daily dermal or inhalation exposure value by body weight
and accounting for dermal absorption. 

Daily Dose (mg/kg/day) = Daily Exposure (mg ai/day) x {Absorption Factor
(%/100)}

                                                                        
                      Body Weight (kg)  

Where:

	Average Daily Dose = 	Absorbed dose received from exposure to a
pesticide in a given scenario

				 (mg pesticide active ingredient/kg body weight/day)

	Daily Exposure 	=	Amount (mg ai/day) deposited on the surface of the
skin that is available for

				 dermal absorption or amount inhaled that is available for
inhalation absorption;

	Absorption Factor = 	A measure of the amount of chemical that crosses a
biological boundary such as

				the skin or lungs 

	Body Weight 	= 	Body weight determined to represent the population of
interest in a risk

				assessment

Margin of Exposure (MOE): The calculations of daily dermal dose and
daily inhalation dose received by handlers were then compared to the
appropriate point of departure (i.e., NOAEL) to assess the total risk to
handlers for each exposure route within the scenarios. All risks were
calculated separately for dermal and inhalation exposure levels using
the following formula:

		MOE = 	______NOAEL (mg/kg/day)____      

				Average Daily Dose (mg/kg/day)

Where:

MOE   =	Margin of exposure value used by HED to represent risk or how
close a chemical exposure is to being a concern (unitless)

	ADD =		Average daily dose (ADD) is absorbed dose received from exposure
to pesticide

	NOAEL	 =	Dose level in a toxicity study, where no observed adverse
effects occurred in the study

Handlers Exposure and Risk

HED’s level of concern for the MOE is defined by the uncertainty
factors that are applied to the assessment.  HED applies a 10X factor to
account for inter-species extrapolation and a 10X factor to account for
intra-species sensitivity.  The total uncertainty factor that has been
applied to the non-cancer risk assessment for pyraclostrobin is 100 for
occupational exposure.  Occupational exposure and risk resulting in MOEs
greater than or equal to 100 will not be of concern to HED.

Agricultural Handlers

Summaries of the exposures and risks for handlers involved in
application to field-grown sorghum are included in Table 4.  The maximum
application rate for each exposure scenario is presented as the worst
case scenario.  All handler scenarios resulted in MOEs greater than the
level of concern (MOEs ≥ 100) at some level of mitigation. 

The dermal risks to handlers are not a concern with baseline attire
(i.e., long-sleeve shirt, long pants, shoes, and socks) for the
following scenarios:

applying sprays with groundboom equipment, and

flagging to support aerial spray applications.

If chemical-resistant gloves are worn in addition to baseline attire,
the dermal risks are not a concern for the following scenarios:

mixing and loading liquid concentrates to support aerial applications, 

mixing and loading liquid concentrates to support chemigation, and 

mixing and loading liquid concentrates to support groundboom
applications.

The inhalation risks to handlers are not a concern with baseline attire
(no respirator) for the following scenarios:

mixing and loading liquid concentrates to support chemigation; 

mixing and loading liquid concentrates to support groundboom
applications;

applying sprays with groundboom equipment; and

flagging to support aerial spray applications.

If a respirator is worn, the inhalation risks are not a concern for the
following scenario:

mixing and loading liquid concentrates to support aerial applications.

Note:  The respirator unit exposure value represents a NIOSH-approved
respirator with a dust-mist filter with MSHA/NIOSH approval number
prefix TC-21 or any N, R, P, or HE filter.  Such a respirator is
generally referred to as an 80% protection factor respirator, or a
“quarter-face, cup-style dust/mist filtering respirator”.

Only engineering control (enclosed cockpit) data are available to assess
dermal and inhalation risks to handlers operating aircraft.  The risks
are not a concern for pilots using enclosed cockpits and wearing
baseline attire and no respirator.

Commercial Seed Treatment Handlers

Summaries of the exposures and risks for handlers involved in commercial
application to sorghum seed and planting treated sorghum seed are
included in Table 5.  The maximum application rate for each exposure
scenario is presented as the worst case scenario.  All seed treatment
activities result in MOEs greater than the LOC of 100 and are not of
concern at some level of risk mitigation.  

The dermal risks to handlers are not a concern with baseline attire
(i.e., long-sleeve shirt, long pants, shoes, and socks) for the
following scenarios:

loading treated seeds into bags (“bagger”), and

sewing the bags of seed (“sewer”)

There are no data to estimate dermal exposure and risk at baseline
attire for the following scenarios:

loading the pesticide into seed treatment equipment and applying to
sorghum seeds (“loader/applicator”); 

handlers involved in multiple commercial seed treatment activities
(“multiple activities”); and

planting treated seeds (“planter”).

The dermal risks are not a concern at baseline attire plus
chemical-resistant gloves for these scenarios.

The inhalation risks to handlers are not a concern at baseline attire
(no respirator) for the following scenarios:

loading the pesticide into seed treatment equipment and applying to
sorghum seeds (“loader/applicator”);

loading treated seeds into bags (“bagger”); 

sewing the bags of seed (“sewer”); and

planting treated seeds (“planter”).

If a respirator is worn in addition to baseline attire, inhalation risk
is not a concern for the following scenario:

handlers involved in multiple commercial seed treatment activities
(“multiple activities”).

Note:  The respirator unit exposure value represents a NIOSH-approved
respirator with a dust-mist filter with MSHA/NIOSH approval number
prefix TC-21 or any N, R, P, or HE filter.  Such a respirator is
generally referred to as an 80% protection factor respirator, or a
“quarter-face, cup-style dust/mist filtering respirator”.



Table 4.  Pyraclostrobin Agricultural Handler Exposures and Risks

Exposure Scenario	Crop and Product	App. Ratea 

(lb ai/acre)	Area Treated Dailyb (acres) 	Unit Exposuresc	Dermal Dosesd
and MOEse

(LOC MOE = 100)	Inhalation Dosesfand MOEsg

(LOC MOE = 100)

Baseline Dermal (mg/lb ai)	Baseline Inhalation (µg/lb ai)	Baseline
Dermal Plus Gloves

(mg/lb ai)	Inhalation 80% PF (µg/lb ai)	Baseline Doseh

mg/kg/day	Baseline MOE  	 PPE-G Dosei

mg/kg/day 	PPE-G MOE 	Baseline Dose

mg/kg/day	Baseline MOE  	D-M Respirator

Dosej

mg/kg/day	D-M Respirator MOE

Mixing/Loading Liquid Concentrates for Aerial Application	Sorghum	0.2
1,200	2.9	1.2	0.023	0.24	1.6	3.1	0.013	390	0.0041	56	0.00082	280

Mixing/Loading Liquid Concentrates for Chemigation Applications

0.2	350	2.9	1.2	0.023	0.24	0.47	11	0.0038	1,300	0.0012	190	0.00024	960

Mixing/Loading Liquid Concentrates for Groundboom Applications

0.2	200	2.9	1.2	0.023	0.24	0.27	18	0.0021	2,300	0.00069	340	0.00014
1,700

Applying Sprays via Aerial Equipmentk

0.2	1,200	0.005 (Eng. Cont.)	0.068 (Eng. Cont.)	NA	NA	0.0028

(Eng. Cont.)	1,800

(Eng. Cont.)	NA	NA	0.00023 (Eng. Cont.)	990

(Eng. Cont.)	NA	NA

Applying Sprays via Groundboom

0.2	200	0.014	0.74	0.014	0.148	0.0013	3,800	0.0013	3,800	0.00042	540
0.000085	2,700

Flagging for Aerial Spray Applications

0.2	350	0.011	0.35	NA	0.07	0.0018	2,800	NA	NA	0.00035	660	0.00007	3,300

a. Application Rates based on proposed supplemental label for EPA Reg.
No. 7969-186.  

b. Science Advisory Council Policy # 9.1

c. Unit Exposures based on PHED Version 1.1

d. Dermal Dose  (mg/kg/day)  = daily unit exposure (mg/lb ai)  x
application rate (lb ai/acre) x acres treated * dermal absorption (14%)
/ body weight (60 kg adult female).

e. Dermal MOE = NOAEL (5.0 mg/kg/day) / dermal daily dose (mg/kg/day). 
Level of concern = 100.

f. Inhalation Dose (mg/kg/day) =  daily unit exposure (μg/lb ai)  x
application rate (lb ai/acre) x acres treated * inhalation absorption
(100%)  x conversion factor (1 mg/1,000 μg) / body weight (70 kg).  

g. Inhalation MOE = NOAEL (0.23 mg/kg/day) / inhalation daily dose
(mg/kg/day). Level of concern = 100.

h. Baseline Dermal:  Long-sleeve shirt, long pants, and no gloves;
Baseline Inhalation: no respirator.

i. Baseline plus Gloves Dermal: Baseline plus chemical-resistant gloves.

j. D/M: The respirator unit exposure value represents a NIOSH-approved
quarter-face, cup style dust/mist filtering respirator (e.g., dust
mask), which is considered to provide an 80% reduction in inhalation
exposure.

k. Only engineering control (enclosed cockpit) data are available to
assess dermal and inhalation risks to handlers operating aircraft.  

Table 5. Pyraclostrobin Seed Treatment Handler Exposures and Risks

Exposure Scenario	lbs seed treated or planted per daya	Appl. Rateb 

(lb ai/100 lb	Unit Exposuresc 	Dermal Dosesg and MOEsh

(LOC MOE = 100)	Inhalation Dosesi and MOEsj

(LOC MOE = 100)

	Dermal Baselined (mg/lb ai) 	Dermal PPE-Ge (mg/lb ai) 	Inhalation
Baselinef (µg/lb ai)	D-M Respirator

(µg/lb ai)	Baseline Dose	Baseline MOE  	 PPE-G Dose 	PPE-G MOE 
Baseline Dose	Baseline MOE  	D-M Respirator

Dose	D-M Respirator MOE

Sorghum

Loader/ Applicator	718,000	0.02	No Data	0.023	0.34	0.068	No Data	No Data
7.70E-3	650	6.97E-4	330	1.39E-4	1,600

Sewer

	0.0062	No Data	0.23	0.046	2.10E-3	2,400	No Data	No Data	4.72E-4	490
9.44E-5	2,400

Bagger

	0.0091	No Data	0.16	0.032	3.00E-3	3,600	No Data	No Data	3.28E-4	700
6.56E-5	3,500

Multiple Activities

	No Data	0.042	1.6	0.32	No Data	No Data	1.40E-2	360	3.28E-3	70	6.56E-4
350

Planter 

(Secondary Handler)	12,000	0.02	No Data	0.25	3.4	0.68	No Data	No Data
1.40E-3	3,600	1.20E-4	2,000	2.72E-5	8,500

The amount of seed treated or planted per day are HED estimates based on
HED Science Advisory Council for Exposure Policy 15:  Amount of Seed
Treated or Planted per Day, March 2, 2004, and values submitted by
industry. 

Application rates are the maximum application rates determined from
proposed labels for pyraclostrobin.

The unit exposures are from HED Science Advisory Council for Exposure
Policy 14: Standard Operating Procedures for Seed Treatment. For the
tuberous and corm vegetable commercial seed treatment scenario, however,
the unit exposures are from the Pesticide Handlers Exposure Database
(PHED) Version 1.

Dermal Baseline:  Long-sleeve shirt, long pants, and no gloves.

Dermal PPE-G: Baseline plus chemical-resistant gloves.

Inhalation Baseline: no respirator.

D/M: The respirator unit exposure value represents a NIOSH-approved
quarter-face, cup style dust/mist filtering respirator (e.g., dust
mask), which is considered to provide an 80% reduction in inhalation
exposure.

h. 	Dermal Dose (mg/kg/day) = daily unit exposure (mg/lb ai) x
application rate (lb ai/lb seed) x lbs seed treated or planted per day x
dermal absorption (14%) / body weight (60 kg, adult female).

i. 	Dermal MOE = NOAEL (5 mg/kg/day) / dermal daily dose (mg/kg/day). 
Level of concern = 100.

Inhalation daily dose (mg/kg/day) = daily unit exposure (μg/lb ai)  x
(lb ai/lb seed) x lbs seed treated or planted per day x conversion
factor (1 mg/1,000 μg) / body weight (70 kg).

k.	Inhalation MOE = NOAEL (0.23 mg/kg/day) / inhalation daily dose
(mg/kg/day). Level of concern = 100.

  SEQ CHAPTER \h \r 1 Postapplication Exposure

4.2.1	Data and Assumptions for Postapplication Exposure Scenarios	

One of the proposed uses for pyraclostrobin involves foliar applications
to field-grown sorghum.  Therefore, postapplication exposure is possible
for workers entering treated fields for activities such as scouting,
irrigating, and hand weeding.  There are also potential postapplication
exposures to workers entering fields after pyraclostrobin-treated
sorghum seeds are planted.

HED assumes that inhalation exposures are minimal compared to dermal
exposures following outdoor applications of an active ingredient with
low vapor pressure.  Since pyraclostrobin is applied only in outdoor
settings and has a very low vapor pressure, postapplication inhalation
exposures and risks were not assessed.

Postapplication dermal exposure and risk was estimated. 
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 6. 

The DFR data were used to estimate restricted entry intervals (REIs) by
extrapolating to the proposed use on sorghum.  It was found that the
type of formulation used influences the DFR profile.  Since the proposed
product is an EC formulation, the DFR data for the liquid concentrate
formulations were considered.  Average percent initial DFR values were
calculated (i.e., 18% for liquid concentrates) and used to estimate
surrogate residue values for field-grown sorghum.  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 residue values 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).

Table 6.  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. 

Equations/Calculations:

The following equations were used to calculate risks for workers
performing postapplication activities:

DFRt (µg/cm2)	=	AR (lb ai/acre) x F x (1-D)t x 4.54E8  µg/lb x 24.7E-9
acre/cm2

	Where:	

	DFRt 	=	dislodgeable foliage residue on day "t" (µg/cm2)

          	AR	=	application rate (lb ai/acre)

	F	=	fraction of ai retained on foliage (unitless)

	D	=	fraction of residue that dissipates daily (unitless)

and

Daily dermal dose t (mg/kg-day) = DFRt (µg/cm2) x 1E-3 mg/µg x Tc
(cm2/hr) x DA x ET (hrs)									BW (kg)

	Where,

	t	= 	number of days after application day (days)

	DFRt 	=	dislodgeable foliage residue on day "t" (µg/cm2)

	Tc	=	transfer coefficient (cm2/hr)					

     	DA	=     	dermal absorption factor (unitless)

	ET	=	exposure time (hr/day)

	BW	=	body weight (kg)

		4.2.2 Agricultural Postapplication Exposure and Risk

The postapplication exposure and risk associated with sorghum crops is
summarized in Table 7.  All scenarios resulted in MOEs greater than 100
on day 0 (12 hours after application), and therefore are not of concern
to HED.  Since the postapplication risks are not a concern on Day 0 (12
hours following application), the restricted entry interval (REI) is
based on the acute toxicity of pyraclostrobin technical material which
is classified as Category III for acute dermal toxicity and for skin and
eye irritation potential.  Pyraclostrobin is not a dermal sensitizer. 
Under the Worker Protection Standard for Agricultural Pesticides, the
default restricted-entry interval is 12 hours for active ingredients
classified as acute toxicity categories III or IV for these routes of
entry. 

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ective for workers entering fields following planting of treated seeds. 
Note:  a standard WPS exception to this REI states that once seeds are
planted in soil or other planting media, the Worker Protection Standard
allows workers to enter the treated area without restriction if there
will be no worker contact with the seeds or the soil/media subsurface.

As a condition of registration for the seed treatment uses, the
pyraclostrobin labeling should state:

“Seed that has been treated with this product that is then packaged or
bagged for future use must contain the following labeling on the outside
of the seed package or bag.”

"Treated Seed - Do Not Use for Food, Feed, or Oil Purposes.”

"When opening this bag or loading/pouring the treated seed, wear
long-sleeved shirt, long pants, shoes, socks, and chemical resistant
gloves."

"After the seeds have been planted, do not enter or allow worker entry
into treated areas during the restricted-entry interval (REI) of 12
hours.  Exception: Once the seeds are planted in soil or other planting
media, the Worker Protection Standard allows workers to enter the
treated area without restriction if there will be no worker contact with
the soil/media subsurface."

Table 7.  Summary of Postapplication Risks for Proposed Use on
Field-Grown Sorghum

Crop	Application Rate

(lb ai/A) 1	DAT 2	DFR 3

(μg/cm2)	TC 4

(cm2/hr)	Activity 4	Short- & Intermediate-Term Dose5	Short- &
Intermediate-Term MOE 6

Sorghum 	0.20	0	0.404	100	Scouting and hand weeding of low  growth
foliage plants	0.00075	6,600

1,000	Irrigating and scouting of high growth foliage plants	0.0075	660

Maximum application rate indicated on proposed label (see Table 3). 

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.  

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 6, used LC average [18%] ).  This data was derived from summaries
of results presented in MRIDs 45118727, 45118724, 45118726, and 45118728
and 45118729.

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

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.

MOE = NOAEL/Daily Dose

RESIDENTIAL (NON-OCCUPATIONAL) EXPOSURE/RISK PATHWAY

This document only presents the assessment of the proposed new
agricultural and commercial seed treatment uses of pyraclostrobin.  No
residential uses and no occupational uses at residential sites are being
requested in this petition; therefore, no residential risk assessment
has been 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 database 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.

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