                 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                         WASHINGTON, D.C. 20460      

                                                	OFFICE OF CHEMICAL SAFETY AND 
	POLLUTION PREVENTION                                                                                 
	



MEMORANDUM

Date:	January 20, 2011

SUBJECT:	Fluoxastrobin:  Occupational and Residential Exposure Assessment for proposed agricultural uses of fluoxastrobin on Squash and Cucumber Crop Subgroup 9B (Chayote; Chinese waxgourd; Cucumber; Gherkin; Gourd, edible; Pumpkin; Squash, summer; and Squash, winter).

PC Code: 028869
DP Barcode: 380848
Decision No.: 433137
Registration No.:  66330-64,
Petition No.: 0F7726
Regulatory Action: Section 3
Risk Assessment Type: Single Chemical
Case No.: NA
TXR No.: NA
CAS No.:  193740-76-0
MRID No.: NA
40 CFR: 180.609

FROM:		Kristin Rury, Biologist
			Risk Assessment Branch 3
			Health Effects Division (7509P)

THROUGH:		Barry O'Keefe, Senior Biologist
			Risk Assessment Branch 3
			Health Effects Division (7509P)

TO:			Nancy Tsaur, Risk Assessor
			Risk Assessment Branch 3
			Health Effects Division (7509P)

The Registration Division (RD) requested that the Health Effects Division (HED) conduct an occupational exposure and risk assessment for new proposed uses of fluoxastrobin on squash and cucumber.  Note: This memorandum was reviewed by the Exposure Science Advisory Committee (ExpoSAC) on January 20, 2011.

1.0	EXECUTIVE SUMMARY

Fluoxastrobin is a strobilurin class active ingredient (ai) that is proposed for use as a broad-spectrum fungicide.  The new proposed uses of fluoxastrobin are for control of certain diseases on squash and cucumber crop subgroup 9B (Chayote; Chinese waxgourd; Cucumber; Gherkin; Gourd, edible; Pumpkin; Squash, summer; and Squash, winter). The proposed formulated end-use product evaluated in this assessment is labeled under the trade name Fluoxastrobin 480 SC Fungicide (EPA Reg. No. 66330-64), which contains 40.3% (i.e., 4 lbs ai/gallon) fluoxastrobin, and serves as the master label for Evito(R) 480 SC fungicide, DISARM(TM) 480 SC Fungicide, and Fluoxastrobin 480 SC Fungicide Seed Treatment, produced by Arysta LifeScience North America, LLC (Arysta).  In this memorandum, the name fluoxastrobin will be used for the ai in this product.

Proposed Use Profile:
Broadcast foliar applications of fluoxastrobin may be applied to squash and cucumber crop subgroup 9B at a maximum application rate of 0.16 lb ai/A for both foliar and soil-borne diseases.  For all of crop subgroup 9B, handlers may apply fluoxastrobin using groundboom equipment only.  The maximum application rate is 0.68 lb ai per year with a maximum of 4 applications per season and a minimum application interval of 7 days between applications.  

Exposure Profile:
There is a potential for short- and intermediate-term occupational exposure to fluoxastrobin during mixing, loading, application, and other handling tasks and for short- and intermediate-term occupational exposure during post-application activities. Chronic exposure is not expected for the proposed use patterns associated with fluoxastrobin.  

Hazard Profile:  
A short-term dermal endpoint was not identified; therefore, only intermediate-term dermal risks as well as short- and intermediate-term inhalation risks were assessed.  The estimated dermal and inhalation exposures were compared to the oral No Observed Adverse Effect Level (NOAEL) of 3.0 mg/kg/day from a 90 day subchronic feeding dog study in which dose-related reductions in net body weight gain and food efficiency, in addition to toxicity findings in the liver (cholestasis) of both sexes, and kidneys (increased relative weights in females and degeneration of the proximal tubular epithelium in males), were observed at the Lowest Observed Adverse Effect Level (LOAEL) of 24.8 mg/kg/day for males and 24.2 mg/kg/day for females.  Because this endpoint is from an oral study, the estimated dermal exposures were adjusted by applying a 2.3% dermal absorption factor.  Since no inhalation absorption data are available, toxicity by the inhalation route is considered to be equivalent to the estimated toxicity by the oral route of exposure.  This endpoint is not a developmental effect; therefore, a 70-kg body weight was used in the calculations.  Resulting intermediate-term risk estimates were combined into total risk estimates because the same endpoint was chosen to evaluate both routes of exposure.  The level of concern (LOC) for occupational risk is for margins of exposure (MOEs) of 100 (i.e., an MOE < 100 is of concern).  Fluoxastrobin is characterized as "not likely to be carcinogenic to humans" based on the lack of increased tumor incidence in the rat and mouse carcinogenicity studies; therefore, cancer risks were not assessed.

Occupational Exposure & Risk Estimates:
	Agricultural Handlers:
No chemical-specific handler exposure data were submitted in support of this registration.  It is the policy of 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 for regulatory actions when chemical-specific monitoring data are not available (HED ExpoSAC Standard Operating Procedure (SOP) No. 7, dated 1/28/99).  The results of the occupational handler exposure and risk assessment indicate that MOEs were greater than the level of concern (LOC = 100) at some level of risk mitigation.  

Dermal
For all handler mixing, loading, and applying scenarios, the intermediate-term dermal risks do not exceed HED's level of concern with baseline attire (i.e., long-sleeve shirt, long pants, shoes, and socks) or baseline attire plus chemical resistant gloves.  With baseline attire, the dermal MOE for mixer/loaders was 250, and the MOE for applicators was 17,000.  With baseline attire plus chemical resistant gloves, the dermal MOE for mixer/loaders was 31,000 and the MOE for applicators was 51,000.  

Inhalation
The short- and intermediate-term inhalation risks to handlers do not exceed HED's level of concern at baseline (no respirator) for any of the handler scenarios.  With baseline attire (no respirator) the inhalation MOE for mixer loaders was 14,000 and the MOE for applicators was 22,000,000.  

Combined
Combined dermal and inhalation risks do not exceed HED's level of concern with baseline attire or baseline attire plus chemical resistant gloves. With baseline attire, the combined (dermal + inhalation) MOE for mixer/loaders was 240 and the MOE for applicators was 17,000.  With baseline attire plus chemical resistant gloves, the combined (dermal + inhalation) MOE was 9,500 for mixer/loaders and 51,000 for applicators.  

	Agricultural Post-Application:
Based on HED's current practices, a quantitative occupational post-application inhalation exposure assessment was not performed for fluoxastrobin at this time.  However, there are multiple potential sources of post-application inhalation exposure to individuals performing post-application activities in previously treated fields.  If new policies or procedures are put into place, HED may revisit the need for a quantitative occupational post-application inhalation exposure assessment for fluoxastrobin.

Intermediate-term dermal post-application exposures and risks to occupational workers were estimated using standard values established by HED since no chemical-specific data were submitted.  Using HED default assumptions and default DFR values, all scenarios resulted in MOEs greater than 100 on day 0 (12 hours after application), and therefore, risks do not exceed HED's level of concern.  
      
The restricted entry interval (REI) is currently based on the acute toxicity of fluoxastrobin technical material.  Fluoxastrobin is classified as Toxicity Category III by the dermal route and for eye irritation potential and Toxicity Category IV for skin irritation potential.  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.  Therefore, the 12-hour REI that appears on the proposed label is adequate for protection of the exposed workers.

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 PHED, have been determined to require a review of their ethical conduct and have received that review.

Residential Exposure:
This document presents the assessment of proposed agricultural uses of fluoxastrobin.  No residential uses are being requested at this time; therefore, no residential handler exposure and risk assessment has been conducted in this document.  However, uses on turf and ornamentals are currently registered on fluoxastrobin labels.

2.0	HAZARD CHARACTERIZATION

The quality of the toxicology database for fluoxastrobin is good and the confidence in the hazard and dose-response assessments is high.  The toxicity database for fluoxastrobin is considered adequate to support toxicity endpoint selection for risk assessment and for FQPA evaluation.  However, under the current 40 CFR §158.500 data requirement guidelines, the immunotoxicity data (OPPTS 780.7800) is required as a condition of registration.  HED determined that the 10X FQPA safety factor for the protection of infants and children should be removed for all potential exposure scenarios to fluoxastrobin because the toxicity database is adequate, there are no residual uncertainties for pre- and/or postnatal toxicity, and the doses chosen as quantitative risk estimates are adequately protective for infants and children.  Additionally, 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.  

To address the immunotoxicity data requirements as presented in the 40 CFR Part 158, HED examined the entire toxicity database of fluoxastrobin; the database of this chemical does not show clear evidence of biologically relevant effects on the immune system that relate to this chemical.  The overall weight of evidence suggests that this chemical does not directly target the immune system.  An immunotoxicity study in the mouse is available; the results of this study show no apparent decrease on B-cell activated, T-cell mediated IgM response to sheep red blood cell (SRBC) at doses as high as 2383 mg/kg/day. However, this study has many deficiencies including uncertainty in dietary test material intake, and the study is classified as unacceptable. At this time, HED does not believe that conducting a new functional immunotoxicity study will result in a lower NOAEL than the regulatory dose for risk assessment, and an additional factor for database uncertainty (UFDB) is not needed to account for lack of this study.

HED's LOC for the MOE is defined by the uncertainty factors that are applied to the assessment.  HED applies a 10X factor to account for interspecies extrapolation and a 10X factor to account for intraspecies sensitivity.  The total uncertainty factor that has been applied to the non-cancer risk assessment for fluoxastrobin is 100 for occupational exposure.  Occupational exposure and risk resulting in MOEs greater than or equal to 100x will not exceed HED's level of concern.

The acute toxicity for fluoxastrobin is summarized in Table 1.  Fluoxastrobin has a low order of acute toxicity based on its classification in Toxicity Category III via the oral and dermal routes, and Toxicity Category IV by the inhalation route of exposure.  Fluoxastrobin is a moderate eye irritant (Toxicity Category III), but is neither a dermal irritant nor a sensitizer.

               Table 1:  Acute Toxicity Profile - Fluoxastrobin
                                 Guideline No.
                                  Study Type
                                    MRID(s)
                                    Results
                               Toxicity Category
                                   870.1100
                               Acute oral - rat
                                   45865612
                              LD50>2000 mg/kg
                                      III
                                   870.1200
                              Acute dermal - rat
                                   45865613
                              LD50>2000 mg/kg
                                      III
                                   870.1300
                            Acute inhalation  - rat
                                   45865618
                                LC50 = 4.9 mg/L
                                      IV
                                   870.2400
                         Acute eye irritation - rabbit
                                   45865620
                               moderate irritant
                                      III
                                   870.2500
                       Acute dermal irritation  - rabbit
                                   45865622
                                not an irritant
                                      IV
                                   870.2600
                        Skin sensitization - guinea pig
                                   45865624
                               not a sensitizer
                                       -

Exposures to occupational handlers are expected to be short- and intermediate-term in duration via the dermal and inhalation routes.  Exposures to occupational post-application workers are expected to be short- and intermediate-term in duration via the dermal route.  A short-term dermal endpoint was not identified; therefore, only intermediate-term dermal risks were assessed.  For the other routes of exposure, the same point of departure (PoD) was  selected from a 90-day subchronic dog study (i.e., NOAEL of 3 mg/kg/day), based on dose-related reductions in net body weight gain and food efficiency in addition to toxicity findings in the liver (cholestasis) in both sexes and kidneys (increased relative weights in females and degeneration of the proximal tubular epithelium in males).  Because this is an oral study, dermal doses were adjusted to account for 2.3% dermal absorption, and inhalation doses were calculated assuming 100% absorption.  Resulting dermal and inhalation MOEs were combined into total MOEs because the same endpoint was chosen to evaluate both routes of exposure.  The endpoints and PoDs selected for fluoxastrobin are shown in Table 2.  

Table 2:	 Summary of Toxicological Doses & Endpoints for Fluoxastrobin for Use in Occupational Risk Assessments
                                   Exposure
                                   Scenario
                              Point of Departure
             Uncertainty/FQPA Safety Factors and Level of Concern
                        Study and Toxicological Effects
Dermal 
Short-Term
(1 - 30 days)
N/A


None
None: A 28-day dermal toxicity study in the rat is negative up to the limit dose and there are no developmental or neurotoxicity concerns
Dermal 
Intermediate-Term
(1 - 6 months)
NOAEL = 3.0 mg/kg/day           

dermal absorption rate = 2.3%
UFA = 10X
UFH = 10X
FQPA SF = 1X
LOC for MOE = 100
90 Day Subchronic Dog
LOAEL =  M/F 24.8/24.2 mg/kg/day (800 ppm) based on dose-related reductions in net body weight gain and food efficiency in addition to toxicity findings in the liver (cholestasis) in both sexes and kidneys (increased relative weights in females and degeneration of the proximal tubular epithelium in males).
Inhalation 
Short-Term
(1 - 30 days) and 
Intermediate-Term
(1 - 6 months)
NOAEL = 3 .0 mg/kg/day 

Inhalation absorption rate = 100%

UFA = 10X
UFH = 10X
FQPA SF = 1X
LOC for MOE = 100
90 Day Subchronic Dog
LOAEL =  M/F 24.8/24.2 mg/kg/day (800 ppm) based on dose-related reductions in net body weight gain and food efficiency in addition to toxicity findings in the liver (cholestasis) in both sexes and kidneys (increased relative weights in females and degeneration of the proximal tubular epithelium in males).
Cancer (oral, dermal, inhalation)
Classification: Not Likely to be carcinogenic to humans.
NOAEL = no observed adverse effect level.  LOAEL = lowest observed adverse effect level.  FQPA SF = FQPA Safety Factor.  UF = uncertainty factor.  UFA = extrapolation from animal to human (intra-species).  UFH = potential variation in sensitivity among members of the human population (inter-species).  MOE = margin of exposure.  LOC = level of concern.  N/A = not applicable.

3.0	PROPOSED USE PATTERNS

Table 3 provides a summary of the proposed uses of fluoxastrobin.








     Table 3: Use Profile for Fluoxastrobin for use on Squash and Cucumber
                                     Crop
                              Product Information
                                 Application 
                             Method of Application
                   Maximum Single Application Rate (lb ai/A)
                      Maximum Number of Applications (oz)
                          Retreatment Interval (RTI)
                       Maximum Seasonal Application Rate
Squash/Cucumber Crop Subgroup 9B (Chayote; Chinese waxgourd; Cucumber; Gherkin; Gourd, edible; Pumpkin; Squash, summer; and Squash, winter)
EVITO(R) 480 SC Fungicide EPA Reg. No.  66330-64, 4 lb fluoxastrobin per gallon
                                Foliar Disease
                                Groundboom Only
                                     0.16
                                       4
                                   7-14 days
                                     0.68


                              Soilborne Disease 



                                    7 days


4.0	OCCUPATIONAL EXPOSURE/RISK PATHWAY

	4.1 	Handler Exposure

Fluoxastrobin can be applied to crop subgroup 9B using groundboom application equipment.  Application methods, maximum application rates, 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.  

The quantitative exposure/risk assessment for occupational handlers is based on the following exposure scenarios: 

Mixer/Loaders:
   1. Mixing/loading liquid concentrate to support groundboom applications, and
      
Applicators:
   2. Applying sprays with groundboom equipment.
      
		4.1.1	Data and Assumptions for Handler Exposure Scenarios	

Unit Exposures:
Chemical-specific data for assessing exposure during pesticide handling activities (mixing/loading, and applying) were not submitted to the Agency in support of this Section 3 application.  It is HED policy to use data from the PHED Version 1.1 to assess handler exposures for regulatory actions when chemical-specific data are not available (ExpoSAC, SOP No.7, January 1999).

Mitigation Approaches:
The baseline clothing level for occupational exposure scenarios is generally 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 personal protective equipment (PPE), which may include addition of chemical resistant-gloves (as specified on the proposed label), 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 cockpits or tractor cabs, closed mixing/loading systems, and water-soluble packets.

Occupational handler exposure assessments were completed by HED using baseline clothing attire, and baseline clothing attire plus gloves.

Area Treated:
Based on HED ExpoSAC SOP No. 9.1, the area treated in a day was assumed to be 80 acres for mixing, loading and applying fluoxastrobin with groundboom equipment to crop subgroup 9B.

Application Rate:
Broadcast foliar applications of fluoxastrobin may be applied at a maximum application rate of 0.16 lb ai/A for crop subgroup 9B.  Application rates are shown in Table 3. 
   
Body Weight:
The average adult body weight of 70 kg was used for estimating dermal and inhalation doses, since the selected toxicological endpoints are not based on a developmental effect.

Absorption Factors:
Since the intermediate-term dermal endpoint was based on an oral study (90 day subchronic feeding study in the dog), a dermal absorption factor of 2.3% was used to estimate dermal exposure for intermediate-term durations.  The results of a preliminary dermal study (MRID 45911501) clearly showed that following intravenous administration, fluoxastrobin is rapidly and nearly totally excreted in the urine and feces within 48 hours (allowing for 100% bioavailability).  Following an 8-hour dermal application in a male monkey, absorption was negligible (1.16% preliminary, 2.16% main).  The normalized absorption value for the main study (MRID 45911502) was 2.31%.  Therefore, HED set the dermal absorption value at 2.3% for risk assessment purposes.

Since the short- and intermediate-term inhalation endpoint was based on an oral study (90 day subchronic feeding study in the dog) and no inhalation absorption data are available, toxicity by the inhalation route is considered to be equivalent to the estimated toxicity by the oral route of exposure (100% absorption factor). 

Equations and Calculations:

Daily Exposure: Daily handler exposures are estimated for each applicable handler task with the application rate, the amount of acres treated in a day, and the applicable unit exposure using the following formula:


      Daily Exposure (mg ai/day) = Unit Exposure (ug ai/lb ai handled) x Application Rate (lbs ai/) x Daily Amount Handled (lbs/day) x Conversion Factor (mg/1,000 ug)

	Where:  

	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,
       Unit Exposure =		Unit exposure value (ug ai/day),
      Application Rate =	Normalized application rate based on a logical unit treatment, such as acres; maximum values are used (lb ai/acre), and
      Daily Amount Handled =   Normalized application area based on a logical unit treatment such as acres (A/day). 

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 and inhalation absorption. 
   
      Average Daily Dose (mg/kg/day) = Daily Exposure (mg ai/day) x {Absorption Factor (%/100)}
									Body Weight (kg)
   
   Daily Exposure (mg ai/day) = daily unit exposure (mg/lb ai)  x application rate (lb ai/A) x acres treated (A/day)
   
   	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, and
	Body Weight             =	Body weight determined to represent the population of interest in a risk
				assessment.

Margin of Exposure (MOE): The daily dermal dose and daily inhalation dose received by occupational handlers were compared to the appropriate point of departure (i.e., NOAEL) to assess the risk to occupational handlers for each exposure route. All MOE values 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, and
		NOAEL	 =	Dose level in a toxicity study, where no observed adverse effects occurred in the 				study.

Combined Risks:  Dermal and inhalation risks for intermediate-term exposures were combined in this assessment, since the toxicological effects for the dermal and inhalations routes were the same.  Dermal and inhalation risks were combined using the following formula:


		 Total MOE = 1/ ((1/ Dermal MOE) + (1/Inhalation MOE))                      
			
		4.1.2	Handlers Exposure and Risk

Summaries of the risks for occupational handlers 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 (LOC = 100) at some level of risk mitigation.  

Dermal
For all handler mixing, loading, and applying scenarios, the intermediate-term dermal risks do not exceed HED's level of concern with baseline attire (i.e., long-sleeve shirt, long pants, shoes, and socks) or baseline attire plus chemical resistant gloves.  With baseline attire, the dermal MOE for mixer/loaders was 250, and the MOE for applicators was 17,000.  With baseline attire plus chemical resistant gloves, the dermal MOE for mixer/loaders was 31,000 and the MOE for applicators was 51,000.  

Inhalation
The short- and intermediate-term inhalation risks to handlers do not exceed HED's level of concern at baseline (no respirator) for any of the handler scenarios.  With baseline attire (no respirator) the inhalation MOE for mixer loaders was 14,000 and the MOE for applicators was 22,000,000.  

Combined
Combined dermal and inhalation risks do not exceed HED's level of concern with baseline attire or baseline attire plus chemical resistant gloves. With baseline attire, the combined (dermal + inhalation) MOE for mixer/loaders was 240 and the MOE for applicators was 17,000.  With baseline attire plus chemical resistant gloves, the combined (dermal + inhalation) MOE was 9,500 for mixer/loaders and 51,000 for applicators.  

Table 4: Baseline and PPE Short-Term Exposure and Risk Estimates (MOE) for Occupational Application of Fluoxastrobin
                               Exposure Scenario
                             App Rate (lb ai/A)[1]
                            Acres Treated Daily[2]
                        Dermal Unit Exposure (mg/lb ai)
                     PPE-G Dermal Unit Exposure (mg/lb ai)
                      Inhalation Unit Exposure (mg/lb ai)
                            Dose Baseline Dermal[3]
                              PPE Dermal Dose[3]
                          Dose Baseline Inhalation[4]
                            MOE Baseline Dermal[5]
                               MOE PPE Dermal[5]
                          MOE Baseline Inhalation[5]
                           Combined Baseline MOE[6]
                              Combined PPE MOE[6]














                                 Mixer/Loader
    Mixing and Loading Liquid Formulation for Groundboom Application (PHED)
                                     0.16
                                      80
                                      2.9
                                     0.023
                                    0.0012
                                     0.012
                                    0.00010
                                   0.0002194
                                      250
                                    31,000
                                    14,000
                                      240
                                     9,500
                                  Applicator
                         Groundboom Application (PHED)
                                     0.16
                                      80
                                     0.041
                                     0.014
                                    0.00074
                                   0.000172
                                   0.0000588
                                  0.000000135
                                    17,000
                                    51,000
                                  22,000,000
                                    17,000
                                    51,000
1 Application rate is based on maximum values found in proposed label (EPA Reg. 66330-65).
2 Area treated is based on the area that can be reasonably treated in a single day based on the application method (standard EPA/OPP/HED values)
3 Daily Dermal Dose (mg/kg/day) = (Unit Exposure x Application rate x Area treated x Dermal Absorption Factor) 2.3% / 70 kg.
4 Daily Inhalation Dose (mg/kg/day) = (Unit Exposure x Application rate x Area treated x inhalation absorption factor 100%) / 70 kg.
5 Short- and Intermediate-Term MOE = NOAEL (3 mg/kg/day) / Daily Dose.  The LOC is 100.
6 Combined MOE = 1/(1/Dermal MOE + 1/Inhalation MOE)






	4.2 	Postapplication Exposure

		4.2.1	Data and Assumptions for Post-application Exposure Scenarios	

There is the possibility for agricultural workers to have post-application dermal exposure to fluoxastrobin following its proposed agricultural crop uses.  Therefore, occupational intermediate-term dermal post-application risks were assessed.

There were no chemical-specific DFR data to assess post-application risks to workers while performing tasks related to crops treated with fluoxastrobin.  Occupational post-application exposures and risks were assessed using HED's default assumptions that 20% of the initial application is available for transfer on day 0 (i.e., 12 hours after application) and that the residue dissipates at a rate of 10% per day.

HED uses a concept known as the transfer coefficient (TC) to numerically represent the post-application exposures one would receive (generally presented as cm[2]/hour).  A TC is a measure of the residue transferred from a treated surface to a person who is doing a task or activity in a treated area.  These values are the ratio of an exposure for a given task or activity to the amount of pesticide residue on treated surfaces available for transfer.  HED has developed a series of standard transfer coefficients that are unique for a variety of job tasks or activities that are used in lieu of chemical- and scenario-specific data.  HED used Policy 003.1 Science Advisory Council for Exposure Policy Regarding Agricultural Transfer Coefficients to estimate transfer coefficients for the various tasks that post-application workers might perform on each crop grouping.    

HED assumes an 8 hour workday for post-application workers and assumes 70 kg for an adult (average adult weight) since the endpoint is not based on developmental effects.

For fluoxastrobin, the exposure durations for non-cancer post-application risk assessment were short-term and intermediate-term.  However, since there is no toxicological point of departure for short-term dermal exposures, post-application risks are presented only for intermediate-term dermal exposures. The LOC for occupational post-application risk is for MOEs of 100 (i.e., an MOE < 100 is of concern).   

Daily dermal exposures were calculated on each post-application day after application using the following equation:

DE(t) (mg/day) = (DFR(t) (ug/cm[2]) x TC (cm[2]/hr) x Hr/Day) x DA / 1,000 (ug/mg)

Where:
      DE(t)      =	Daily exposure or amount deposited on the surface of the skin at time (t) attributable for activity in a previously treated area,
	DFR(t)	=	Dislodgeable foliar residue at time "t" (ug/cm[2]),
	TC	=	Transfer Coefficient (cm[2]/hour), 
       Hr/day   =	Exposure duration meant to represent a typical workday (8 hours), and
       DA         =	Dermal absorption factor (0.023)

Where:
	Default DFR (ug/cm[2]) = AR (lb ai/A) x F x (1- D)[t] x CF1 x CF2

      	AR = Maximum application rate,
      	F = Fraction of ai retained on the foliage,
      	D = Fraction of residue that dissipates daily,
      	t = Postapplication day, 
      	CF1 = 4.54E+8 ug/lb, and
      	CF2 = 2.47E-8 A/cm[2].
   
   		4.2.2 	Agricultural Exposure and Risk

The post-application exposure associated with agricultural crops is summarized in Table 5.  Using HED default assumptions, maximum transfer coefficients, and surrogate DFR data, all scenarios resulted in MOEs greater than 100 on day 0 (12 hours after application) and, therefore, were not of concern to HED.  

Table 5: Occupational Post-application Exposure to Proposed Uses of Fluoxastrobin
                                     Crop
                  Maximum Proposed Application Rate (lb ai/A)
                                   Activity
                              Foliage Development
                                      TC
                                  (cm[2]/hr)
                             Days After Treatment
                               DFR[1] (ug/cm[2])
                            Daily Dose (mg/kg/d)[2]
                                    MOE[3]
Squash/Cucumber Crop Subgroup 9B (Chayote; Chinese waxgourd; Cucumber; Gherkin; Gourd, edible; Pumpkin; Squash, summer; and Squash, winter)
                                     0.16
                      Irrigation, scouting, hand weeding
                                     Full
                                     1500
                                       0
                                   0.3588416
                                    0.0014
                                     2,100

                                     0.16
                    Hand Harvest, leaf pulling hand pruning
                                      Low
                                     2500
                                       0
                                   0.3588416
                                    0.0024
                                     1,300

                                     0.16
                 Irrigation, scouting, thinning, hand weeding
                                      Low
                                      500
                                       0
                                   0.3588416
                                    0.00047
                                     6,400
1 Default DFR (ug/cm[2]) = application rate (lb ai/A) x (1- daily dissipation rate) [t] x 4.54E8 ug/lb x 2.47E-8 A/cm[2] x 20% DFR after initial treatment.
2 Daily Dermal Dose = [DFR (ug/cm[2]) x TC x 0.001 mg/ug x 8 hrs/day x DA] x (body weight (70 kg)).
3 MOE = NOAEL/Daily Dose   (Adult Dermal NOAEL = 100 mg/kg/day).

Restricted Entry Interval:  The restricted entry interval (REI) is based on the acute toxicity of fluoxastrobin technical material.  Fluoxastrobin is classified as Toxicity Category III by the dermal route and for eye irritation potential and Toxicity Category IV for skin irritation potential.  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.  Therefore, the 12-hour REI that appears on the proposed label is adequate.
5.0	RESIDENTIAL EXPOSURE

Fluoxastrobin is registered for use in residential settings on turfgrass for use by residential handlers.  Risks for fluoxastrobin application to turf was previously assessed and did not result in risks of concern (K. Rury D371251, 3/4/2010). Therefore, a revised assessment for residential handlers was not required.  Residential handler combined dermal + inhalation risks resulted in MOEs that ranged from 3,200 to 520,000.  Post-application incidental oral risks to children resulted in an MOE of 1,600 for object-to-mouth exposure, 120,000 for ingestion of treated soil, and MOEs that ranged from 400 to 850 for hand-to-mouth exposure.  Adult dermal post-application risks resulted in MOEs that ranged from 1,100 to 16,000 from contact with treated turf, and the risk from child dermal contact with treated turf resulted in an MOE of 670.  
6.0	RESIDENTIAL BYSTANDER POST APPLICATION & SPRAY DRIFT

Based on the Agency's current practices, a quantitative post-application inhalation exposure assessment was not performed for fluoxastrobin at this time.  However, volatilization of pesticides may be a potential source of post-application inhalation exposure to individuals nearby to pesticide applications.  The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009.  The Agency received the SAP's final report on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html) and is in the process of evaluating the SAP report.  The Agency may, as appropriate, develop policies and procedures to identify the need for and, subsequently, the way to incorporate post-application inhalation exposure into the Agency's risk assessments.  If new policies or procedures are put into place, the Agency may revisit the need for a quantitative post-application inhalation exposure assessment for fluoxastrobin.

Spray Drift
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 pyraflufen-ethyl.  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.  
