UNITED ST AT ES ENVIRONMENT AL PROTECTION AGENCY

MEMORANDUM Date : January 20 , 20 1 1 SUBJECT: Fluoxastrobin : Occupational and Residential Exposure Assessment

agricultural uses of fluoxastrobin on (Chayote; Chinese waxgourd; Cucumber; Gherkin; Gourd, edible; Pumpkin; Squash, summer; and Squash, winter) PC Code: 028869 Decision No.: 433137 Petition No.: 0F7726 Risk Assessment Type: Single Chemical TXR No.: NA MRID No.: NA FROM: Kristin Rury

Risk Assessment Health Effects Division (7509P) THROUGH: Barry O’Keefe, Senior Biologist Risk Assessment Branch 3 Health Effects TO: Nancy Tsaur Risk Assessment Branch 3 Health Effects Division (7509P) The Registration Division (RD) requested that occupational exposure and risk assessment for new cucumber
. Note: This memorandum was reviewed by the Exposure Science Advisory Committee (ExpoSAC) on January 20,

Page 1 of 14 UNITED ST AT ES ENVIRONMENT AL PROTECTION AGENCY

WASHINGTON, D.C. 20460 OFFICE OF CHEMICAL SAFETY AND

POLLUTION PREVENTION

Occupational and Residential Exposure Assessment agricultural uses of fluoxastrobin on Squash and Cucumber Crop Subgroup 9B (Chayote; Chinese waxgourd; Cucumber; Gherkin; Gourd, edible; Pumpkin; Squash, summer; and Squash, winter)
. DP Barcode: 380848 Registration No.: 6 6330
- 64, Regulatory Action: Section 3 Single Chemical Case No.: NA

CAS No.: 193740
- 76
- 0 40 CFR: 180.609 Kristin Rury , Biologist isk Assessment Branch 3 Health Effects Division (7509P) Barry O’Keefe, Senior Biologist Risk Assessment Branch 3 Health Effects Division (7509P) Nancy Tsaur , Risk Assessor Risk Assessment Branch 3 Health Effects Division (7509P) Registration Division (RD) requested that the Health Effects Division (HED) conduct an exposure and risk assessment for new proposed uses of fluoxastrobin Note: This memorandum was reviewed by the Exposure Science Advisory January 20, 2011
. CHEMICAL SAFETY AND POLLUTION PREVENTION

Occupational and Residential Exposure Assessment for proposed Cucumber Crop Subgroup 9B (Chayote; Chinese waxgourd; Cucumber; Gherkin; Gourd, edible; Pumpkin;

(HED) conduct an fluoxastrobin on squash and Note: This memorandum was reviewed by the Exposure Science AdvisoryPage 2 of 14

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® 480 SC fungicide, DISARMTM 480 SC Fungicide , and Fluoxastrobin 480 SC Fungicide Seed Treatment, produced b y Arys ta LifeScience North America, LLC (Ary sta) . In this memorandum, the name fluoxastrobin will be used for the ai in this product. Proposed Use Profile : Broadcast f

oliar applications of fluoxastrobin may be applied to squash and cucumber crop subgroup 9B at a maximum application rate of 0.1 6 lb ai/A for both foliar and soil
- borne diseases . For all of crop subgroup 9B , h andlers may appl y 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 day s between applications. Exposure Profile : There is a potential for short
- and intermediate
- term occupational exposure to fluoxastrobin during m ixing, 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, onl y intermediate
- term dermal risks as well as short
- and intermediate
- term inhalation risks were assessed. The e stimated dermal and inhalation exposures were compared to the oral No Observ ed Adverse Effect Level (NOAEL ) of 3.0 mg/kg/day

from a 90 day

subchronic feeding dog study in which dose
- related reduction s 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 Observ ed 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;Page 3 of 14

therefore , cancer risk s w ere 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 appl yi ng 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 inter

mediate
- 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 w as 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 51,0 00 for applicators. Agricultural P ost - Application: Based on HED's current practices, a quantitative occupational post
- application inhalation exposure assessment was not performed for fluoxastrobi n at this time. However, there are multiple potential so urces 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 i nhalation exposure assessment for fluoxastrobin
. Intermediate
- term d ermal post
- application exposures and risks to occupational workers were estimated using standard values established b y 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 exceedPage 4 of 14

HED ’s level of concern
. The restricted entry

interval (REI) is currentl y based on the acute toxicity of fluoxastrobin technical material . Fluoxastrobin is classified as Toxicity Category I II b y 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 REIthat appears on the proposed label is adequate for protection of the expose d 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 currentl y registered on fluoxastrobin labels. 2.0 HAZARD CHARACTERIZATION The quality

of the toxicology

database for fluoxa strobin is good and the confidence in the hazard and dose
- response assessments is high. The toxicity database for fluoxa strobin 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 i s adequate, there are no residual uncertainti es for pre
- and/or postnatal toxicity , and the doses chosen as quantitative risk estimates are adeq

uately protective for infants and children. Additional ly , 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 examine d the entire toxicity database of fluoxastrobin; the database of this chemical does not show clear evidence of biologicall y relevant effects on the immune sy stem that relate to this chemical. The overall weight of evidence suggests that this chemical does not directly target the immune sy stem. 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 (UF DB ) is not needed to account for lack of this study
.Page 5 of 14

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 100 x 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. Fluoxastro bin is a moderate eye irritant (Toxicity

Category I II), 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 Ac ute oral
- rat 45865612 LD 50 >2000 mg/kg III 870.1200 Ac ute dermal
- rat 45865613 LD 50 >2000 mg/kg III 870.1300 Ac ute inhalation
- rat 45865618 LC 50 = 4.9 mg/L IV 870.2400 Ac ute eye irritation
- rabbit 45865620 mo derate irritant III 870.2500 Ac ute 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 li ver (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 inhalati on 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 fluo xastrobin are shown in Table 2
.Page 6 of 14

Table 2 : Summary of Toxicological Doses & Endpoints for Fluoxastrobin for Use in Occupational Risk Assessments Exposure Scenario Point of Departure Uncertainty/FQPA S afety F actors 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% UF A = 10X

UF H = 10X FQPA SF = 1X LOC for MOE = 100 90 D ay S ubchronic D og LOAEL = M/F 24.8/24.2 mg/kg/day (800 ppm) based on dose
- related reductions in net body

w eight 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% UF A = 10X

UF H = 10 X FQPA SF = 1 X LOC for MOE = 100 90 D ay S ubchronic D og 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. UF A = extrapolation from animal to human ( intra
- species ). UF H = 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 T able 3 provides a summary of the proposed uses of f luoxastrobin
.Page 7 of 14 Table 3: Use Profile for Fluoxastrobin f or use on Squash and Cucumber Crop Product

Information Application Method of Application Maxim um

Single Application Rate (lb ai/A) Maxim um

Number of Applications (oz) Retreatment

Interval (RTI) Maxim um

Seasonal Application Rate Squash/Cucumber Crop Subgroup 9B (Chayote; Chinese waxgourd; Cucumber; Gherkin; Gourd, edible; Pumpkin; Squash, summer; and Squash, winter) EVITO® 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 info rmation provided on proposed labels. The quantitative exposure/risk assessment for occupational handlers is based on the following exposure scenarios: Mixer/L oaders : 1. Mixing/loading liquid concentrate to support groundboom applications , and Applicators : 2. Applying spray s 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 no t submitted to the Agency in support of this Section 3 application. Itis 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 N o. 7 , January 1999)
. Mitigation Approaches: The baseline clothing level for occupational exposure scenarios is generall y an individual wearing long pants, a long
- sleeved shirt, shoes, socks, no chemical
- resistant gloves, and noPage 8 of 14

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 trac tor cabs, closed mixing/loading s ystems, and water
soluble packets. Occupational handler exposure assessments were completed b y HED using baseline clothing attire, and baseline clothing attire plus gloves. Area Treated: Based on HED ExpoSAC SOP N o. 9.1, the area treated in a day was assumed to be 8 0 acres for mixing, loading and applyingfluoxastrobin with groundboom equipment to crop subgroup 9B
. Application Rate: Broadcast f

oliar applications of fluoxastrobin may be applied at a maximum application rate of 0.1 6 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 dose s , since the selected toxicological endpoints are not based on a developmental effect
. Absorption Factor s : 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 nearl y 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 absorp tion 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:Page 9 of 14 Daily Exposure (mg ai/day) = Unit Exposure ( μ g ai/lb ai handled) x Application Rate (lbs ai/) x Daily Amount Handled (lbs/day) x Conversion Factor (mg/1,000 μg) 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 e xposure value (μg 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 logic al unit treatment such as acres (A/day). Daily Dose: Dail y dose (inhalation or dermal) was calculated b y normalizing the daily dermal or inhalation exposure value by body weight and accounting for dermal and i nhalation 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 w eight determined to represent the population of interest in a risk a ssessment. Margin of Exposure (MOE): The dail y dermal dose and dail y inhalation dose received b y occupational handlers w ere 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 = N O AEL (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.Page 10 of 14

Combined Risks: Dermal and inhalation risks for intermediate
- term exposures were combined in this assess ment, 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 a s 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 appl yi ng 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 1 7,000. Wi th 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 basel ine (no respirator) for any of the handler scenarios. With baseline attire (no respirator) the inhalation MOE for mixer loaders was 14 , 0 00 and the MOE for applicators was 22 , 0 00,000. 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 , 5 00 for mixer/loaders and 51 ,000 for applicators.Page 11 of 14 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

Bas e line 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 EP A/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)Page 12 of 14

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 fo llowing 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 numericall y represent the post
application exposures one would receive (generally presented as cm2 /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 Ad visory 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 onl y for intermediate
- term dermal exposures. The LOC for o ccupational 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) (μg/cm2 ) x TC (cm2/hr) x Hr/Day) x DA / 1,000 (μg/mg) Where: DE(t) = Daily exposure or amount deposited on the surface of the skin at time (t) attributable for activi ty in a previously treated area, DFR(t) = Dislodgeable foliar residue at time “t” (μg/cm 2 ), TC = Transfer Coefficient (cm 2 /hour), Hr/day = Exposure duration meant to repres ent a typical workday (8 hours), and DA = Dermal absorption factor (0.023)Page 13 of 14

Where: Default DFR (μg/cm2 ) = 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 μg/lb , and CF2 = 2.47E
- 8 A/cm2

. 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- a pplication Exposure to Proposed Uses of Fluoxastrobin Crop Maximum

Proposed Application Rate (lb ai/A) Activity Foliage Development TC

(cm2 /hr) Days

After Treatment DFR 1

(ug/cm2 ) Daily Dose

(m g/k g/d) 2 MOE 3 Squash/Cucu mber 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 0.002 4 1,300

0.16 Irrigation,

scouting, thinning, hand weeding Low 500 0 0.3588416 0.00047 6,400
1 Default DFR (μg/cm2 ) = application rate (lb ai/A) x (1
- daily dissipation rate) t x 4.54E8 μg/lb x 2.47E
- 8 A/cm2 x 20% DFR after initial treatment. 2 Daily Dermal Dose = [DFR (μg/cm2 ) x T C x 0.001 mg/μg 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: Th e 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 Cate gory 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 REIthat app ears on the proposed label is adequate. 5 .0 RESIDENTIAL EXPOSUREPage 14 of 14

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 ob ject
- 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 an d, 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 asse ssment for fluoxastrobin. Spray Drift Spray drift is alway s 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 exp osure from the ground application method employed for py raflufen
- 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 m anagement 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 b y the Spray Drift Task Force, a m embership of U.S. pesticide registrants, and is developing a policy on how to appropriatel y apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied b y air, orchard airblast, and ground hydraulic methods. After the poli cy 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.