### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES



### Date: April 15

, 2010

MEMORANDUM

SUBJECT: Fluoxastrobin. Human Health Risk Assessment for Proposed Uses on Sweet Corn, Field Corn/Sweet Corn Grown for Seed, and Wheat; Revised Tolerances on

Peanut and Refined Peanut Oil Based on a Peanut Processing Study; and Label Revision Allowing Homeowner Residentia l Application to Turf Grasses.

PC Code: 028869 DP Barcodes: 366179

Decision No.: 411400 Registration No.: 66330-64

Petition Nos.: 9F7567, 3F6556 Regulatory Action: Section 3 Registration Risk Assessment Type: Single Chemical/Aggregate Case No.: NA

TXR No.: NA CAS No.: 361377-29-9

MRID No.: NA 40 CFR: 180.609



### FROM: Nancy Dodd, Risk Assessor Meheret Negussie, Chemist Whang Phang, Toxicologist Barry O’Keefe, Biologist Kristin Rury, Biologist

Risk Assessment Branch III Health Effects Division (7509P)

THROUGH : Paula Deschamp, Branch Chief

Risk Assessment Branch III Health Effects Division (7509P)

TO: Tony Kish/John Bazuin, Risk Management Team #22 Fungicide Branch Registration Division (7505P)

In PP#9F7567, Arysta LifeScience North America, L.L.C. (Arysta) requested the establishment

of new tolerances for combined resi dues of the fungicide fluoxastrobin ( 1E )-[2-[[6-(2- chlorophenoxy)-5-fluoro-4-pyrimidinyl] oxy]phenyl](5,6- dihydro-1,4,2-dioxazin-3- yl)methanone O -methyloxime and its Z -isomer (1 Z )-[2-[[6-(2-chlorophenoxy)-5-fluoro-4- pyrimidinyl]oxy]phenyl](5,6-dihydro -1,4,2-dioxazin-3-yl)methanone O -methyloxime in/on the following raw agricultural commodities (RACs):

Page 1 of 64

### Wheat, grain................................................................0.09 ppm Wheat, bran...................................................................0.2 ppm Wheat, forage................................................................7.0 ppm Wheat, hay .....................................................................17 ppm Wheat, straw ..................................................................11 ppm Aspirated grain fractions................................................15 ppm Sweet corn (kernels plus cobs with husks removed) ..0.02 ppm Sweet corn, forage .........................................................13 ppm Sweet corn, stover..........................................................10 ppm Meat byproducts (cattle, goat, horse, sheep).................0.2 ppm

Under PP#3F6556, Arysta submitted a peanut processing study to resolve a condition of registration. All other resi due chemistry deficiencies for PP#3F6556 on peanuts (DP#289106, W. Wassell, 1/25/05) have now been reso lved (DP#334234, A. Acierto, 10/30/08 and DP#’s 364445 and 367049, M. Negussie, 1/20/10).

Arysta has also proposed the removal of the rest riction preventing homeowner application to turf grasses on the current fluoxastrobin turf la bel (DisarmTM G Fungicide; EPA Reg. No. 66330- 380), thereby allowing homeowner residential application to turf grasses. The current label

contains the statement “Not for homeowner use. May be applied to residential turf by a certified pest control operator.”

The most recent human health risk assessment was conducted for uses on field corn, soybean, and the low-growing berry subgroup 13-07G (DP#’s 356982 and 357473, Nancy Dodd, 8/13/09). The hazard characterization and toxicity endpoints for risk assessment were reported in a 2005 risk assessment (DP#292422, S. Winfield, 1/24/05). Since then, no new toxicology data have

been submitted. The hazard characterization and toxicity endpoints for risk assessment remain unchanged since the 2005 risk assessment. The details of the hazard ch aracterization and the rationale for toxicity endpoint selection will not be repeated in this risk assessment. However,

the salient features will be summarized for th ese two topics and the FQPA safety factor.

A summary of the findings and an assessment of human risk resulting from the proposed and registered uses of fluoxastrobin are provided in this document and its attachments. The residue chemistry data submitted in support of this pe tition were reviewed by Meheret Negussie, who also conducted the dietary assessment. The occu pational/residential assessment for food uses on sweet corn, field corn/sweet corn grown for s eed, and wheat was performed by Barry O’Keefe. The occupational/residential assessment for non- food use on turf was conducted by Kristin Rury. The toxicology evaluation was pe rformed by Whang Phang. The drinking water assessment was conducted by Rochelle Bohaty. The risk assessment was conducted by Nancy Dodd.

Recommendations for Tolerances

Pending submission of revised Sections B and F, th ere are no residue chemis try issues that would preclude granting conditional regist ration for the requested uses of fluoxastrobin on sweet corn

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### and wheat or establishment of the following tole rances for combined residues of fluoxastrobin

and its Z -isomer:

Corn, sweet, kernel plus cob with husks removed......0.01 ppm Corn, sweet, forage ........................................................13 ppm Corn, sweet, stover.........................................................10 ppm Wheat, grain................................................................0.09 ppm Wheat, bran.................................................................0.15 ppm Wheat, forage................................................................7.0 ppm Wheat hay ......................................................................17 ppm Wheat, straw ..................................................................11 ppm Grain, aspirated grain fractions......................................60 ppm

The proposed requested uses on sweet corn and wh eat increase the livesto ck dietary burden and necessitate increasing certain esta blished tolerances for combined residues of fluoxastrobin, its

Z

-isomer, and its phenoxy-hydroxypyrimidine metabolite, 6-(2-chlorophenoxy)-5-fluoro-4- pyrimidinol, in livestock commodities as follows: Cattle, meat byproducts ..............................................0.20 ppm Goat, meat byproducts ................................................0.20 ppm Horse, meat byproducts ............................................. 0.20 ppm Sheep, meat byproducts ..............................................0.20 ppm

The processing study data submitted in response to DP# 289106 (PP#3F6556) necessitates an

increase in the established tolerances for combined residues of fluoxastrobin and its Z -isomer in peanut commodities as follows:

Peanut..........................................................................0.02 ppm Peanut, refined oil .......................................................0.06 ppm

Note: In accordance with HED’s Interim Guidance on Tolerance Expressions (S. Knizner, 5/27/09), the tolerance expressions for fluoxa strobin were revised under 40 CFR §180.609 as

follow:

Under 40 CFR §180.609(a)(1): “T olerances are established fo r residues of fluoxastrobin, including is metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only fluoxastrobin (1 E )-[2-[[6-(2-chlorophenoxy)-5-fluor o-4-pyrimidinyl]oxy]phenyl](5,6- dihydro-1,4,2-dioxazin- 3-yl)methanone O -methyloxime and its Z -isomer, (1 Z )-[2-[[6-(2- chlorophenoxy)-5-fluoro-4-pyrimidinyl ]oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-3- yl)methanone O -methyloxime, calculated as the stoichio metric equivalent of fluoxastrobin.”

Under 40 CFR §180.609(a)(2): “T olerances are established fo r residues of fluoxastrobin, including is metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only fluoxastrobin, (1 E )-[2-[[6-(2-chlorophenoxy)-5-fluor o-4-pyrimidinyl]oxy]phenyl](5,6- dihydro-1,4,2-dioxazin- 3-yl)methanone O -methyloxime, its Z -isomer, (1 Z )-[2-[[6-(2-

Page 3 of 64

### chlorophenoxy)-5-fluoro-4-pyrimidinyl ]oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-3- yl)methanone O -methyloxime, and its phenoxy-hydroxypyrimidine, 6-(2-chlorophenoxy)-5- fluoro-4-pyrimidinol, calculated as the stoi chiometric equivalent of fluoxastrobin.”

Under 40 CFR §180.609(d): “Tolerances are esta blished for the indirect or inadvertent residues of fluoxastrobin, including is metabolite s and degradates, in or on the commodities in the table below, when present therein as a result of the application of fluoxastrobin to the growing crops listed in paragraph (a)(1) of this section. Compliance with the tolerance levels specified below is to be determin ed by measuring only fluoxastrobin, (1 E )-[2-[[6-(2- chlorophenoxy)-5-fluoro-4-pyrimidinyl ]oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-3- yl)methanone O -methyloxime and its Z -isomer, (1 Z )-[2-[[6-(2-chlorophenoxy)-5-fluoro-4- pyrimidinyl]oxy]phenyl](5,6-dihydro -1,4,2-dioxazin-3-yl)methanone O -methyloxime,

calculated as the stoichiometric equivalent of fluoxastrobin.”

Revisions to the Proposed Tolerances and Rationale for Differences in Proposed and

Recommended Tolerances:

Table 1. Tolerance Summary for Fluoxastrobin

Tolerance (ppm) Commodity

Established Proposed Recommended Comments; Correct Commodity Definition

40 CFR §180.609(a)(1)

Sweet corn K+CWHR

-- 0.02 0.01 Corn, sweet, kernel plus cob with

husks removed

Sweet corn, forage

-- 13 13 Corn, sweet, forage

Sweet corn, stover

-- 10 10 Corn, sweet, stover

Wheat, grain

-- 0.09 0.09

Wheat, bran

-- 0.2 0.15

Wheat, forage

-- 7.0 7.0

Wheat, hay

-- 17 17

Wheat, straw

-- 11 11

Aspirated grain fractions

-- 15 60 Grain, aspirated grain fractions

Meat byproducts (cattle, goat, horse, and sheep) -- 0.2 Remove Tolerances for meat byproducts must be proposed as indicated below under 40 CFR §180.609(a)(2)

Peanut 0.010

-- 0.02 The established tolerance must be

increased due to over-tolerance residues in peanut nutmeat in the submitted processing study.

Peanut, refined oil 0.030

-- 0.06 The established tolerance must be

increased due to an increase in the highest average field trial (HAFT) for peanut nutmeats.

40 CFR §180.609(a)(2)

Cattle, meat bypro ducts 0.10 0.20

Goat, meat byproducts 0.10 0.20

Horse, meat byproducts 0.10 0.20

Sheep, meat byproducts 0.10 0.2

0.20



### Page 4 of 64Table 1. Tolerance Summary for Fluoxastrobin

Tolerance (ppm) Commodity

Established Proposed Recommended Comments; Correct Commodity Definition

40 CFR §180.609(a)

Grain, cereal, forage, fodder, and straw, group

16. 0.10 0.10 Grain, cereal, forage, fodder, and straw, group 16, except corn and

wheat.



### As shown in the above table, some of the propos ed commodity terms had to be revised to agree with the Agency’s Food and Feed Commodity Vocabulary.

HED recommends that the proposed tolerances for corn, sweet, kernel plus cob with husks

removed of 0.02 ppm be reduced to 0.01 ppm based on the highest observed residues in sweet corn crop field trials and the limit of qua ntitation (LOQ) of th e method of 0.01 ppm for

combined residues of fluoxastrobin and its Z -isomer.

HED recommends that the proposed tolerance for wheat, bran be reduced from 0.2 ppm to 0.15 ppm and the proposed tolerance for g rain, aspirated grain fractions (AGF) be increased from 15 ppm to 60 ppm. The wheat processing study in dicates that residues of fluoxastrobin may concentrate in wheat bran (1.3x) and AGF (518x). Based on these concentration factors and the highest average field trial (HAF T) residue of 0.11 ppm for wheat grain from the submitted wheat field trials, the tolerance levels should be 0.15 ppm for wheat, bran and 60 ppm for g rain, aspirated grain fractions . According to the Residue Chemistry Test Guidelines (OPPTS 860.1500: Crop Field Trials), if the pesticide is used on more than one crop, the crop with the highest residues in the aspirated grain fractions (in this case, wheat) will be used to establish the

tolerance.

HED recommends that the estab lished tolerance of 0.010 ppm for peanut be increased to 0.02 ppm since over-tolerance residues of 0.02 pp m were found in peanut nutmeat reflecting application at 1x the proposed use ra te in the submitted processing study.

HED recommends that the estab lished tolerance of 0.030 ppm for peanut, refined oil be increased to 0.06 ppm. HED has considered the discrepancy betw een the processing factors for oil in the two peanut processing studies (8x fo r refined oil in the original study, and 0.5x for crude and refined oil in the current study), and concluded that the maximum theoretical concentration factor (MTCF) of 2.8x should continue to be used in establishing a tolerance for residues in peanut, refined oil. Based on the HAFT residue of 0.02 ppm in the current processing study and the MTCF of 2.8x for peanut oil (O PPTS 860.1520, Table 3), the expected residues in peanut, refined oil would be 0.06 ppm.

Page 5 of 64

### Table of Contents

1.0 Executive Summary .......................................................................................................... 8

2.0 Ingredient Profile ............................................................................................................ 13 2.1 Summary of Proposed Uses.................................................................................. 14

2.2 Structure and Nomenclature ................................................................................. 17 2.3 Physical and Chemical Properties......................................................................... 17

3.0 Hazard Characterization/Assessment ........................................................................... 18 3.1 Hazard and Dose-Response Characterization....................................................... 18 3.1.1 Database Summary ................................................................................... 18 3.1.1.1. Mode of action, metabolis m, toxicokinetic data.......................... 18 3.1.1.2. Sufficiency of studies/data........................................................... 19 3.1.2 Toxicological Effects................................................................................ 19 3.2 FQPA Safety Factor for Infants and Children ...................................................... 21 3.3 Level of Concern for Margin of Exposure............................................................ 22 3.4 Recommendation for Aggregate Exposure Risk Assessments ............................. 22 3.5 Classification of Carcinogenic Potential............................................................... 22 3.6 Summary of Toxicological Doses an d Endpoints for Risk Assessment............... 22 3.7 Endocrine disruption............................................................................................. 25

4.0 Dietary Exposure/Risk Characterization ..................................................................... 26 4.1 Pesticide Metabolism and Environmental Degradation........................................ 27 4.1.1 Metabolism in Primary Crops................................................................... 27 4.1.2 Metabolism in Rotational Crops ............................................................... 27

4.1.3 Metabolism in Livestock........................................................................... 27 4.1.4 Analytical Methodology ........................................................................... 27 4.1.5 Environmental Degradation..................................................................... 28 4.1.6 Comparative Metabolic Profile................................................................. 28 4.1.7 Toxicity Profile of Major Metabolites and Degradates ............................ 29

4.1.8 Pesticide Metabolites and De gradates of Concern.................................... 30 4.1.9 Drinking Water Residue Profile................................................................ 31

4.1.10 Food Residue Profile............................................................................... 32

4.1.11 International Residue Limits................................................................... 35 4.2 Dietary Exposure and Risk ................................................................................... 35 4.2.1 Acute Dietary Exposure/Risk ................................................................... 35 4.2.2 Chronic Dietary Exposure/Risk ................................................................ 35 4.2.3 Cancer Dietary Risk.................................................................................. 36 4.3 Anticipated Residue and Percent Cr op Treated (%CT) Information.................... 36

5.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................ 37 5.1 Residential Handler Exposure............................................................................... 37 5.2 Residential Postapplication Exposure................................................................... 39

5.2.1 Home Uses................................................................................................ 39

5.2.2 Recreational Uses...................................................................................... 43 5.3 Spray Drift ............................................................................................................ 43

6.0 Aggregate Risk Assessments and Risk Characterization ............................................ 44 6.1 Acute Aggregate Risk........................................................................................... 44

Page 6 of 64

### 6.2 Short-Term and Intermediate-Term Aggregate Risk............................................ 44 6.3 Long-Term Aggregate Risk .................................................................................. 45

6.4 Cancer Risk........................................................................................................... 45

7.0 Cumulative Risk Characterization/Assessment ........................................................... 45

8.0 Occupational Exposure/Risk Pathway .......................................................................... 46

8.1 Short- and Intermedia te-Term Handler Risk ....................................................... 46

8.2 Short- and Intermediate-Term Postapplication Exposure/Risk ........................... 51

9.0 Data Needs and Label Requirements ............................................................................ 54 9.1 Toxicology ............................................................................................................ 54 9.2 Residue Chemistry................................................................................................ 55 9.3 Occupational and Residential Exposure ............................................................... 56

References

............................................................................................................................... ..... 56 Appendix A: Toxicology Assessment ....................................................................................... 57 A.1 Toxicology Data Requirements ................................................................................ 57 A.2 Toxicity Profiles........................................................................................................ 58 Appendix B: Metabolism Assessment ...................................................................................... 62 Appendix C: Physical and Chemical Properties ..................................................................... 63 Appendix D: Review of Human Research ............................................................................... 64

Page 7 of 64

### 1.0 Executive Summary

Background: Fluoxastrobin controls fungal diseases by interfering w ith mitochondrial respiration in plant-pathogenic fungi, thus inhibi ting spore germination and mycelial growth. It belongs to the strobilurin cl ass of fungicides (Group 11), al so termed methoxyacrylates.

Fluoxastrobin is the accepted common name for the pesticidally active E -isomer of [2-[[6-(2- chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy]phe nyl](5,6-dihydro-1,4,2-di oxazin-3-yl)methanone

O -methyloxime. The Z -isomer of fluoxastrobin is typically present at much lower levels ( E:Z ratio of approximately 90:10).

Use Profile: Arysta proposed use of fluoxastrobin on wheat and corn (field, seed, and sweet). (Note: The Section B/label must be revised to indicate use on fi eld corn/sweet corn grown for

seed rather than on seed corn since no tolerances exist for pop corn.)

The FLUOXASTROBIN 480 SC Fungicide label (E PA Registration No. 66330-64; 4 lb ai/gal suspension concentrate (SC) formulation) is the master label which will serve as the basis for

three different sub-labels: EVITOTM 480 SC Fungicide for agricultural uses; DISARMTM 480 SC Fungicide for turf uses; and FLUOXASTROBI N 480 SC Fungicide Seed Treatment. The current action on turf is a request ed revision of the use directions on the registered turf label, DISARMTM G Fungicide (EPA Reg. No. 66330-380), a granular formulation containing 0.25%

fluoxastrobin.

For uses on wheat and corn, postemergence broadcas t foliar applications can be applied using ground, aerial, or chemigation equipment. For fi eld corn/sweet corn grown for seed, two foliar applications can be made at the maximum rate of 0.18 lb ai/A/applicat ion for a total seasonal application rate of 0.36 lb ai/A, with a preharvest interval (PH I) of 30 days. For sweet corn, four foliar applications can be made at a maxi mum rate of 0.12 lb ai/A/application for a total seasonal application rate of 0.48 lb ai/A, with a 7-day PHI. Fo r wheat, two foliar applications can be made at a maximum rate of 0.12 lb ai/A/application for a tota l seasonal application rate of 0.24 lb ai/A, with PHIs of 7 days for forage and hay, and 40 days for grain and straw. The label indicates that an adjuvant may be used on sweet corn, and a crop oil concentrate (1% v/v) may

be used on wheat. The restricted entry interval (R EI) is 12 hours.

For the registered use on peanuts, four broadcas t foliar applications of EVITOTM 480 SC can be made at the rate of 0.18 lb ai/A/application fo r a maximum seasonal appl ication rate of 0.72 lb ai/A, with a14-day PHI. The applications can be made with ground or aerial equipment.

Arysta has also proposed the removal of the rest riction preventing homeowner application to turf grasses on the registered fluoxa strobin turf label (DisarmTM G Fungicide, a 0.25% granular formulation; EPA Reg. No. 66330-380), thereby allo wing homeowner resident ial application to turf grasses. The current label contains the statement “Not for homeowner use. May be applied to residential turf by a certifie d pest control operator.” Di sarmTM G Fungicide is currently registered for use on turf (including sod farms, golf courses, lawns, and landscape areas around residential, institutional, public, commercial, and industrial buildings, park s, recreational areas and athletic fields) via broadcast application or spot treatment for control of turf fungal diseases.

Page 8 of 64

### Fluoxastrobin may be applied to ryegrass, bentgrass, bluegrass, fescue and other turf grasses at a rate of 0.5 lb ai per acre using a push spreader or a hand held, hand cr anked belly-grinder (or similar). Up to four applications may be made per year at a maximum seasonal application rate of 2 lb ai per acre. Fluoxastrobin can be safely applied before seeding, after seeding, at seedling germination, and to prevent funga l diseases in established turf. Optimum application timing for control of seedling diseases is just pr ior to, during, or after seeding.

Human Health Risk Assessment:

Toxicity/Hazard: The toxicology database provides suffici ent information to determine whether fluoxastrobin poses a human health hazard. The only data deficiency that exists is the requirement for additional information on the mouse subchronic immunotoxicity study (for potential upgrade).

Fluoxastrobin shows low acute toxici ty via the oral, dermal, and inha lation routes of exposure; is a moderate eye irritant; and is neither a dermal irritant nor a sensitizer. Following repeated administration, fluoxastrobin has mild or low toxi city in all tested sp ecies other than the dog which displayed adverse liver toxi city at considerably lower do ses than those noted for other species. As the most sensitive species, the eff ects observed in the dog were used as endpoints in the risk assessment. In both the 90-day and one-y ear oral feeding dog studies, the liver appeared to be the target organ; other target organs include the kidney (dog, mouse and rat), and the adrenal glands (rat; the effects were not considered endocrine-related).

In the available toxicity studies on fluoxastrobin, there was no estrogen, androgen, and/or thyroid mediated toxicity. The findings of increased in cidences in uterine ad enocarcinoma and thyroid

follicular cell adenoma in the rat chronic toxici ty/carcinogenicity study were determined to be unrelated to treatment. These observations, wh ich were found within random occurrence in this strain of rats, are not treatment -related and, therefore, are not indicative of possible endocrine disruption.

In the rat and rabbit developmental toxicity studies and the two-ge neration reproduction rat study, there was no increased suscepti bility to prenatal or postnat al exposure to fluoxastrobin and no effects on reproduction. Furthermore, fluoxastrobi n is not acutely neurotoxic in rats up to a single high dose of 2000 mg/kg/day, nor did fluoxastrobin show neurotoxic effects different from background levels seen in the control study fo llowing repeated dosing in the rat subchronic neurotoxicity study. Results of genotoxicity te sting were negative and there were no treatmentrelated carcinogenicity fi ndings in adequately performed carcinoge nicity studies in rats and mice. Therefore, fluoxastrobin is cla ssified under the March 2005 Cancer Guidelines as “not likely to be carcinogenic to humans.”

The RAB3 fluoxastrobin team has determined th at the1996 Food Quality Protection Act (FQPA) safety factor of 10X for protec tion of infants and children shoul d be removed for all potential exposure scenarios to fluoxastrobin because 1) the toxicity database is adequate to characterize any potential for prenatal or postn atal risk for infants and childr en; 2) there is no indication of increased susceptibility to pr e- and/or post-natal toxicity; 3) there is no indication of

Page 9 of 64

### neurotoxicity; and 4) the exposur e databases are complete or ar e estimated based on data that reasonably account for potential exposures.

No quantitative hazard estimate was selected for the short-term dermal exposure scenario based on lack of systemic or dermal toxicity in the 28-day dermal toxicity study in the rat and the absence of developmental or reproduction t oxicity findings. The adverse liver findings (cholestasis) in the 90-day subchronic dog study were used to set endpoints for the intermediate-term dermal, the short- and intermed iate-term inhalation, as well as the short- and intermediate-term incidental oral exposure scenar ios. The adverse liver findings (cholestasis) in the chronic toxicity dog study were used for setting the quantitative hazard estimate for the long-term dermal and inhalation, as well as the chronic dietary exposure scenarios (although long-term dermal and inhalation exposures are no t expected based on the proposed uses). An acute quantitative hazard estimate was not establishe d because an adverse effect attributable to a single exposure was not identified from the av ailable database (although acute exposure is expected).

Dietary Exposure (food/drinking water):

Residues of Concern : Residues in plants are primarily surface residues. For both tolerance enforcement and dietary risk assessment, residues of concern in/on plants (primary and rotational crops) are fluoxastrobin and its Z -isomer, and the residues of c oncern in/on treated livestock commodities are fluoxastrobin, its Z -isomer, and its phenoxy-hydroxypyrimidine metabolite [6- (2-chlorophenoxy)-5-fluoro-4-pyri midinol]. The residues of c oncern in drinking water are

fluoxastrobin and its Z -isomer. Fluoxastrobin is moderately mobile and persistent in terrestrial and aquatic environments.

Acute Dietary Exposure/Risk : There was no indication of an a dverse effect attributable to a single dose. An acute reference dose (aRfD) was not established.

Chronic Dietary Exposure/Risk : A conservative dietary exposu re assessment was performed for fluoxastrobin. The assumptions of this dietary assessment included tolerance level residues and 100% crop treated (CT). Based on processing studi es, the processing factors for tomato puree, potato chips, dried pota to (granules/flakes), and potato fl our were reduced to 1. Separate tolerances were set for peanut oi l, wheat bran and tomato paste; therefore, the processing factors

for these commodities were set at 1. For a ll other processed commodities, DEEM version 7.81 default processing factors were assumed. The estimated drinki ng water concentration (EDWC) value for chronic exposure, the 1-in-10 year annual mean value of 33 ppb, was directly incorporated into the dietary a ssessment. The results of the chronic dietary (food and drinking water) analysis are less than 100% of the chro nic Population Adjusted Dose (cPAD), which is below the Agency’s level of concern for the general U.S. population and all population subgroups. The dietary exposure for food and drinking water is estimated to be 19% of the cPAD for the general U.S. population and 42% of the cPAD for children 1-2 yrs old, the population subgroup with the highest estimated chronic dietary exposure to fluoxastrobin.

Cancer Dietary Risk : The Cancer Assessment Review Co mmittee (CARC) concluded that fluoxastrobin is “not likely to be carcinogenic to humans ;” therefore, an estimate of exposure for

Page 10 of 64

### calculation of cancer risk was not performed.

Residential Exposure:

Residential Handler Exposure : Because of the proposed label amendment to allow homeowner residential application to turf, the use on turf results in resi dential handler exposure from loading and applying granular fluoxastrobi n. 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. Short-term inhalation risks were not of concern to HED. Intermediate-term dermal, inhalation, and combined (intermediate-term derm al + intermediate-term inhalation) MOEs were not of concern to HED (i.e., MOE ≥ 100 

### ).

Residential Postapplication Exposure : For existing uses on register ed labels, there is potential for exposure to homeowners in residential settings from entering areas previously treated with fluoxastrobin, such as lawns where children might play, or golf courses that could lead to exposures for adults. The expansion of use to the residential handler does not alter risk assessments previously completed for resident ial postapplication scenarios. The MOEs for residential postapplication exposure to fluoxast robin are all above 100, and therefore, do not

exceed HED's level of concern.

Aggregate Risk:

Acute Aggregate Risk : Acute exposures were not consid ered because an adverse effect attributable to a single dose was not identified.

Short-Term and Intermediate-Term Aggregate Risk : There is potential s hort- and intermediateterm exposure to fluoxastrobin via the dietary (food and drinking water) pathway (which is considered background exposure) and residentia l pathway (which is considered primary exposure). For adults, these pathways lead to exposure via the oral (background), and dermal and inhalation (primary) routes. For children, th ese pathways lead to exposure via the oral (background), and incidental oral and dermal (p rimary) routes. All MO Es are greater than 100, which indicates that exposure and risk do not exceed HED’s level of concern.

Long-Term Aggregate Risk : There is potential chronic expo sure via the dietary (food and drinking water) pathway, but not through the residen tial pathway. Refer to Chronic Dietary Exposure/Risk

.

Cancer Risk : Fluoxastrobin is classified as “not likely to be carcinogenic to humans;” therefore, an aggregate cancer assessment was not conducted.

Occupational Exposure/Risk:

Short- and Intermediate-Term Handler Risk : Fluoxastrobin can be applied to sweet corn and wheat using groundboom, aerial, and chemigation equi pment. Handler exposure is expected to

be short- or intermediate-term based on information provided on the proposed labels.

Page 11 of 64

### Combined intermediate-term dermal plus in termediate-term inhalation risks do not exceed HED’s level of concern since MOEs are greater than 100 with baseline attire (i.e., long-sleeve shirt, long pants, shoes, and socks) except fo r the following scenarios which require chemical resistant gloves in additi on to baseline clothing:

• 

### mixing/loading liquid concentrat es to support aerial applica tions to sweet corn, field corn/sweet corn grown for seed, and wheat; and

• 

### mixing/loading liquid concentrat es to support chemigation a pplications to sweet corn, field corn/sweet corn grown for seed, and wheat.

The combined intermediate-term dermal plus intermediate-term inhalation risks are not of concern to HED (i.e., MOEs ≥ 100) for pilots using enclosed cockpits and wearing baseline

attire.

Short- and Intermediate-Term Postapplication Exposure/Risk :

Inhalation: Based on the Agency's current practices, a quantitative postapplication inhalation exposure assessment was not performed for fluoxa strobin primarily because it has a very low

vapor pressure.

Dermal: There is the possibility for agricultural workers to have postapplication dermal

exposure to fluoxastrobin 

### following its proposed agricultural crop uses. Therefore, occupational intermediate-term dermal postapplication risks we re assessed. All scenar ios resulted in MOEs greater than 100 on day 0 (12 hours after application); therefore, risks do not exceed HED’s level

of concern.

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

.

As a part of every pesticide risk assessment , OPP considers a large variety of consumer subgroups according to well-esta blished procedures. In line with OPP policy, HED estimates risks to population subgroups fr om pesticide exposures that ar e based on patterns of that subgroup’s food and water consumption, and activ ities in and around the home that involve pesticide use in a residential se tting. Extensive data on food consumption patterns are compiled by the USDA under the Continuing Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all registered fo od uses of a pesticide. These data are analyzed and categorized by subgroups based on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to assess di etary exposure to smaller, specialized subgroups and exposure assessments are performed when c onditions or circumstances warrant. Whenever appropriate, non-dietary exposures based on home use of pesticide products and associated risks for adult applicators and for children (three to less than six years old), youths, and adults entering or playing on treated areas posta pplication are evaluated. Further considerations are currently in development as OPP has committed resources and expertise to the development of specialized

Page 12 of 64

### software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary patte rns among specific subgroups.

Review of Human Research: This risk assessment relies in pa rt on data from studies in which adult human subjects were intent ionally exposed to a pesticide or other chemical. These studies (listed in Appendix D) have been determined to require a review of th eir ethical conduct, and

have received that review.

Additional Data Needs: Refer to Section 9.0.

2.0 Ingredient Profile

Fluoxastrobin is a strobilurin- class fungicide that controls foliar fungal diseases and soilborne/seedling fungal diseases

. It works by interrupting m itochondrial respiration, thus inhibiting spore germination and mycelial growth.

Fluoxastrobin is the accepted common name for the pesticidally active E -isomer of [2-[[6-(2- chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy]phe nyl](5,6-dihydro-1,4,2-di oxazin-3-yl)methanone

O -methyloxime. The Z -isomer of fluoxastrobin is typically present at much lower levels ( E:Z ratio of approximately 90:10). Additionally, the Z -isomer of fluoxastrobin is considered to be a metabolite (photo-degradate) of fluoxastrobin.

The FLUOXASTROBIN 480 SC Fungicide label (E PA Registration No. 66330-64; 4 lb ai/gal suspension concentrate (SC) formulation) is the master label which will serve as the basis for

three different sub-labels: EVITOTM 480 SC Fungicide for agricultural uses; DISARMTM 480 SC Fungicide for turf uses; and FLUOXASTROBI N 480 SC Fungicide Seed Treatment. The current action on turf is a request ed revision of the use directions on the registered turf label, DISARMTM G Fungicide (EPA Reg. No. 66330-380), a granular formulation containing 0.25%

fluoxastrobin.

Arysta proposes use of fluoxastrobin on wheat an d corn (field, seed, a nd sweet). The Section

B/label must be revised to indicate use on field corn/sweet corn grown for seed rather than on seed corn since no tolerances exist for pop corn.

For the proposed agricultural uses on sweet co rn, field corn/sweet co rn grown for seed, and wheat, fluoxastrobin is formulated as a solubl e concentrate (SC) formulation, EVITOTM 480 SC Fungicide (EPA Registration No. 66330-64), containing 40.3% fl uoxastrobin and 59.7% inerts, and containing 4 lbs fluoxastrobin per gallon. Po stemergence broadcast foliar applications can be applied using ground, aerial, or chemigation equipment. For fi eld corn/sweet corn grown for seed, two foliar applications can be made at th e maximum rate of 0.18 lb ai/A/application for a total seasonal application rate of 0.36 lb ai/A, with a preharvest interval (PHI) of 30 days. For sweet corn, four foliar applicati ons can be made at a maximum rate of 0.12 lb ai/A/application for a total seasonal application rate of 0.48 lb ai/A, with a 7-day PHI. For wheat, two foliar applications can be made at a maximum rate of 0.12 lb ai/A/application for a total seasonal application rate of 0.24 lb ai/A, with PHIs of 7 days for forage and hay, and 40 days for grain

Page 13 of 64

### and straw. The label indicates that an adjuvant may be used on sweet corn, and a crop oil concentrate (1% v/v) may be used on wheat. Th e restricted entry inte rval (REI) is 12 hours.

For the registered use on peanuts, four broa dcast foliar applications of EVITOTM 480 SC Fungicide can be made at the rate of 0.18 lb ai /A/application for a maxi mum seasonal application rate of 0.72 lb ai/A, with a14-day PHI. The a pplications can be made with ground or aerial equipment.

For the registered turf use, DISARMTM G F ungicide (EPA Reg. No. 66330-380) is applied a maximum of 4 times per season, at a maximum app lication rate of 0.5 lb ai/A/application with a minimum 14-day application interval and a maxi mum seasonal application rate of 2.0 lb ai/A.

Fluoxastrobin may be applied to turf (including sod farms, golf courses, lawns, and landscape areas around residential, instit utional, public, commercial, an d industrial buildings, parks,

recreational areas and athletic fi elds) via broadcast application or spot treatment for control of turf fungal diseases.

Fluoxastrobin may be applied to ryegrass, bentgrass, bluegrass, fescue and other turf grasses at a rate of 0.5 lb ai per acre using a push spreader or a hand held, hand cr anked belly-grinder (or similar). Up to four applications may be made per year at a maximum seasonal application rate of 2 lb ai per acre. Fluoxastrobin can be safely applied before seeding, after seeding, at seedling germination, and to prevent funga l diseases in established turf. Optimum application timing for control of seedling diseases is ju st prior to, during, or after seed ing. The label specifies use of the shortest specified application interval and/or the higher specifi ed rate when prolonged disease

conditions exist.

Registered agricultural crops are peanut, tubero us and corm vegetable subgroup 1C, leaf petiole vegetables subgroup 4B, fruiting vegetables gr oup 8, and turf (DP#292422, S. Winfield, 1/24/05) and field corn, soybeans, and the low-gr owing berry subgroup 13-07G (DP#’s 356982 and 357473, N. Dodd, 8/13/09).

2.1 Summary of Proposed Uses

The proposed use directions for sweet corn, field co rn/sweet corn grown for seed, wheat, and turf grasses, along with the registered use pattern for peanut (obtained from the current label for the 4 lb ai/gal SC formulation, acceptance da te 4/24/09) are presented in Table 2.1.

Page 14 of 64Table 2.1. Summary of Directions for Use of Fluoxastrobin.

Applic. Timing, Type, and Equip. Formulation 1
[EPA Reg. No.] Applic.

Rate (lb ai/A) Max.

No. Applic.

per Season Max.

Seasonal Applic.

Rate (lb ai/A) PHI (days) Use Directions and Limitations

Field Corn 2 and Field Corn/Sweet Corn Grown for Seed

Broadcast, Foliar, Ground, aerial, or chemigation 4 lb ai/gal SC [66330-64] 0.063-

0.18 2 0.36 30 Applications are to begin preventatively and continue as needed on a minimum 7-day retreatment interval (RTI). An adjuvant may be used to increase

coverage.

Sweet Corn

Broadcast, Foliar, Ground, aerial, or chemigation 4 lb ai/gal

SC [66330-64] 0.063-

0.12 4 0.48 7 Applications are to begin preventatively and continue as needed on a minimum 14-day RTI. An adjuvant may be used to increase coverage.

Wheat

Broadcast, Foliar, Ground, aerial, or chemigation 4 lb ai/gal

SC [66330-64] 0.063-

0.12 2 0.24 7 (forage and hay)

40 (grain and

straw) Applications are to begin preventatively and continue as needed on a 14- to 21-day RTI. Applications may begin at Feekes 5 (Zadoks 31) and continue up to Feekes 10.5 (Zadoks 59); application after Feekes 10.5 is prohibited. A crop oil concentrate (COC) may be added at 1% to enhance efficacy.

Peanut

Broadcast, Foliar,

Ground or

aerial 4 lb ai/gal

SC [66330-64] 0.18 lb

ai/A 4 0.72

(including any seed

treatment use) 14 Applications are to begin preventatively and continue as needed on a minimum 14-day

RTI.

Turf Grasses (Bentgrass, Bluegras s, Fescue, Ryegrass, and Others) 3

Broadcast, Foliar, Ground (Push spreader or a hand-held,

hand-cranked belly-grinder 0.25% G [66330-380] 0.5 4 2 14 Use in the establishment of turfgrass from seed or in overseeding of dormant turfgrass.

1 SC = Suspension Concentrate; G = Granular.

2 Field corn is already registered



### . 3 Arysta has proposed removal of the restriction preventing homeowner application on the current label, thereby

allowing homeowner residential application.



### The proposed use directions for sweet corn and wheat include the following resistance management restriction: make no more than two sequential app lications of the product before alternating to a fungicide with a different m ode of action for at least one application.

Page 15 of 64

### The use directions submitted in Section B do not include application spray volumes or specifications for application via chemigation. The registered labe l recommends a minimum spray volume of 10 gal/A for ground equipment and 5 gal/A for aerial equipment. The registered label states that chemigation applications ar e to be made through sp rinkler-type irrigation systems only.

The use directions submitted in Section B do not include rotational crop restrictions. The following crop restrictions appear on the registered label: 0-day plant-back interval (PBI) for any crop listed on the label; 30-day PBI for root vegetables (e.g., carrot, radish, sugar beet, and turnips), bulb vegetables (e.g., onion and garl ic), leafy greens subgr oup (e.g., lettuce and spinach), Brassica vegetables (e.g., broccoli, cauliflower, cabbage, and mustard greens), alfalfa, cotton, legume vegetables (dry and succulent peas and beans), cereal grains, and forage grasses; and a 12-month PBI for all other crops.

Conclusions . The submitted use directions are adequate to allow evaluation of the residue data relative to the proposed use. The submitted field trial data for sweet corn and wheat reflect the maximum proposed use rates, the minimum RTIs, a nd the proposed PHIs except as noted below.

In the submitted field trials, samples of sweet corn forage and K+CWHR were harvested at a ~7- day PHI following four applicati ons; however, PHIs for sweet corn stover were 23-35 days. The proposed use directions should be revised to specify a minimum PHI for corn stover of 23 days.

In the submitted field trials, wheat forage was harvested ~7 days after a single application of fluoxastrobin, while hay, grain, a nd straw were harvested after tw o applications. The proposed

use directions should be revise d to include the following statement: Make no more than one application prior to ha rvest of wheat forage.

Spray adjuvants were not used in the sweet corn field trials, and a noni onic surfactant (NIS) was used in only 8 of 25 wheat field trials. The wheat field trial data indicated that use of an NIS resulted in higher residues in wheat forage. HE D has concluded that spra y adjuvant use must be prohibited on product labels when the field tria ls did not include adj uvants (see minutes of 4/16/08 Chemistry Science Advisory Council (Che mSAC) meeting); in additional field trials which HED is requesting, HED is requesting us e of an adjuvant (sweet corn) or crop oil concentrate (wheat).

Page 16 of 64

### 2.2 Structure and Nomenclature

Fluoxastrobin is described in Table 2.2.

Table 2.2. Fluoxastrobin Nomenclature

Chemical Structure

Cl

O

N N F

O O O

N

N
O

CH 3

Empirical Formula C 21 H 16 ClFN 4 O 5

Common name Fluoxastrobin Note: This name was originally approved for a mixture of the E - and Z -isomers (CAS # 193740-76-0) in April 2002. The definition of fluoxastrobin was changed

to mean the E -isomer only in January 2003. This change was made based upon a request by the petitioner.

Company experimental name HEC 5725

IUPAC name ( E)-{2-[6-(2-chlorophenoxy)-5-fluoropyrimidin-4-yloxy]phenyl}(5,6-dihydro1,4,2-dioxazin-3-yl)methanone O -methyloxime

CAS name (1 E)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy]phenyl](5,6-dihydro1,4,2-dioxazin-3-yl)methanone O -methyloxime

CAS Registry Number 361377-29-9

End-use product/EP FLUOXASTROGBIN 480 SC Fungicide (EPA Reg. No. 66330-64)/ EVITOTM 480 SC Fungicide (EPA Reg. No. 66330-64); DISARMTM G Fungicide (EPA Reg. No. 66330-380)

Chemical Class Strobilurin, methoxyacrylates

Known Impurities of

Concern Fluoxastrobin Z -isomer



### 2.3 Physical and Chemical Properties

Fluoxastrobin has a low vapor pressure (5.63 x 10 -10 

### Pa at 20 °C); therefore, inhalation via chemical vaporization is unlikely. The physicoche mical properties of fluoxastrobin are tabulated in Appendix C.

Page 17 of 64

### 3.0 Hazard Characterization/Assessment

References:

HED/RAB3 fluoxastrobin hazard meetings, October and November 2004.

Fluoxastrobin: Human Health Risk Assessment for Proposed Uses on Peanuts, Tuberous and Corm Vegetables (Subgroup 1C), Leaf Petiole Vegetables (Subgroup 4B), Fruiting Vegetables (Group 8), Turf, and as a Seed Treatment on Potato (See d Piece), Peanut and Turf , DP#292422, S. Winfield, 01/24/05.



### A detailed hazard characterization for fluoxastrobi n is presented in a previous risk assessment (DP#292422, S. Winfield, 1/24/05). The available toxi city studies are listed in Appendix A. The salient features of toxicology for risk assessment are presented here.

3.1 Hazard and Dose-Response Characterization

3.1.1 Database Summary

3.1.1.1 Mode of action, metabo lism, toxicokinetic data

Fluoxastrobin is considered a novel strobilurin analog (other strobilurin fungicides include azoxystrobin, dimoxystrobin, kresoxim-methyl, metominostrobin, orysastrobin, picoxystrobin, pyraclostrobin, and trifloxystrobin).

The pesticidal biochemical mode of action of st robilurins consists of interaction with the ubiquinone binding site of the m itochondrial bc1 complex (complex III) in fungal cells, thereby preventing the oxidation of ubihydroquinone and the transfer of electrons to cytochrome c. Interrupting the electron transpor t chain in this way prevents oxidative phosphorylation, thus causing a severe reduction in the availability of ATP, the main energy currency of the cell. The shortage of energy has a very wide range of biochemical consequences, such as the breakdown of essential membrane potentials and concentra tion gradients and the inhibition of nucleic acid and protein biosynthesis. Fungal spore germin ation, mycelial growth and the development of

infection structures are thus prevented.

Following an 8-hour dermal application in a male monkey, absorption was negligible (1.16% preliminary, 2.16% main). The normalized abso rption value for the main study was 2.31%.

Absorption, distribution, and metabolism were fu lly characterized in several rat metabolism studies using three 14 

### C-radiolabeled rings in fluoxastro bin. Fluoxastrobin was extensively

metabolized.

Page 18 of 64

### 3.1.1.2 Sufficiency of studies/data

The submitted studies are of good quality and pr ovide sufficient information to determine whether fluoxastrobin poses a human health hazard. The only data deficiency that exists at this time is the requirement for additional information on the mouse subchronic immunotoxicity study (for potential upgrade).

To address the issue of immunotoxicity data requ irements as presented in the 40 CFR Part 158, RAB 3 has examined the entire toxicity database of fluoxastrobin; the database of this chemical

shows no indication that this chem ical directly targets the imm une system. An immunotoxicity study in mouse is available; the results of this study show no apparent decrease on B-cell activated, T-cell mediated IgM response to sh eep red blood cells (SRBC) at doses as high as 2383 mg/kg/day. However, this stud y has many deficiencies includi ng 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 a dditional factor for data base uncertainty (UF DB 

### ) is

not needed to account for lack of this study. However, the regist rant should upgrade the study to meet the data requirement.

Based on the available toxicity da tabase and the Agency's current practices, the inhalation risk

for fluoxastrobin was assessed usi ng an oral toxicity study. The Agency sought expert advice and input on issues related to th is route to route extrapolation approach (i.e. the use of oral toxicity studies for inhalation risk assessment) from its Fede ral Insecticide, Fungicide, and

Rodenticide Act Scientific Advi sory Panel (SAP) in December 2009. The Agency received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SA P/meetings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report and may, as appropriate, re-examine and develop new policies and procedures for conducting inhalati on risk assessments, in cluding route to route extrapolation of toxicity data. If any new policies or procedures are developed, the Agency may

revisit the need for an inhalation toxicity study for fluoxastro bin and/or a re-examination of the inhalation toxicity risk assessment.

3.1.2 Toxicological Effects

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 ir ritant (Toxicity Category III), but is neither a dermal irritant

nor a skin sensitizer. The acute toxic ity profile can be found in Appendix A.2.

Fluoxastrobin seems to have a mild or low toxicity following repeated administration in all tested species other than the dog. In both the 90-day and one-year oral feedi ng dog studies, there was liver toxicity in the form of cholestasis as evidenced by hepatocytomegaly and cytoplasmic granular changes associated with increased li ver weight and increased serum liver alkaline phospatase (ALP). In addition, several phase I and phase II liver drug metabolizing enzymes were induced. Other toxicity in dogs included body weight loss or redu ced gain, decreased food efficiency, and effects on kidneys including increased relative weight in females and

Page 19 of 64

### degeneration of proximal tubular epithelium in males. The no observed adverse effect level (NOAEL) of 1.5 mg/kg/day in the one year dog study was used for setting the chronic RfD.

The liver also seemed to be a target organ in ot her studies but the toxicolo gical relevance of liver findings in species other than the dog is questi onable. For instance, among the changes were increased liver weight in the mouse and rat with hypertrophy a nd cytoplasmic changes in the mouse. However, there were no increases in any of the seru m liver enzymes including ALP.

In the 90-day oral toxicity study in rats, the urinary system in males was a target organ as evidenced by increased kidney weight and hist opathology findings in kidneys, urinary bladder, and urethra including the presence of calculi in the ur ethra and kidneys. In another rat study, there were markedly increased urinary pHs in males in addition to increased urinary calcium

excretion in the form of calcium oxalate crystals. Kidney change s were also seen in a 90-day mouse feeding study with increased kidney we ights and tubular hypert rophy in females. Following 90-day administration in dogs, ther e was degeneration of the proximal tubular epithelium in males.

The adrenal glands seem to be another target organ in males of the 90-day rat study where

vacuolation was seen in the zona fasciculate of the adrenal corte x. In another 30-day rat feeding study, adrenal cortical cytomegaly with fine va cuolization was seen in all high dose males and the responses were comparable between th e groups treated with the pure fluoxastrobin E - or 2:1

E

/ Z

-isomers. The adrenal changes are not lik ely to be endocrine related effects.

In the rat and rabbit developmental toxicity studies and the two-ge neration reproduction rat study, there was no increased suscepti bility to prenatal or postnat al exposure to fluoxastrobin and no effects on reproduction.

Fluoxastrobin is not acutely neur otoxic in rats up to a single high dose of 2000 mg/kg/day or by repeated dietary feeding in the rat subchronic neurotoxicity screening study where the top dose was nearly half the limit dose of 1000 mg/kg/day. Other studies in rats including the subchronic, chronic toxicity/carcino genicity, two-generation reproduction, and developmental toxicity were

tested to or above the limit dose with no indi cation of clinical signs, histopathology or other signs of toxicity that could be attributed to neurotoxicity. Also, in both the 90-day and one-year dog studies, neurologic examinations, including mental status/beh avior, gait char acteristics, postural status and reactions, and spinal/cranial reflexes, were carried out and were found within

normal limits.

Fluoxastrobin is not immunotoxic based on repeated dosing studies in rats and mice. In the 90- day oral toxicity rat study, th ere was no difference between the control and treated animals in spleen cell count, macrophage act ivities after PMA stimulation and plaque-forming cell assay after challenge with sheep erythroc ytes. Slight decreases were not ed in IgG concentration in the high dose males but not females. An unaccep table subchronic immunotoxicity study in mice found 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.

Fluoxastrobin and major metabolites were nega tive in a battery of genotoxicity tests.

Page 20 of 64

### The carcinogenic potential of fluoxa strobin was adequately tested in rats and mice of both sexes.

The results demonstrated a lack of treatment-relate d increase in tumor incidence in rats or mice. There was no mutagenicity concern and no structur e activity relationship aler t. It was concluded that there was no incidence of carcinogenici ty for fluoxastrobin (DP# 292422, S. Winfield, 1/24/05). No cancer risk is expected from the exposure scenarios.

3.2 FQPA Safety Factor for Infants and Children

The fluoxastrobin risk assessment team has evalua ted the quality of the toxicology and exposure

data and has determined that it is safe for infa nts and children to conti nue to reduce the FQPA safety factor to 1X. The decision is based on the following findings:

1. The adequacy of the fluoxastrobin data has been described in Section 3.1.1.2. To reiterate, the toxicity databa se for fluoxastrobin is complete for FQPA safety evaluation and toxicity endpoint and point s of departure evaluation. However, under the new rule for registration, an immunotoxicity study is requ ired. There is an immunotoxicity study; however, this study has many defi ciencies including uncertainty in dietary test material intake, and the study is classified as unaccepta ble. At this time, HED does not believe that conducting a new functional immunotoxi city study will resu lt in a lower NOAEL than the regulatory dose for risk assessmen t, and an additional factor for database uncertainty (UF DB 

### ) is not needed to account for lack of this study. However, the registrant should upgrade the study to meet the data requirement.

2. The database for evaluating in utero or postnatal susceptibility is adequate and includes developmental toxicity studies in both rats and rabbits and a tw o-generation reproduction study in the rat. The data provide no indica tion of increased susceptibility of rats or rabbits to pre- and post-na tal exposure to fluoxastrobin

3. There is no indication in the toxicity data which include acute and subchronic neurotoxicity studies that fluoxast robin is a neurotoxic chemical.

4. The exposure databases are complete or ar e estimated based on data that reasonably account for potential exposures. The diet ary food exposure assessment was performed

based on 100% CT and tolerance-level resi dues. EFED has provided conservative ground and surface water modeling estimates. The HED Residential SOPs are used to assess post-application exposure to children as well as in cidental oral exposure of children (three to less than six years old). These assessments will not underestimate the exposure and risks posed by fluoxastrobin.

Page 21 of 64

### 3.3 Level of Concern for Margin of Exposure

Target Margins of Exposure (MOEs) for risk as sessment are summarized in the table below.

Table 3.4. Summary of Levels of Concern for Risk Assessment

Route Short-Term

(1 - 30 Days) Intermediate-Term

(1 - 6 Months) Long-Term

(> 6 Months)

Occupational (Worker) Exposure*

Dermal N/A 100 100

Inhalation 100 100 100

Residential Exposure*

Dermal 100 100 N/A

Inhalation N/A 100 100

Incidental Oral 100 100 100

* 10x for intraspecies variation and 10x for interspecies extrapolation = 100x.



### 3.4 Recommendation for Aggregat e Exposure Risk Assessments

As per FQPA, 1996, when there are potential residential exposures to the pesticide, aggregate risk assessment must consider exposures from three major routes: oral, dermal and inhalation exposures. The toxicity endpoints selected for these routes of exposure may be aggregated as follows: For short-term aggregate exposure risk assessment, the oral and inhalation routes can be combined; and for intermediate- and long-term aggregate exposure risk assessments, the oral, dermal (oral equivalent) and inha lation routes can be combined because of the common toxicity endpoints (reduced body weight and liver toxicity) via these routes.

3.5 Classification of Carcinogenic Potential

Fluoxastrobin is classified as “ not likely to be carci nogenic to humans” as discussed in Section

3.1.2.

3.6 Summary of Toxicological Doses and Endpoints for Risk Assessment

The summary of toxicological doses and endpoi nts for human health risk assessment are presented below in two separate tables: 1) Di etary and Non-Occupationa l exposures in Table 3.6.1; and 2) Occupational exposures in Table 3.6.2.

Page 22 of 64Table 3.6.1. Toxicological Doses and Endpoints for Fluoxastrobin for Use in Dietary and Non-Occupational

Human Health Risk Assessments Exposure/

Scenario Point of Departure (POD) Uncertainty/FQPA Safety Factors RfD, PAD,

Level of

Concern for

Risk

Assessment Study and Toxicological Effects

Acute Dietary (General Population, including

Infants and Children) None Not applicable Not applicable There was no indication of an adverse effect attributable to a single dose. An

aRfD was not established.

Acute Dietary (Females 13- 49 years of age) None Not applicable Not applicable There was no indication of an adverse effect attributable to a single dose. An

aRfD was not established.

Chronic Dietary (All Populations) NOAEL=

1.5 mg/kg/day UF A = 10x

UF H = 10x FQPA SF= 1x Chronic RfD

= 0.015 mg/kg/day

cPAD = 0.015 mg/kg/day Chronic toxicity in the dog LOAEL = M/F:8.1/7.7 mg/kg/day based on body weight reductions and hepatocytomegaly and cytoplasmic changes associated with increased serum liver alkaline phosphatase indicative of

cholestasis.

Incidental Oral Short-Term (1- 30 days)

and

IntermediateTerm (1-6 months) NOAEL=

3.0 mg/kg/day UF A = 10x

UF H = 10x FQPA SF= 1x Residential

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).

Dermal ShortTerm (1-30 days) Not applicable None None None: There were no systemic or dermal toxicity findings in a 28-day dermal toxicity study in the rat up to the limit dose (1000 mg/kg/day) and there were no developmental or neurotoxicity concerns

raised in other studies.

Dermal

IntermediateTerm (1-6 months) NOAEL=

3.0 mg/kg/day UF A = 10x

UF H = 10x FQPA SF= 1x

Dermal absorption

rate = 2.3% Residential

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).



### Page 23 of 64Table 3.6.1. Toxicological Doses and Endpoints for Fluoxastrobin for Use in Dietary and Non-Occupational

Human Health Risk Assessments Exposure/

Scenario Point of Departure (POD) Uncertainty/FQPA Safety Factors RfD, PAD,

Level of

Concern for

Risk

Assessment Study and Toxicological Effects

Dermal Long-Term (> 6 months) NOAEL=1.5 mg/kg/day UF A = 10x

UF H = 10x FQPA SF= 1x

Dermal absorption

rate = 2.3% Residential

LOC for

MOE = 100 Chronic toxicity in the dog
LOAEL = M/F:8.1/7.7 mg/kg/day based on body weight reductions and hepatocytomegaly and cytoplasmic changes associated with increased serum liver alkaline phosphatase indicative of

cholestasis.

Inhalation

Short- Term (1-30 days) NOAEL=

3.0 mg/kg/day UF A = 10x

UF H = 10x FQPA SF= 1x Residential

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

IntermediateTerm (1-6 months) NOAEL=

3.0 mg/kg/day UF A = 10x

UF H = 10x FQPA SF= 1x Residential

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 Long-Term (> 6 months) NOAEL=1.5 mg/kg/day UF A = 10x

UF H = 10x FQPA SF= 1x Residential

LOC for

MOE = 100 Chronic toxicity in the dog LOAEL = M/F:8.1/7.7 mg/kg/day based on body weight reductions and hepatocytomegaly and cytoplasmic changes associated with increased serum liver alkaline phosphatase indicative of

cholestasis. Cancer (oral, dermal, inhalation) Classification: “Not likely to be Carcinogenic to Humans.”

Point of Departure (POD) = A data point or an estimated po int that is derived from observed dose-response data and used to mark the beginning of extrapolation to determine risk associated with lower en vironmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intra species). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level

of concern.



### Page 24 of 64Table 3.6.2 Summary of Toxicological Doses and Endpoints for Fluoxastrobin for Use in Occupational

Human Health Risk Assessments Exposure/

Scenario Point of Departure (POD) Uncertainty

Factors Level of Concern

for Risk

Assessment Study and Toxicological Effects

Dermal ShortTerm (1-30 days) Not applicable None None None: There were no systemic or dermal toxicity findings in a 28-dermal toxicity study in the rat up to the limit dose (1000 mg/kg/day) and there were no developmental or neurotoxicity concerns

raised in other studies.

Dermal

IntermediateTerm (1-6 months) NOAEL=

3.0 mg/kg/day UF A = 10x

UF H = 10x FQPA SF= 1x

Dermal absorption

rate = 2.3% Occupational 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

IntermediateTerm (1-6 months) NOAEL=

3.0 mg/kg/day UF A = 10x

UF H = 10x FQPA SF= 1x Occupational 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.”

Point of Departure (POD) = A data point or an estimated poin t that is derived from observed dose-response data and used to mark the beginning of extrapolation to determine risk associated with lower en vironmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intrasp ecies). MOE = margin of exposure. LOC = level of

concern.



### 3.7 Endocrine disruption

As required under FFDCA section 408(p), EP A has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (inc luding pesticide active and other ingredients) may have an effect in humans or wildlife si milar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two-tiered ap proach to making the statutorily required

determinations. Tier 1 consists of a battery of 11 scr eening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2

Page 25 of 64

### testing is designed to identify a ny adverse endocrine related eff ects caused by the substance, and establish a quantitative relationship betw een the dose and the E, A, or T effect.

Between October 2009 and February 2010, EPA is issuing test orders/data call-ins for the first group of 67 chemicals, which contains 58 pesticid e active ingredients and 9 inert ingredients.

This list of chemicals was selected based on th e potential for human exposure through pathways such as food and water, residen tial activity, and certain post-applic ation agricultural scenarios.

This list should not be construed as a lis t of known or likely endocrine disruptors.

Fluoxastrobin is not among the group of 58 pesticide active ingredients on th e initial list to be

screened under the EDSP. Under FFDCA sec. 408(p), the Agency must screen all pesticide chemicals. Accordingly, EPA anticipates i ssuing future EDSP orders/data call-ins for all Registration Review cases, including those for which EPA has already opened a Registration Review docket for a pestic ide active ingredient.

For further information on the status of the ED SP, the policies and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening battery, pleas e visit our website: http://www.epa.gov/endo/.

4.0 Dietary Exposure/Risk Characterization

References:

Fluoxastrobin. Petition for the Establishment of Permanen t Tolerances for Uses on Sweet Corn and Wheat. Submission of Peanut Processing Data in Response to Conditional Registration Requirements (PP#3F6556). Summary of Analytical Chemistry and Residue Data . DP#’s 364445 and 367049, M. Negussie, 1/20/10.

Fluoxastrobin: Chronic Dietary (Food and Drinking Water) Exposure Assessments for the Section 3 Registration Action Uses on Sweet Corn and Wheat (PP#9F7567) and Submission of Peanut Processing Data in Response to Conditional Registration Requirements (PP#3F6556), DP#367050, M. Negussie, 1/22/10.

Fluoxastrobin. Human Health Risk Assessment for Proposed Uses on Field Corn, Soybean, and the Low-Growing Berry Subgroup 13-07G , DP#’s 356982 and 357473, N. Dodd, 8/13/09.

Fluoxastrobin. Petitions for the Establishment of Permanen t Tolerances for New Uses on Low-Growing Berry Crop Subgroup 13-07G (PP#8F7406), Soybean and Field Corn (PP#8F7437). Summary of Analytical Chemistry and
Residue Data, DP#356953, M. Negussie, 7/8/09.

Fluoxastrobin. Supplemental Residue Data for Livestock Metabolism, Residue Analytical Methods, Storage Stability, Crop Field Trials, and Rotational Crop Field Trials, Submitted to Fulfill Conditions of Registration for Fluoxastrobin 480 SC (EPA Reg. No. 66330-64), DP#334234, A. Acierto, 10/30/08.

PP#3F6556. Fluoxastrobin. Petition for the Establishment of Perm anent Tolerances for Use on Peanuts, Tuberous and Corm Vegetables Subgroup, Leaf Petiole Vegetables Subgroup, Fruiting Vegetables Group, and Seed Treatment of Peanut and Potato, DP#’s 289106 and 289107, W. Wassell, 1/25/05.

Fluoxastrobin: Human Health Risk Assessment for Proposed Uses on Peanuts, Tuberous and Corm Vegetables (Subgroup 1C), Leaf Petiole Vegetables (Subgroup 4B), Fruiting Vegetables (Group 8), Turf, and as a Seed Treatment on Potato (Seed Piece), Peanut and Turf, DP#292422, S. Winfield, 1/24/05.



### Page 26 of 64

### 4.1 Pesticide Metabolism and Environmental Degradation

4.1.1 Metabolism in Primary Crops

The nature of the residue in sweet corn, field co rn/sweet corn grown for seed, wheat, and peanuts is adequately defined. The metabolism data on wh eat, peanuts, and tomatoes indicate that the metabolism is similar in three dissimilar crops . Based on these plant metabolism studies, HED

concludes that the residues of concern in the primary plant crops (sweet corn, field corn/sweet corn grown for seed, wheat, and peanuts) for risk assessment and tolerance setting purposes are

fluoxastrobin and its Z -isomer.

4.1.2 Metabolism in Rotational Crops

The available confined rotational crop studies on Swiss chard, turni p, and spring wheat are adequate to delineate the nature of the residue in rotated crop commodities. The studies indicate

that the metabolism of fluoxastrobin in rotational cr ops is similar to that in primary crops. The only metabolite identified in the confined rotational crop studies that was not identified in the primary crop metabolism studies was HEC5725-des -chlorophenyl-keto-diox azine. The ratio of

E : Z -isomer in fluoxastrobin identif ied in rotational crop matrices ranged from 98:2 to 74:26. Based upon the submitted studies, the residues of c oncern for rotational crops for risk assessment and tolerance setting purposes are fluoxastrobin and its Z -isomer.

The confined rotational crop st udies indicate the potential for quantifiable residues of

fluoxastrobin to occur in rotated crop commodities.

4.1.3 Metabolism in Livestock

The nature of the residue in ruminants and poultr y is adequately defined. The available data indicate that the metabolism in goats and hens is similar. Metabolism of fluoxastrobin was found to be more extensive in livestock than in pl ants, and metabolites consis ting of single rings (e.g., 2-chlorophenol and 2-cyanophenol) were observed in each of the livestock metabolism studies. Based on the submitted studies, HED concludes that the residues of concern for livestock

commodities for risk assessment and tolera nce setting purposes are fluoxastrobin, its Z -isomer, and the phenoxy-hydroxypyrimidine metabolite [6-(2 -chlorophenoxy)-5-fluoro-4-pyrimidinol].

4.1.4 Analytical Methodology

Plant commodity methods

Enforcement method: An adequate LC/MS/MS method (00604) is available for the enforcement

of tolerances for residues of fluoxastrobin and its Z -isomer in corn, wheat, and peanuts. Adequate method validation, concurrent method recoveries, independent laboratory validation data, and radiovalidation data are available. An adequate confirmatory LC/MS/MS method (00946) is also available which mon itored two mass ion transitions, m/z 459 → 427 and

459 → 188, for the determination of residues of fluoxastrobin a nd its Z-isomer in crop

commodities.

Page 27 of 64

### Data collection methods: The data collection me thods [HPLC/MS/MS method 00668, LC/MS/MS method 00604, and a method base d on method 00604 (EPL-BAS Method No. 489G317A-1)] are adequate for data collection based on acceptable method validation and concurrent method recovery data. The validated LOQs were 0.01 ppm for combined residues of

fluoxastrobin and its Z -isomer in/on all crop commodities.

Livestock commodity methods

Enforcement method: An adequate tolerance enforcement method (LC/MS/MS Method 00691, with confirmatory method 00945) is available for livestock commodities. Method 00691 and confirmatory method 00945 have been adequately validated for determination of fluoxastrobin,

its Z -isomer, and HEC 7154 in ruminant commoditi es. The method LOQs for fluoxastrobin ( E +

Z

isomers) and HEC 7154 are 0.01 ppm for each an alyte in milk, muscle, and fat and 0.02 ppm for each analyte in liver and kidney.

Multiresidue Methods

Based on the results of testing through FDA Multi-Residue Method Te st guidelines in the Pesticide Analytical Manual, Volume I ( PAM I; dated 1/94), the multiresidue methods are not adequate for enforcement of the proposed tolerances.

4.1.5 Environmental Degradation

The environmental fate data indicate that the proposed use of fluoxastrobin as a foliar spray on agricultural crops could potential ly lead to fluoxastrobin in drinking water. Although foliar interception may reduce the amount of fluoxastrobin av ailable for runoff, it is believed that this chemical could reach surface waters through spray drift, penetration of the canopy to the soil surface at application, and foliar washoff followe d by runoff. Fluoxastrobin did not seem to leach underground. It is very unlikely that any degradate/metabolite of fluoxastrobin will persist in the environment for any extended period of time to reach surface water and/or leach into ground water at any considerable amount.

4.1.6 Comparative Metabolic Profile

For metabolism studies, fluoxastrobin rings are nu mbered as ring 1 (chlorophenyl ring), ring 2 (pyrimidine ring), ring 3 (methoxyiminotolyl ring), and ring 4 (dioxazine ring).

Fluoxastrobin was extensively metabolized in th e rat as evidenced by the extensive metabolic profiles from urine, feces, and bile, and the rela tive absence of parent compound (except in the feces of rats given the high dose). The urinary me tabolites were primarily the result of cleavage between rings 2 and 3 of the parent compound. Biliary metabolites we re primarily products resulting from cleavage of rings 2, 3, and 4, a nd subsequent hydroxyla tion, methoxylation, and conjugation with glucuronic acid. HEC5725- E -des-chlorophenyl and HEC5725-des-chlorophenyl-dioxazi ne-OH were the major metabolite s in all excretion matrices.

Page 28 of 64

### Some of the rat metabolites seem to be in common with metabolites in studies from the lactating goat (e.g., HEC5725-di-OH and its dioxazine-OH, HEC5725- E -des-chlorophenyl and its derived ketone, dioxazine-OH, and glycol , in addition to seve ral dioxazine phenyl two ring metabolites) and laying hen (e.g., several glucuronide conj ugates of HEC5725- including mono- and di-OH-GA, and oxime-GA in addition to mono- and bi-ring fragments including dioxazine-oxime, 2-cyanophe nol, and salicylic acid).

Fluoxastrobin was not extensively metabolized in some primary plants but was extensively metabolized in rotational crops, as evidenced by the extensive metabolic profiles and relative absence of parent compound. The major meta bolic route of fluoxastrobin in rotated crop matrices was hydroxylation, especially at the 4-po sition of the chlorophenyl moiety to yield

HEC5725- E -4-hydroxyphenyl; conjugates of this metabolite were also observed. A second important metabolic route was cleavag e of fluoxastrobin to yield HEC5725- E -des-chlorophenyl, which was partly isomerized to the Z- isomer. Cleavage of the ether bridge between the pyrimidine and methoxyiminotolyl rings of the pa rent compound was a minor metabolic route in rotational crops. Another minor metabolic route was hydroxylati on of the parent compound in the dioxazine ring, followed by oxi dative cleavage and hydrolysis.

Fluoxastrobin was extensively metabolized in go ats and hens, as evid enced by the extensive metabolic profiles and relative absence of pare nt compound, except in goat and poultry fat where a significant portion of the resi due was identified as fluoxastrobin. Metabolites consisting of single rings (e.g., 2-chlorophenol) were observed in each of the livestock metabolism studies. One of the main metabolism pathways appear s to be cleavage of the ether group in the pyrimidine moiety to form metabolites containing ring 1 and 2 (e.g., HEC5725-phenoxy-hydroxypyrimidine) and containi ng only ring 1 (e.g., 2-chlorophenol).

4.1.7 Toxicity Profile of Major Metabolites and Degradates

All metabolites that contain the ether bridge (between the phe nyl and pyrimidinyl rings) may share similar toxicity to the parent based on their structural similarity to the parent.

Page 29 of 64

### 4.1.8 Pesticide Metabolites and Degradates of Concern

Table 4.1.8 Summary of Residues to be included in the Risk Assessment and Tolerance Expression

Matrix Residues included in Risk

Assessment Residues included in Tolerance Expression

Plants Primary and Rotational Crops Fluoxastrobin and its

Z

-isomer Fluoxastrobin and its

Z

-isomer

Livestock Ruminant and Poultry Fluoxastrobin, its Z -isomer,and its phenoxyhydroxypyrimidine

metabolite [6-(2- chlorophenoxy)-5-fluoro-4- pyrimidinol] Fluoxastrobin, its Z -isomer,and its phenoxyhydroxypyrimidine

metabolite [6-(2- chlorophenoxy)-5-fluoro-4- pyrimidinol]

Drinking Water Fluoxastrobin and its

Z

-isomer Not Applicable



### Rationale for Inclusion of Metabolites and Degradates

The metabolic profile of fluoxastrobin is extensive and comprehensive. The metabolites identified at significant levels in metabolism st udies on representative livestock, primary crops, and rotational crops were also identified in rat me tabolism studies; therefore, their potential toxic effects are assumed to have been taken into account in the toxicity stud ies. Fluoxastrobin was extensively metabolized in livestock and th e phenoxy-hydroxypyrimidine metabolite (which was identified at significant levels ) was included in the tolerance expression. The potential toxic

effects of this metabolite are assumed to have been taken into account in the toxicity studies

since it was also identified in the rat metabolism studies.

Primary Crops: Plant metabolism studies usin g wheat, peanuts, and tomatoes indicate that

fluoxastrobin and its Z -isomer are the only major residues identified (>10% TRR) with the exception of one other metabolite (HEC5725- E -4-OH-Glc-MA) which was only detected in a livestock feed item (wheat forage). The an alytical method proposed for enforcement of tolerances for residues in/on plant commodities determines combined residues of fluoxastrobin

and its Z -isomer and does not determine the analytes individually.

Rotational Crops: The petitioner has proposed 30-day plan t-back intervals and/or tolerances for residues in rotational crops based upon a 30-day pl ant-back interval. For the 30-day plant-back interval, fluoxastrobin was the major residue identified, with only a few exceptions, in Swiss chard (12-30% TRR), turnip tops (11-33% TRR), turnip roots (27-48% TRR), wheat forage (33- 49% TRR), wheat hay (33-40% TRR), and wheat straw (20-44% TRR). Fluoxastrobin was identified at varying amounts in 30- day wheat grain (0-65% TRR). The Z -isomer of fluoxastrobin was identified in Swiss chard (0-3 .1% TRR), turnip tops (0-2.3% TRR), turnip roots (2.1-2.8% TRR), wheat forage (1.2-2.8% T RR), wheat hay (0-4.3% TRR), wheat straw (0- 5.6% TRR), and wheat grain (0-1.3% TRR). No other residues were identified in all crops. The analytical method proposed for enforcement of tolerances for residues in/on plant commodities

Page 30 of 64

### determines combined residues of fluoxastrobin and its Z -isomer and does not determine the analytes individually.

Livestock: Livestock metabolism studies using lactating goats and laying hens indicate that residues of fluoxastrobin and its phenoxy-hydr oxypyrimidine metabolite [6-(2-chlorophenoxy)- 5-fluoro-4-pyrimidinol] are presen t at significant levels in all ruminant and hen tissues. The phenoxy-hydroxypyrimidine does not contain the ether bridge (between the phenyl and pyrimidinyl rings) and may be less toxic th an the fluoxastrobin. However, the phenoxyhydroxypyrimidine metabolite residue levels in ti ssues may act a surrogate for other residues (such as HEC5725-di-OH-diene- pyrimidine-OH and HEC5725-di -OH-diene) which are not determined by the proposed enforcement method for livestock commodities. The analytical method proposed for enforcement of toleran ces for residues in/on livestock commodities determines residues of fluoxastrobin, its Z -isomer, and its phenoxy-hydroxypyrimidine

metabolite. Residues of fluoxastrobin and its Z-is omer are determined as combined residues and not individually.

Water: Residues of fluoxastrobin and its Z -isomer are expected to be persistent in the environment. The two major soil metabolites (HEC5725- E -des-chlorophenyl and HEC5725- carboxylic acid) were identified in laboratory studies. Howe ver, HEC5725-carboxylic acid was

not detected in the field studies and HEC5725-E-des-chlorophenyl was detected at minor levels (<10% of applied ra dioactivity). The Z -isomer of fluoxastrobin was de tected in all of the field

studies.

4.1.9 Drinking Water Residue Profile

Reference: Drinking Water Assessment to Support Fluoxastrobin Use on Sweet Corn and Wheat, DP#366189, R. Bohaty, Ph.D., 1/13/10.



### The estimated chronic drinking water concentr ation for fluoxastrobin (33 ppb; 1-in-10 year annual mean) was calculated based on the use on tu rf (4 applications at the rate of 0.55 lb ai/A/application and a 14-day application interval).

Table 4.1.9. Summary of Estimated Surfa ce Water and Ground Wa ter Concentrations

Fluoxastrobin

Surface Water Conc., ppb a Ground Water Conc., ppb b

Acute 83 <1

Chronic (cancer) 33 <1

a From the Tier 1 First (FQPA Index Reservoir Screening Tool) model. Input parameters are based on the turf use (4 ground applications of 0.55 lb ai/A/application with a 14-day interval), which generates the highest EDWCs.

b From the Tier 1 SCI-GROW (Screenin g Concentration in Groundwater) model, also based on the turf use (4 ground applications of 0.55 lb ai/A/application with a 14-day interval), assuming a maximum use rate of 2.2 lb ai/A/year.



### Page 31 of 64

### 4.1.10 Food Residue Profile

Primary (Treated) Crops

DER References: 47754804.der.doc (Sweet corn) 47754803.der.doc (Wheat)



### Fluoxastrobin appears to have mainly foliar activ ity with only limited translocation within the plant.

Arysta has submitted field trials supporting new uses of fluoxastrobin on sweet corn and wheat.

The results from these studies are summarized below.

Table 4.1.10.1. Summary of Re sidue Data from Crop Field Trials with Fluoxastrobin.

Residue Levels (ppm) 1 Crop matrix Total Applic.

Rate (lb ai/A) PHI (days) n Min. Max. HAFT 2 Median Mean Std.

Dev.

Sweet Corn (proposed use = 0.48 lb a i/A total application rate, 7-day PHI)

Sweet corn, forage 3-8 20 0.34 5.15 4.78 2.20 2.33 1.57

Sweet corn, K+CWHR 3-8 20 <0.01 0.01 0.01 0.01 0.01 N/A

Sweet corn, stover 0.48-0.52

23-35 20 0.25 5.68 4.71 1.24 1.64 1.43

Wheat (proposed use = 0.24 lb ai/A total application rate, 7-day PHI (forage and hay) and 40-day PHI (grain and straw))

Wheat, forage 0.12-0.13 6-13 50 0.27 4.14 4.00 1.14 1.67 1.19

Wheat, hay 6-11 50 0.69 10.57 9.86 4.49 4.86 2.72

Wheat, grain 21-69 49 <0.01 0.11 0.11 0.01 0.02 0.02

Wheat, straw 0.24-0.26

21-69 50 0.18 14.55 12.26 0.81 1.79 2.91

1 Combined residues of fluoxastrobin and its Z -isomer.

2 HAFT = Highest average field trial result.



### The submitted wheat and sweet corn field trials reflect the proposed use patterns, provided the

directions for use are revise d as specified in OPPTS 860.1200. Samples were analyzed for

residues of fluoxastrobin and its Z -isomer using acceptable met hods, and the studies are supported by adequate storage stability data. Ho wever, the number and locations of the field

trials are not in accordance with OPPTS 860.1500 fo r either sweet corn or wheat. For sweet corn, two additional sweet corn field trials must be conducted in Zones 1 (1 tr ial) and 5 (1 trial). For wheat, two additional wheat field trials mu st be conducted in Zone 8. Although additional field trials are required, HED cons iders that the exposure databases are complete or are estimated based on data that reasonably account for potential exposures.

Pending revision of the proposed use patterns and submission of the outstanding field trial data, the submitted sweet corn field trial data will support the proposed tolerances of 13 ppm for forage and 10 ppm for stover, but a lower tolerance of 0.01 ppm must be proposed for

K+CWHR. The submitted wheat field trial data will support the proposed tolerances of 7.0, 17, 0.09, and 11 ppm for wheat forage, ha y, grain, and stra w, respectively.

Page 32 of 64

### Processed Food and Feed

DER References: 47588901.der.doc (Peanut) 47754802.der.doc (Wheat)

Table 4.1.10.2. Summary of Processing Factors for Fluoxastrobin.

RAC Processed Commodity Processing Factor

Meal 0.5x

Crude Oil 0.5x Peanut, nutmeat

Refined Oil 0.5x

Bran 1.3x

Flour <0.2x

Middlings <0.3x

Shorts <0.6x

Germ 0.6x Wheat, grain

Aspirated grain fractions (AGF) 518x



### The submitted processing data for peanut and wheat are adequate to fulfill data requirements. The application rates used in the study (1x the maximum registered use rate for peanut and 5x the maximum proposed use rate for wheat) were sufficient to produce det ectable residues in peanut nutmeats and wheat grain. Samples were analyzed for residues of fluoxastrobin and its Z

isomer using acceptable methods, and the wheat st udy is supported by adequate storage stability data; the available storage stability data on pean ut nutmeat are adequate and can be used to support the peanut processed commod ities due to the nature of th e raw agricultural commodity.

In the processing study, following four foliar applications of the 4 lb ai/gal SC formulation of

fluoxastrobin at a total rate of 0.72 lb ai/A (1x the maximum seasonal application rate),

combined residues of fluoxastrobin and its Z -isomer were 0.02 ppm in peanut nutmeat. Since residues of 0.02 ppm in peanut nutmeat exceed the established tolera nce for peanut of 0.010 ppm, a tolerance of 0.02 ppm mu st be proposed for peanut.

The data from the current peanut processing stud y indicate that residues of fluoxastrobin and its

Z

-isomer are unlikely to concentrate in peanut processed commodities (meal and refined oil). However, RAB3 has considered the discrepancy be tween the processing factors for oil in the two peanut processing studies (8x for refined oil in the original study, and 0.5x for crude and refined oil in the current study), and concluded that the MTCF of 2.8x should con tinue to be used in establishing a tolerance for residues in peanut, refined oil. Based on the increased HAFT of 0.02 ppm, resulting from over-tolerance residues in peanut nutmeat in the current processing study and the MTCF of 2.8x for peanut oil, expected residues in peanut, re fined oil would be 0.06 ppm; therefore, the tolerance for peanut, re fined oil must be incr eased to 0.06 ppm.

The data from the wheat processing study indica te that residues of fluoxastrobin and its Z -isomer are unlikely to concentrate in wheat flour, middli ngs, shorts, or germ, but do concentrate in AGF (518x) and concentrate sligh tly in wheat bran (1.3x).

Page 33 of 64

### Based on the HAFT for wheat grai n of 0.11 ppm and the 1.3x con centration factor for bran, expected residues in wheat bran would be 0.14 ppm, which exceeds the recommended tolerance for wheat grain of 0.09 ppm; therefore, a tolera nce for wheat bran should be established at 0.15 ppm. For AGF, based on the 0.11-ppm HAFT and the 518x concentration f actor, a tolerance of 60 ppm should be proposed.

Field Accumulation in Rotational Crops

Adequate field rotational crop data are availabl e, including a limited fi eld rotational crop study and an extensive field rotational crop study.

The limited field rotational crop study was conduc ted on the representative crops of mustard greens (leafy vegetable), turnips (root vegetable) , and wheat (cereal grain). The primary crops each received four spray applications of fluoxastrobin at ~0.18 lb ai/A, for total application rates

of ~0.72 lb ai/A. The limited field rotational cr op data, which indicated no quantifiable residues

of fluoxastrobin and its Z -isomer in mustard greens and turnip roots and tops at a 30-day plantback interval (PBI), are adequate to suppor t the proposed 30-day PB I for root and tuber vegetables, bulb vegetables , leafy vegetables, and Brassica

.

Based on the results of the limited field rotationa l crop study, the petitioner conducted extensive field rotational crop studies reflecting a 1-month plant-back interval on alfalfa, cereal grains, cotton, grass, and legume vegetables. Based on the extensive field rotational crop data, tolerances were established in 40 CFR §180.609 (d) for the indirect or inadvertent combined

residues of fluoxastrobin and its Z -isomer in/on the following rota ted crops: alfalfa forage at 0.050 ppm; alfalfa hay at 0.10 ppm; cotton gin byproducts at 0.020 ppm; forage, fodder and straw of cereal grain, group 16, at 0.10 ppm; gra ss forage at 0.10 ppm; gr ass hay at 0.50 ppm; and foliage of legume vegetable, group 7, at 0.05 pp m. The data indicated that a tolerance for residues in/on legume vegetables, crop group 6, was not needed. In addition, the following rotational crop restri ctions were included on the master label (EPA Registration No. 66330-64): “Treated areas may be replanted immediately fo llowing harvest with a ny crop listed on this label. In addition, areas may be replanted with root vegeta bles subgroup (e.g., carrot, radish, sugar beet, turnips), bulb vegetables (e.g., onion and garlic), leafy green s subgroup (e.g., lettuce, spinach), Brassica vegetables (e.g., broccoli, cauliflower , cabbage, mustard greens), alfalfa, cotton, legume vegetables (dry and succulent peas and beans), cereal grains, and forage grasses following a 30-day plant-back interv al. For all other crops, do not plant back within one year of the last field application.”

The field rotational crop data are adequate to su pport the established rota tional crop restrictions on the master label (EPA Registration No. 66330-64) a nd the indirect or inadvertent tolerances in 40 CFR §180.609 (d).

Meat, Milk, Poultry, and Eggs

The potential exists for secondary residues to occur in some livestock commodities. There are several livestock feedstuffs (sweet corn forage, stover, and cannery waste, and wheat forage, hay, straw, grain, milled byproducts, and aspirated grain fractions) associated with the proposed uses

Page 34 of 64

### on sweet corn and wheat and other livestock feedst uffs associated with re gistered uses including

field corn. The dietar y burdens were calculate d using HED’s June 2008 Table 1 Feedstuffs and guidance on constructing maximum reasonably bala nced diets (MRBD). The calculated dietary

burdens of fluoxastrobin are estimated at 6.5 and 16.6 ppm for beef a nd dairy cattle, and 0.093 and 0.090 ppm for poultry and swine, respectively.

The available ruminant feeding study is adequa te to support the proposed uses. The feeding study data and dietary burden calc ulations indicate that the establ ished tolerances for the meat byproducts of cattle, goat, horse, and sheep must be increased; the proposed tolerances of 0.20 ppm for these commodities are appropriate. The feeding study data also indicate that no changes are needed to the existing tolerances for milk, milk fat, and the fat and meat of cattle, goat, horse, and sheep.

No tolerances have been established for swin e commodities. The ruminant feeding study and dietary burden calculations indicate that no tolerances are required for swine commodities since Category 3 of 40 CFR §180.6( a)(3) applies, i.e., there is no reasonable expectation of finite

residues in swine commodities.

Based on the available poultry metabolism st udy and low dietary burden, no poultry feeding study is needed to support the proposed uses. No tolerances are needed for poultry commodities since Category 3 of 40 CFR §180.6(a)(3) applies, i.e ., there is no reasonable expectation of finite residues in poultry commodities.

4.1.11 International Residue Limits

There are currently no establis hed Codex or Canadian maximu m residue limits (MRLs) or

tolerances for fluoxastrobin on sweet corn and wheat.

4.2 Dietary Exposure and Risk

4.2.1 Acute Dietary Exposure/Risk

There was no indication of an adverse effect at tributable to a single dos e. An aRfD was not

established.

4.2.2 Chronic Dietary Exposure/Risk

A chronic dietary (food and dri nking water) exposure and risk assessment was conducted using the Dietary Exposure Evaluation Model (DEEM -FCIDTM, Version 2.03), which uses food consumption data from the U.S. Department of Agriculture’s Continuing Surveys of Food Intakes by Individuals (CSFII) from 1994-1996 and 1998. A conservative dietary exposure assessment was performed for fluoxastrobin. Th e assumptions of this dietary assessment included tolerance level residues and 100% crop tr eated (CT). Based on processing studies, the processing factors for tomato pur ee, potato chips, dry potato (gra nules/flakes), and potato flour were reduced to 1. Separate tolerances were se t for peanut oil, wheat bran and tomato paste; therefore, the processing factors for these comm odities were set at 1. For all other processed

Page 35 of 64

### commodities, DEEM version 7.81 default processing factors were assumed. The estimated drinking water concentration (EDWC) for chronic exposure, the 1-in-10 year annual mean value of 33 ppb, was incorporated directly into the di etary assessment. The results of the chronic dietary (food and drinking water) analysis are below the Agency’s level of concern for the general U.S. population and all population subgr oups. The dietary (food and drinking water) exposure is estimated at 19% of the chronic P opulation Adjusted Dose (cPAD) for the general U.S. population and 42% of the cPAD for child ren 1-2 yrs, the population subgroup with the highest estimated chronic dietary exposure to fluoxastrobin.

Table 4.2.2. Result of Chronic Di etary Exposure and Risk Estimates for

Fluoxastrobin

DEEM-FCID
Population Subgroup cPAD, mg/kg/day Exposure, mg/kg/day % cPAD

Chronic Dietary Estimates

U.S. Population 0.015 0.002772 19

All infants (<1 year old) 0.015 0.003563 24

Children 1-2 years old 0.015 0.006252 42

Children 3-5 years old 0.015 0.005411 36

Children 6-12 years old 0.015 0.003639 24

Youth 13-19 years old 0.015 0.002355 16

Adults 20-49 years old 0.015 0.002360 16

Adults 50+ years old 0.015 0.002350 16

Females 13-49 years old 0.015 0.002307 15



### 4.2.3 Cancer Dietary Risk

Fluoxastrobin is classified as “not likely to be carcinogeni c to humans;” therefore, no cancer risk is expected.

4.3 Anticipated Residue and Percent Crop Treated (%CT) Information

Tolerance level residues and 100% CT were used for all commodities included in the

assessment.

Based on experimentally derived processing factors for tomato puree, potato chips, dry potato (granules/flakes), and potato fl our, the processing factors for these commodities were 1. Separate tolerances were set for peanut oil, wheat bran, and tomato paste; therefore, the processing factors for these commodities were se t at 1. For all other processed commodities, DEEM version 7.81 default processing factors were assumed.

Page 36 of 64

### Page 37 of 64 TABLE 4.3. Processing Factors (PF) fo r Fluoxastrobin Diet ary Risk Assessment

Processed Commodity PF Source Beef, meat, dried 1.92 DEEM Default

Corn grain, sugar/high fructose corn syrup 1.5 DEEM Default

Cranberries, juice 1.1 DEEM Default

Peanut, butter 1.89 DEEM Default

Peanut, oil 1.0 Tolerance for peanut, oil accounts for processing Potato, dried and flour 1.0 Processing Study

Tomato, dried 14.3 DEEM Default

Tomato, juice 1.5 DEEM Default

Tomato, paste 1.0 Tolerance for tomato, paste accounts for processing
Tomato, puree 1.0 Processing Study

Wheat, bran 1.0 Tolerance for wheat, bran accounts for processing



### 5.0 Residential (Non-Occupational) Exposure/Risk Characterization

References:

Fluoxastrobin: Occupational and Residential Exposure Assessment for Proposed Field Uses on Sweet Corn,

Field/Sweet Corn Grown for Seed, and Wheat, DP#367052, B. O’Keefe, 2/19/10.

Fluoxastrobin. Residential Exposure/Risk Assessment for Proposed Non-food Uses by Residential Handlers on Turf

Grasses , DP#371251, K. Rury, 3/4/10.



### 5.1 Residential Handler Exposure

Because of the proposed label amendment to allow homeowner residential a pplication to turf, the use on turf results in residential handler exposur e. Residential handlers may be exposed from loading and applying granular fl uoxastrobin for spot treatment and/or broadcast control of diseases on turf. Loading/applying with a pus h spreader and loading/applying with a belly grinder were assessed. Because of the potential for application four times per year, exposure duration is expected to be shor t-term and intermediate-term. A short-term dermal endpoint was not identified; therefore, only intermediate-term dermal risks as well as short- and intermediateterm inhalation risks were assessed. The es timated dermal and inhalation exposures were compared to the oral No Observed Adverse E ffect Level (NOAEL) of 3.0 mg/kg/day from a 90- day subchronic feeding dog study. Calculation inputs and resu lts of this assessment are presented in Table 5.1.1. A combined MOE was calculated for intermediate-term dermal and intermediate-term inhalation exposures because th e endpoints and point of departures were the

same for both scenarios. Short-term inhalation ri sks were not of concern to HED. Intermediateterm dermal, inhalation, and combined (inter mediate-term dermal + intermediate-term inhalation) MOEs were not of concern to HED (i.e., MOE ≥ 100 

### ).Table 5.1.1: Exposure and Risk Estimates (MOE) for Homeowner Lawn/Garden Application with FluoxastrobinExposure ScenarioCrop orTargetAppRate (lbai/A)1AcresTreatedDaily2DermalUnitExposure(mg/lbai)3InhalationUnitExposure(ug/lb ai)4IntermediateTermBaselineDermalDose(mg/kg/day)5Short- andIntermediateTerm BaselineInhalationDose6CombinedDailyDose7MOEIntermediateTermDermal8MOE ShortandIntermediateTermInhalation9Intermediate-TermCombinedBaselineDermal+InhalationMOE10Loader/ApplicatorLoading/Applying Granulars viaPush Type Spreader (ORETF)Turf0.50.50.670.000880.00000550.000000310.0000058550,0009,500,000520,000Loading/Applying Granulars viaBelly Grinder or Similar (PHED)Turf0.50.5100.0620.0009040.0000220.000933,300140,0003,2001Application rate is based on maximum valuesfound in proposed label (EPA Reg. No. 66330-380).2Area treated is based on the area that can be reasonably treatedin a single day based on the application method (standard EPA/OPP/HED values).3Dermal Unit Exposure PHED Baseline represents long pants, long sleeved shirts, no gloves, open mixing/loading. ORETF BaselineDermal Exposure represents long pants and short sleeves.4PHED Baseline Inhalation Exposure represents no respiratory protection, open mixing/loading. ORETF Baseline Inhalation Exposure represents no respiratory protection, open mixing/loading.5Dermal Daily Dose (mg/kg/day) = (Unit Exposure (mg/lb ai) * dermal absorption (0.023) * Application rate * Area treated) / 70 kg.6.Inhalation Daily Dose (mg/kg/day)= (Inhalation unit exposure (ug/lb ai) * (1mg/1000ug)conversation*Application Rate*Area Treated)/body weight (70kg)7Combined Daily Dose= Baseline Dermal Dose + Baseline Inhalation Dose8MOE Baseline Dermal = NOAEL(3.0 mg/kg/day)/Dermal Dose9MOE Baseline Inhalation = NOAEL(3.0 mg/kg/day)/Inhalation Dose10Combined Baseline Dermal + Inhalation MOE = NOAEL / (Baseline Dermal MOE + Baseline Inhalation MOE).Page 38 of 64

### 5.2 Residential Postapplication Exposure

There is potential for exposure to homeowners in residential settings from entering areas previously treated with fluoxastrobin, such as lawns where children might play, or recreational exposures on golf courses that coul d lead to exposures for adults and youths. As a result, risk assessments have been completed for residential postapplication scenarios.

The best data and methodology currently availabl e were used in the fluoxastrobin residential assessment. Since chemical-specific data were unavailable, the Agency used the current approaches for residential assessment, many of wh ich include recent upgrades to the SOPs. For example, for the hand-to-mouth calculations for child ren (three to less than six years old), a 5% transferability factor was app lied to calculate residue levels appropriate for this exposure pathway. Overall, the Agency believes that the calculated risks represent screening level estimates. Estimates are thought to be conserva tive, even when measures of central tendency (e.g., most transfer coefficients) are used, because values that would be considered to be in the lower percentile aspect of any i nput parameter have not been used in the calculations. Maximum application rates have been used for all scen arios. Also, these risk estimates assume no dissipation of residues after day zero, and do not account for the periodic growth and cutting of the grass. Actual residues shoul d be considerably lower, and intermediate-term exposures are therefore unlikely. Further, because a short-term dermal toxicity endpoint was not identified, the intermediate-term endpoint was us ed for all dermal risk estimat es, even though the residential exposure duration is believed to be mos tly short-term based on the use pattern.

Based on the Agency's current practices, a qua ntitative postapplication inhalation exposure assessment was not performed for fluoxastrobin at this time primarily because it has a very low vapor pressure. However, volatilization of pesticides may be a potential source of postapplication inhalation exposure to individuals nearby to pestic ide applications. The Agency sought expert advice and input on is sues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rode nticide 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/SA P/meetings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report and may, as appropriate, develop policies and procedures to identify the need for and, subsequently, th e way to incorporate pos tapplication inhalation exposure into the Agency's risk assessments. If ne w policies or procedures are put into place, the Agency may revisit the need fo r a quantitative post application inhalation exposure assessment

for fluoxastrobin.

5.2.1 Home Uses

Proposed use of fluoxastrobin on turf may result in individuals of varying ages potentially being exposed from activities in areas that have been treated. Potential rout es of exposure include dermal (adults and children) and incidental oral ingestion (children [three to less than six years old] only). Since no acute haza rd has been identified, an a ssessment of episodic granular ingestion was not conducted. While it is assumed that most residential use will result in short-term (1 to 30 days) postapp lication exposures, it is also believed that intermediate-term exposures (> 30 days to 180 days) ar e possible, albeit unlikely.

Page 39 of 64

### Page 40 of 64 The highest use rate was chosen for the asse ssment (i.e., 0.5 lb ai/A). A summary of the estimated exposures and risks, along with the algo rithms used for each turf exposure scenario are presented below in Tables 5.2.1.1 through 5.2.1.4.Table 5.2.1.1.Dermal Exposure and Risk for Adults and Children from Treated Lawns (Intermediate-Term)SubgroupexposedActivityApplicationRate(lb ai/A)Fractionof aiAvailableTurf TransferrableResidue at Day “0"(μg/cm2)1DermalTransferCoefficient(cm2/hr)ExposureTime(hrs/day)DermalAbsorptionFactorBodyWeight(kg)DailyDose2(mg/kg/day)IntermediateTermMOE3AdultMowing turf40.50.050.2803,40022.3%700.00064,800AdultGolf Course Reentry0.50.050.28050042.3%700.000216,000AdultHigh Contact0.50.050.28014,50022.3%700.00271,100ChildrenHigh Contact0.50.050.2805,20022.3%150.00456701Turf Transferrable Residue (μg/cm2) = Application rate (lb ai/A) x Fraction ofai Available x 4.54E+8 μg/lb x 2.47E-8 A/cm22Daily Dose = (Turf Transferrable Residue x 1E-3 mg/μg x DermalTransfer Coefficient x Dermal Absorption Factor x Exposure Time)/Body weight3Intermediate-Term Dermal MOE = Intermediate-Term Oral NOAEL (3 mg/kg/day) /Daily Dose4Transfer Coefficient from K. Lowe (February 2009): Revised Mesotrione: Occupational and Residential Exposure/Risk Assessment for the New Use on Turf in Commercial and Residential Sites.Because this transfer coefficientis usually applied to occupational mowing of turfand golf courses, this estimate is considered extremely conservative for residential exposure estimation. Adulttransfer coefficients from contact with treated turf are short-term estimates, while intermediate-term dermal endpoints were used because of the lack ofa short-term dermal endpoint. Therefore, adultpost-application risk estimates are considered extremely conservative.Table 5.2.1.2.Oral Hand-to-mouth Exposure and Risk for Childrenfrom Treated Lawns (Short- and Intermediate-Term)Exposure DurationApplicationRate(lb ai/A)Fraction ofai AvailableTurfTransferrableResidue at Day“0" (μg/cm2)1ExposureTime(hrs/day)Extractionby salivaHand SurfaceArea(cm2/event)Frequency(events/ hr)BodyWeight(kg)Daily Dose2(mg/kg/day)MOE3Short-Term0.50.050.2820.52020150.0075400Intermediate-Term0.50.050.2820.5209.5150.003558501Turf Transferrable Residue (μg/cm2) = Application rate (lb ai/A) x Fraction of aiAvailable x 4.54E+8 μg/lb x 2.47E-8 A/cm22Daily Dose = (Turf Transferrable Residue (μg/cm2) x Extraction by Saliva x Hand Surface Area (cm2/event) x Frequency (events/hr) x 1E-3 mg/μg x ET (hrs/day)] / [Body Weight (kg)]3MOE = Oral NOAEL (3 mg/kg/day) /Daily DoseTable 5.2.1.3.Oral Object-to-mouth (Turfgrass) Exposure and Risk for Children from Treated Lawns (Short- and Intermediate-Term)Application Rate(lb ai/A)Fraction of aiAvailableGrass Residue at Day “0"(μg/cm2)1Surface Area Mouthed(cm2/day)Body Weight(kg)Daily Dose2(mg/kg/day)Short-/Intermediate-TermMOE30.50.21.125150.001916001Grass Residue (μg/cm2) = Application rate (lb ai/A) x Fraction of aiAvailable x 4.54E+8 μg/lb x 2.47E-8 A/cm22Daily Dose = [Grass residue (μg/cm2) x Surface Area Mouthed (cm2/day) x 1E-3 mg/μg] / [Body Weight (kg)]3Short- / Intermediate-Term Oral MOE = Short- / Intermediate-Term Oral NOAEL (3 mg/kg/day) /Daily DosePage 41 of 64Page 42 of 64Table 5.2.1.4. Exposure and Risk for Children from Ingestion ofSoil from Treated Lawns (Short- and Intermediate-Term)Application Rate(lb ai/A)Fraction of aiAvailableSoil Residue at Day “0"(μg/g)1Ingestion Rate(mg/day)Body Weight(kg)Daily Dose2(mg/kg/day)Short- / Intermediate-TermMOE30.513.8100150.0000251200001Soil residue (μg/g) = [Application Rate (lbs ai/A) x Fraction of ai Available x 4.54E+8 μg/lb x 2.47E-8 A/cm2x 0.67 cm3/g soil]2Daily Dose = [Soil residue (μg/g) x Ingestion rate (mg/day) x 1E-6 g/μg] / [Body Weight (kg)]3MOE = Oral NOAEL (3 mg/kg/day) /Daily Dose

### Page 43 of 64 The MOEs for residential postapplication e xposure to fluoxastrobin are all above 100, and therefore, do not exceed HED's level of concern.

HED combines risk values resulting from separa te postapplication exposure scenarios when it is likely they can occur simultaneously based on the use-pattern and the behavior associated with the exposed population. For posta pplication exposure to children, HED generally combines the dermal and incidental oral (hand to mouth) e xposures, but does not in clude additional exposure from soil ingestion, or mouthing (i.e., object-to -mouth), since the hand-to-mouth exposure is considered to be a conservative upper-bound estima te of oral postapplication exposure. For the proposed turf uses of fluoxastrobin, the total (der mal + incidental oral) postapplication MOE for

children resulted in an MO E of 370 and was not of concern to HED (MOE > 100). Table 5.2.1.5 presents a summary of the postapplication MOE estimates for adults and children.

Table 5.2.1.5. Summary of Residential Postapplicat ion Exposure and Risk Esti mates from Treated Lawns

Daily Dose 1
(mg/kg/day) MOE 2 Combined

MOE 3

Adults

Adult Residential

Contact with Treated

Turf 0.0027 1,100 N/A

Children

Child Oral Hand To

Mouth 0.00355 850

Child Contact with

Treated Turf 0.0045 670 370

1. Daily Dose = unit exposure*Applica tion Rate*Area treated)/body weight

2. MOE = NOAEL (3.0 mg/kg/day) ÷ Daily Dose

3. For children, total MOE = NOA EL (3.0 mg/kg/day) ÷ (Daily Dose child oral hand to mouth + Daily Dose child contact with treated turf).



### 5.2.2 Recreational Uses

Recreational exposures to turf ar e expected to be similar to, or in many cases less than, those

evaluated in section 5.2.1 Home Uses; therefore, a separate re creational exposure assessment was not included. Additionally, golf course e xposures and risks were already assessed.

5.3 Spray Drift

Spray drift is always a potential source of expos ure to residents nearby to spraying operations. This is particularly the case with aerial appl ication, but to a lesser ex tent, could also be a potential source of exposure from the ground application methods additionally employed for fluoxastrobin. The Agency has been working w ith the Spray Drift Task Force, EPA Regional Offices, and State Lead Agencies for pesticide re gulation and other partie s to develop the best

### Page 44 of 64 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 Sp ray Drift Task Force, a membership of U.S. pesticide registrants, and is de veloping a policy on how to appr opriately 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 appl ication types where appropriate.

It is noted that the 0.5 lb ai/acre application rate for turf was modeled to estimate postapplication residential exposure of children (three to less than six years old). As this rate is equal to or higher than many agricultural applic ation rates, this scenario is protective of any exposure of farm children via spray drift from ag ricultural fluoxastrobin applications.

6.0 Aggregate Risk Assessments and Risk Characterization

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

6.1 Acute Aggregate Risk

Acute exposures were not considered because an a dverse effect attributable to a single dose was

not identified.

6.2.1 Short-Term and Intermediate-Term Aggregate Risk

There is potential short- and in termediate-term exposure to fluoxa strobin via the dietary (which is considered background exposure) and residential (which is cons idered primary) pathways. For adults, these pathways lead to exposure via th e oral (background), and dermal and inhalation (primary) routes. For children, these pathways lead to exposure via the oral (background), and incidental oral and dermal (primary) routes. MOEs are greater than 100, which indicates that exposure and risk do not exceed HED’s level of concern.

### Page 45 of 64 Table 6.2. Short-Term and Intermediate- Term Aggregate Risk Calculations

Short- and Intermediate-Term Scenario Population

NOAEL (mg/kg/day) LOC 1 Max

Allowable Exposure 2
(mg/kg/day) Average

Food &

Water Exposure 3
(mg/kg/day) Residential Exposure 4
(mg/kg/day) Aggregate MOE (food and residential) 5

Adult Male 3 100 0.03 0.002772 0.003626 470

Adult Female 3 100 0.03 0.002307 0.003626 510

Child (shortterm) 3 100 0.03 0.006252 0.0075 220

Child(intermediateterm) 3 100 0.03 0.006252 0.0081 210

1 This is based on the conventional uncertainty factor of 100x (10x for interspecies extrapolation and 10x for intraspecies variation).

2 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC.

3 Dietary exposures for these populations are based on the following population subgroups: Adult Male: U.S. population; Adult Female: Females 13-49 year s old; and Child: Children 1-2 years old.

4 Residential Exposure (RE) for adults = dermal exposure (intermediate-term dermal exposure from turf application via belly grinder (0.000904 mg/kg/day, Table 5.1.1) + postapplication dermal exposure from high contact with treated turf) (0.0027 mg/kg/day, Table 5.2.1.5) and short- and intermediate-term inhalation exposure from application via belly grinder (0.000022 mg/kg/day, Table 5.1.1). Residential Exposure (RE) for child (short-term) = incidental oral exposure (postapplication) of 0.0075 mg/kg/day (Table 5.2.1.2). Residential Exposure (RE) for child (intermediate-term) = dermal exposure (postapplication exposure from contact with treated turf [0.0045 mg/kg/day, Table 5.2.1.5] + incidental oral exposure (postapplication) of 0.0036 mg/kg/day (Table 5.2.1.5).

5 Aggregate MOE = [NOAEL ÷ (Avg Food & Water Exposure + Residential Exposure)].



### 6.3 Long-Term Aggregate Risk

There is potential chronic exposure via dietary (food and drinking water) exposure. Refer to

Section 4.2.

6.4 Cancer Aggregate Risk

Fluoxastrobin is classified as “ not likely to be carcinoge nic to humans;” ther efore, an aggregate

cancer assessment was not conducted.

7.0 Cumulative Risk Char acterization/Assessment

Unlike other pesticides for which EPA has fo llowed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to fluoxastrobin and any other subs tances and fluoxastrobin does not appear to produce a toxic

### Page 46 of 64 metabolite produced by other substances. For the purposes of this tolerance action, therefore,

EPA has not assumed that fluoxastrobin has a common mechanism of to xicity with other substances. For information regarding EPA's ef forts to determine which chemicals have a common mechanism of toxicity and to evaluate th e cumulative effects of such chemicals, see the policy statements released by EPA's Office of Pesticide Programs concerning common mechanism determinations and proc edures for cumulating effects from substances found to have

a common mechanism on EPA's website at http://www.epa.gov/ pesticides/cumulative/.

8.0 Occupational Exposure/Risk Pathway

Reference: Fluoxastrobin: Occupational and Residential Exposure Asse ssment for Proposed Field Uses on Sweet Corn, Field/Sweet Corn Grown for Seed, and Wheat, DP#367052, B. O’Keefe, 2/19/10.



### 8.1 Short- and Intermediate-Term Handler Risk

Fluoxastrobin can be applied to sweet corn, fiel d corn/sweet corn grown for seed, and wheat using aerial, chemigation, and groundboom appl ication equipment. Handler exposure is expected to be short- or inte rmediate-term based on informati on provided on proposed labels.

Chemical-specific data for assessing e xposure during pesticid e handling activities (mixing/loading, applying, and flagging) were not submitted to the Agency in support of this Section 3 application. It is HED policy to use data from PHED Version 1.1 to assess handler exposures for regulatory actions when chemical-s pecific data are not av ailable (HED Science Advisory Council for Exposure, SOP No.7, January 1999).

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 allowing for 100% bioavailability, fluoxastrobin is rapidly and nearly totally excreted in the urine and feces within 48 hours. Following an 8-hour dermal applicatio n 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 de rmal absorption value at 2.3% for risk

assessment purposes.

Since the short- and intermediate-term inhalati on endpoint was based on an oral study (90-day subchronic feeding study in the dog), and 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.

Summaries of the risks for occupational handl ers are included in Table 8.1. The maximum application rate for each exposure scenario is presented as the wo rst-case scenario. All handler scenarios resulted in MOEs greater than the leve l of concern (i.e., an MOE = 100) at some level of risk mitigation.

### Page 47 of 64 Dermal The proposed label proposes baselin e clothing attire (i.e., long sleeve shirt, long pants, shoes, and socks) plus chemical resistant gloves as PPE. The intermediate-term dermal risks do not exceed

HED’s level of concern with base line attire (i.e., long-sleeve shirt, long pants, shoes, and socks) for all scenarios, except the following which require chemical resistant gloves in addition to baseline clothing:

• 

### mixing/loading liquid concentr ates to support aerial appl ications to sweet corn, field/sweet corn grown for seed, and wheat; and

• 

### mixing/loading liquid concentrat es to support chemigation a pplications to sweet corn, field/sweet corn grown for seed, and wheat.

Only engineering control (enclosed cockpit) da ta are available to assess intermediate-term dermal risks to handlers operati ng aircraft. The intermediate-term dermal risks are not of concern to HED (i.e., MOEs ≥ 100) for pilots using enclosed cockpits and wearing baseline

attire.

Inhalation

The short- and intermediate-term inhalation risk s to handlers are not of concern to HED (i.e.,

MOEs ≥ 100) at baseline (no respirator) for any of the handler scenarios. Only engineering control (enclosed cockpit) data are available to assess short- and intermediate-term inhalation risks to handlers opera ting aircraft. The short- and inte rmediate-term inhalation risks do not exceed HED’s level of concern for pilots using enclosed cockpits and wearing no respirator.

Combined Combined intermediate-term dermal plus in termediate-term inhalation risks do not exceed HED’s level of concern, provide d personal protective equipment listed for intermediate-term dermal risks are worn (see Dermal above).Page 48 of 64Table 8.1. Agricultural HandlerExposure and Risk for FluoxastrobinUnit Exposurec,d,eDosef,g(mg/kg/day)MOEsh,i,j,kExposureScenarioCrop orTargetAppRatea(lbai/A)AcresTreatedDailybIntermediateTermBaselineDermal(mg/lb ai)IntermediateTermPPE-GDermal(mg/lb ai)Short- &IntermediateTermBaselineInhalation(μg/lb ai)BaselineDermald,hPPE-GDermaliBaselineInhalationeBaselineDermalfPPE-GDermalBaselineInhalationgIntermediateTermCombinedBaselineDermal +InhalationjIntermediateTermCombinedPPE-G +BaselineInhalationkMixer/LoaderWheat0.121,2002.90.0231.20.140.00110.0025222,8001,20021840Sweet corn0.123502.90.0231.20.040.000320.00072759,5004,200742,900Mixing/LoadingLiquidConcentratesfor AerialApplicationsField/Sweetcorn grownfor seed0.183502.90.0231.20.060.000480.0011506,3002,800491,900Field/Sweetcorn grownfor seed0.183502.90.0231.20.060.000480.0011506,3002,800491,900Mixing/LoadingLiquidConcentratesforChemigationApplicationsSweet cornand Wheat0.123502.90.0231.20.040.000320.00072759,5004,200742,900Wheat0.122002.90.0231.20.0230.000180.0004113017,0007,3001305,100Sweet corn0.12802.90.0231.20.00910.0000730.0001633041,00018,00032013,000Mixing/LoadingLiquidsConcentratesforGroundboomApplicationsField/Sweetcorn grownfor seed0.18802.90.0231.20.0140.000110.0002522028,00012,0002108,400ApplicatorApplyingSprays viaAerialWheat0.121,2000.005 (eng.control)No Data0.068(eng.control)0.00024(eng.control)No Data0.00014(eng.control)13,000(eng.control)No Data21,000(eng.control)8,000(eng.control)No DataPage 49 of 64Table 8.1. Agricultural HandlerExposure and Risk for FluoxastrobinUnit Exposurec,d,eDosef,g(mg/kg/day)MOEsh,i,j,kExposureScenarioCrop orTargetAppRatea(lbai/A)AcresTreatedDailybIntermediateTermBaselineDermal(mg/lb ai)IntermediateTermPPE-GDermal(mg/lb ai)Short- &IntermediateTermBaselineInhalation(μg/lb ai)BaselineDermald,hPPE-GDermaliBaselineInhalationeBaselineDermalfPPE-GDermalBaselineInhalationgIntermediateTermCombinedBaselineDermal +InhalationjIntermediateTermCombinedPPE-G +BaselineInhalationkEquipmentSweet corn0.123500.005 (eng.control)No Data0.068(eng.control)0.000069(eng.control)No Data0.000041(eng.control)43,000(eng.control)No Data74,000(eng.control)27,000(eng.control)No DataApplyingSprays viaAerialEquipment(continued)Field/Sweetcorn grownfor seed0.183500.005 (eng.control)No Data0.068(eng.control)0.0001(eng.control)No Data0.000061(eng.control)29,000(eng.control)No Data49,000(eng.control)18,000(eng.control)No DataWheat0.122000.0140.0140.740.000110.000110.0002527,00027,00012,0008,2008,200Sweet corn0.12800.0140.0140.740.0000440.0000440.000168,00068,00030,00021,00021,000ApplyingSprays viaGroundboomEquipmentField/Sweetcorn grownfor seed0.18800.0140.0140.740.0000660.0000660.0001545,00045,00020,00014,00014,000FlaggerSweet cornand Wheat0.123500.011Notapplicable0.350.00015Notapplicable0.0002120,000Notapplicable14,0008,300NotapplicableFlagging forAerial SpraysApplicationsField/Sweetcorn grownfor seed0.183500.011Notapplicable0.350.00023Notapplicable0.0003213,000Notapplicable9,5005,500Notapplicablea. Application Rates based on proposed uses on label for fluoxastrobin product Fluoxastrobin 480 SC Fungicide (EPA Reg. 66330-64).b. Science Advisory Council Policy # 9.1c. Unit Exposures based on PHED Version 1.1. Engineering control unit exposure for applying sprays via aerial equipment = enclosed cockpit.d. Baseline Dermal: Long-sleeve shirt, long pants,and no gloves; Baseline Inhalation: no respirator.e. Baseline plus Gloves Dermal: Baseline plus chemical-resistant gloves.f. Dermal Dose (mg/kg/day) = daily unit exposure (mg/lb ai) x application rate (lb ai/acre) x acres treated x dermal absorption factor (2.3%) / body weight (70 kg adult).g. Inhalation Dose (mg/kg/day) daily unit exposure (μg/lb ai) x application rate (lb ai/acre) x acres treatedx inhalation absorption (100%) / body weight (70 kg adult).h. Dermal MOE = NOAEL (3.0 mg/kg/day) / dermaldaily dose (mg/kg/day).Level of concern = 100.Page 50 of 64i. Inhalation MOE = NOAEL (3.0 mg/kg/day) / inhalation daily dose (mg/kg/day). Level of concern = 100.j. Combined Baseline Dermal + Inhalation MOE = 1 / (1/Baseline Dermal MOE) + (1/Baseline Inhalation MOE).k. Combined PPE-G + Baseline Inhalation MOE = 1 / (1/PPE-G DermalMOE) + (1/Baseline Inhalation MOE). Those risks specified asengineering control representenclosed cockpit application

### Page 51 of 64 8.2 Short- and Intermediate-Term Postapplication Exposure/Risk

Inhalation: Based on the Agency's current practices, a quantitative postapplication inhalation exposure assessment was not performed for fluoxast robin at this time primarily because it has a very low vapor pressure. Howe ver, volatilization of pesticides may be a potential source of postapplication inhalation exposure to individuals nearby to pestic ide applications. The Agency sought expert advice and input on is sues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rode nticide 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/SA P/meetings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report and may, as appropriate, develop policies and procedures to identify the need for and, subsequently, th e way to incorporate pos tapplication inhalation exposure into the Agency's risk assessments. If ne w policies or procedures are put into place, the Agency may revisit the need fo r a quantitative post application inhalation exposure assessment

for fluoxastrobin.

Dermal: There is the possibility for agricultural workers to have postapplication dermal

exposure to fluoxastrobin 

### following its proposed agricultural crop uses. Therefore, occupational intermediate-term dermal postapp lication risks were assessed.

There were no chemical-specific dislodgeable folia r residue (DFR) data to assess postapplication risks to workers while performing ta sks related to crops treated with fluoxastrobin 

### . Occupational postapplication exposures and ri sks were assessed using HED’ s default assumptions that 20 percent of the initial a pplication is available fo r transfer on day 0 (i.e., 12 hours after application) and that the residue dissipates at a rate of 10 percent per day.

HED uses a concept known as the transfer coefficient to numerically represent the postapplication exposures one would r eceive (generally presented as cm 2 

### /hour). A transfer

coefficient is a measure of the residue transfe rred from a treated surface to a person who is doing a task or activity in a treated ar ea. These values are the ratio of an exposure for a given task or activity to the amount of pesticide residue on tr eated surfaces available for transfer. HED has developed a series of standard tr ansfer coefficients that are unique for a variety of job tasks or

activities that are used in lieu of chemi cal- 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 ta sks that postapplication workers might perform on each crop grouping.

HED assumes an 8-hour workday for postapplication workers and assumes 70 kg for an adult (average adult weight).

For fluoxastrobin, the exposure durations for non cancer postapplication risk assessment were short-term and intermediate-term. However, sinc e there is no dermal toxi cological endpoint of concern for short-term exposures, postapplication risks are presented only for intermediate-term

### Page 52 of 64 dermal exposures. The level of concern (LOC ) for occupational postapplication risk is for margins of exposure (MOEs) of 100 (i.e., an MOE <100 is of concern).

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

DE (t) 

### (mg/day) = (DFR (t) 

### (μg/cm 2 

### ) x TC (cm 2 

### /hr) x Hr/Day) x DA / 1,000 (μg/mg)

Where: DE(t) = Dermal exposure or amount deposite d 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” (μg/cm 2 

### ), TC = Transfer Coefficient (cm 2 

### /hour), Hr/day = Exposure duration meant to repr esent a typical workday (8 hours), and DA = Dermal absorption factor (0.023)

Where: Default DFR (μg/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 μg/lb, and

CF2 = 2.47E-8 A/cm 2



### .

Table 8.2.1 presents the default DFR values on day 0 (12 hours after application) that were used for this postapplication expos ure and risk assessment.

Table 8.2.1. Summary of DFRs by Crop Grouping Based on HED Default Assumptions

Crop Application rate (lb ai/acre) Fraction of

ai retained

on the foliage Conversion

Factor 1 (μg/lb) Conversion

Factor 2 (A/cm 2 ) Day after Application Default DFR (μg/cm 2 ) 1

Sweet corn and

Wheat 0.12 0.269

Field/Sweet corn

grown for seed 0.18 20% (Default) 4.54E+8 2.47E-8 0 (12 hours)
0.404

1 Default DFR (μg/cm 2 ) = AR (lb ai/A) x F x (1- D) t x CF1 x CF2, where F is 0.20, t = 0, CF1 is 4.54E+8 ug/lb, and

CF2 is 2.47E-8 A/cm 2

.



### The postapplication exposure associated with agricultural crops is summarized in Table 8.2.2. 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 applica tion) and, therefore,

risks do not exceed HED’s level of concern.

### Page 53 of 64 Table 8.2.2. Summary of Occupational Postapplication Risks with HED Default Assumptions 1,2,3

Crop Grouping Application

rate (lb ai/acre) Default

DFR ( μ g/cm 2 ) Maximum Transfer Coefficient (μg/cm 2 ) Day after Application MOE 4
(Level of Concer n = 100)

Field/Sweet

corn grown

for seed 0.18 0.404 17,000 (Detasseling, Hand Harvesting) 0 (12 hours) 170

Sweet corn 0.12 0.269 17,000 (Detasseling, Hand Harvesting) 0 (12 hours) 250

Wheat 0.12 0.269 1,500 (Scouting and Irrigating) 0 (12 hours) 2,800

1 Crops were assessed using the highes t transfer coefficient available.

2 DE (t) (mg/day) = (DFR (t) (μg/cm 2 ) x TC (cm 2 /hr) x 8 Hr/Day) x DA / 1,000 (μg/mg), where DA is 0.023.

3 Daily Dose (mg/kg/day) = DE (t) (mg/day) ÷ 70 kg.

4 MOE = NOAEL (3.0 mg/kg/day) ÷ Daily Dose (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 (WPS) fo r Agricultural Pesticides, active ingredients classified as acute Toxicity Ca tegories III or IV for these rout es are assigned a 12-hour REI. Therefore, the 12-hour REI that appear s on the proposed label is adequate.

### Page 54 of 64 9.0 Data Needs and Label Recommendations

9.1 Toxicology

Guideline Number: 870.7800 Study Title : Immunotoxicity Rationale for Requiring the Data



### This is a new data requirement under 40 CFR Pa rt 158 as a part of the data requirements for registration of a pestic ide (food and non-food uses).

The Immunotoxicity Test Guideline (OPPTS 870.7800) prescribes functional immunotoxicity testing and is designed to eval uate the potential of a repeated chemical exposure to produce adverse effects (i.e ., suppression) on the immune system. Immunosuppression is a deficit in the ability of the immune system to respond to a challenge of bacterial or vira l infections such as tuberc ulosis (TB), Severe Acquired Respiratory Syndrome (SARS), or neoplasia . Because the immune system is highly complex, studies assessing functional i mmunotoxic endpoints are helpful in fully characterizing a pesticide’s pot ential immunotoxicity. These data will be used in combination with data from hematology, lym phoid organ weights, and histopathology in routine chronic or subchronic toxicity st udies to characterize potential immunotoxic

effects.

Practical Utility of the Data

How will the data be used?



### These animal studies can be used to select endpoints and doses for use in risk assessment of all exposure scenarios and are considered a primary data source for reliable reference dose calculation. For example, animal studies have demonstrated that immunotoxicity in

rodents is one of the more sensitive manifestations of TCDD (2,3,7,8-tetrachlorodibenzop-dioxin) among developmental, reproduc tive, and endocrinol ogic toxicities. Additionally, the EPA has established an oral reference dose (RfD) for tributyltin oxide (TBTO) based on observed immunotoxici ty in animal studies (IRIS, 1997).

How could the data impact the Agency's future decision-making?



### If the immunotoxicity study show s that the test material pos es either a greater or a diminished risk than that given in the inte rim decision’s conclusion, the risk assessments for the test material may need to be revise d to reflect the magnitude of potential risk

derived from the new data.

If the Agency does not have this data, a 10x database uncertainty factor may be applied for conducting a risk assessment from the available studies.

### Page 55 of 64 9.2 Residue Chemistry

860.1200 Directions for Use

• The proposed use directions for sweet corn s hould be revised to specify a minimum PHI for corn stover of 23 days.

• The proposed use directions for wheat s hould be revised to include the following statement: Make no more than one applica tion prior to harvest of wheat forage.

• The Section B/label must be revised to indi cate use on field corn/sweet corn grown for

seed rather than on seed corn sinc e no tolerances exist for pop corn.

860.1500 Crop Field Trials

• Two additional sweet corn field trials re flecting the proposed us e pattern must be

conducted in Zones 1 and 5.

• Two additional wheat field trials reflecting th e proposed use pattern must be conducted in

Zone 8.

• All additional field trials should include an adjuvant (sweet corn) or crop oil concentrate (wheat).

860.1550 Proposed Tolerances

• The proposed tolerance of 0.02 ppm for sweet corn K+CWHR is too high; a tolerance of 0.01 ppm should be proposed.

• The established tolerance for peanut at 0.010 ppm must be increased to 0.02 ppm due to over-tolerance residues in peanut nutmeat in the submitted processing study.

• The established tolerance for peanut, refi ned oil should be increased from 0.03 to 0.06 ppm based on the MTCF for peanut oil and the increased HAFT of 0.02 ppm in peanut

nutmeat.

• The proposed tolerance of 0.20 ppm for wheat bran is too high, and the proposed tolerance of 15 ppm for AGF based on the wheat processing study is t oo low; tolerances should be proposed at 0.15 ppm fo r wheat bran and 60 ppm for AGF.

### Page 56 of 64 9.3 Occupational and Residential Exposure

• Due to e-mail communication with Arysta, the label should be changed from “Do not apply more than 880 lbs of DISARM G per acr e per year” to “Do not apply more than 800 pounds DISARM G per acre per year” on page 9 under “Restrictions and Other

Information”.

References:

Fluoxastrobin. Petition for the Establishment of Permanen t Tolerances for Uses on Sweet Corn and Wheat. Submission of Peanut Processing Data in Response to Conditional Registration Requirements (PP#3F6556). Summary of Analytical Chemistry and Residue Data , DP#’s 364445 and 367049, M. Negussie, 1/20/10.

Fluoxastrobin: Chronic Dietary (Food and Drinking Water) Exposure Assessments for the Section 3 Registration Action Uses on Sweet Corn and Wheat (PP#9F7567) and Submission of Peanut Processing Data in Response to Conditional Registration Requirements (PP#3F6556), DP#367050, M. Negussie, 1/22/10.

Drinking Water Assessment to Support Fluoxastrobin Use on Sweet Corn and Wheat, DP#366189, R. Bohaty, Ph.D., 1/13/10.

Fluoxastrobin: Occupational and Residential Exposure Assessment for Proposed Field Uses on Sweet Corn,

Field/Sweet Corn Grown for Seed, and Wheat, DP#367052, B. O’Keefe, 2/19/10

.

Fluoxastrobin. Residential Exposure/Risk Assessment for Proposed Non-food Uses by Residential Handlers on Turf

Grasses , DP#371251, K. Rury, 3/4/10.

Fluoxastrobin. Human Health Risk Assessment for Proposed Uses on Field Corn, Soybean, and the Low-Growing Berry Subgroup 13-07G , DP#’s 356982 and 357473, N. Dodd, 8/13/09.

Fluoxastrobin. Petitions for the Establishment of Permanen t Tolerances for New Uses on Low-Growing Berry Crop Subgroup 13-07G (PP#8F7406), Soybean and Field Corn (PP#8F7437). Summary of Analytical Chemistry and
Residue Data, DP#356953, M. Negussie, 7/8/09.

Fluoxastrobin. Supplemental Residue Data for Livestock Metabolism, Residue Analytical Methods, Storage Stability, Crop Field Trials, and Rotational Crop Field Trials, Submitted to Fulfill Conditions of Registration for Fluoxastrobin 480 SC (EPA Reg. No. 66330-64), DP#334234, A. Acierto, 10/30/08.

PP#3F6556. Fluoxastrobin. Petition for the Establishment of Perm anent Tolerances for Use on Peanuts, Tuberous and Corm Vegetables Subgroup, Leaf Petiole Vegetables Subgroup, Fruiting Vegetables Group, and Seed Treatment of Peanut and Potato, DP#’s 289106 and 289107, W. Wassell, 1/25/05.

Fluoxastrobin: Human Health Risk Assessment for Proposed Uses on Peanuts, Tuberous and Corm Vegetables (Subgroup 1C), Leaf Petiole Vegetables (Subgroup 4B), Fruiting Vegetables (Group 8), Turf, and as a Seed Treatment on Potato (Seed Piece), Peanut and Turf, DP#292422, S. Winfield, 1/24/05.

HED/RAB3 fluoxastrobin hazard meetings, October and November 2004.

### Page 57 of 64 Appendix A: Toxicology Assessment

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for food use for fluoxastrobin are in Table A.1. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Table A.1. Toxicology Da ta Requirements for Food Use

Technical Test

Required Satisfied

870.1100 Acut e Oral T oxicity....................................................... 870.1200 Acute Dermal Toxicity ..................................................

870.1300 Acute Inhalation To xicity..............................................

870.2400 Primar y Eye Irr itation....................................................

870.2500 Primar y Dermal Irritation ..............................................

870.2600 Derm al Sensiti zation...................................................... yes

yes

yes

yes

yes

yes yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (r odent) ...............................................

870.3150 Oral Su bchronic (nonr odent) ......................................... 870.3200 21-Day Dermal .............................................................. 870.3250 90-Day Dermal ..............................................................

870.3465 90-D ay Inhalation.......................................................... yes

yes

yes CR 1

CR 1 yes

yes

yes
NR 1

NR 1

870.3700a Developmenta l Toxicity (rodent)................................... 870.3700b Developmental Toxicity (nonrodent)............................. 870.3800 Reproduction ................................................................. yes

yes

yes yes

yes

yes

870.4100a Chronic T oxicity (rodent) ..............................................

870.4100b Chronic Toxi city (nonrodent)........................................ 870.4200a Oncoge nicity (rat).......................................................... 870.4200b Oncogenicity (mouse)....................................................

870.4300 Chro nic/Oncoge nicity

.................................................... -
yes

- yes

yes -
yes

- yes

yes

870.5100 Mutagenicity—G ene Mutation - bacterial..................... 870.5300 Mutagenicity—Gene Mutation - mammalian................ 870.5375 Mutagenicity—Struc tural Chromosomal Aberrations... 870.5395 Mutagenicity—O ther Genotoxic Effects....................... yes

yes

yes

yes yes

yes

yes

yes

870.6100a Acute Delaye d Neurotox. (hen) ..................................... 870.6100b 90-Day Neurotoxicity (hen)...........................................

870.6200a Acute Neurotox. Screening Batte ry (rat) ....................... 870.6200b 90-Day Neuro. Screening Batte ry (rat).......................... 870.6300 Develop. Neuro.............................................................. no

no
NR 1

CR 1

no -

-
yes

yes

-

870.7485 Gene ral Metabo lism ......................................................

870.7600 Dermal Penetration........................................................

870.7800 Immunotoxicity ............................................................. yes

yes

yes yes

yes

no

Special Studies for Ocular Effects Acute Oral (rat)...........................................................

Subchronic Or al (rat) .................................................. Six-month Oral (dog)..................................................

1 CR = Conditionally required; NR = Not required.

### Page 58 of 64 A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Profile - Fluoxastrobin

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral - rat 45865612 LD 50 >2000 mg/kg III

870.1200 Acute dermal - rat 45865613 LD 50 >2000 mg/kg III

870.1300 Acute inhalation - rat 45865618 LC 50 = 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

-

### DRAFT – INTERNAL AND DELIBERA TIVE- DO NOT CITE OR QUOTE

Page 59 of 64 Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile – Fluoxastrobin

Guideline No./

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

870.3100 90-Day oral toxicity (rats) 45865627 (1998); /acce ptable/guideline / M: 0, 125, 1000 or 8000 ppm (0, 8.7, 70.4 or 580.0 mg/kg/day) F: 0, 250, 2000 or 16000 ppm (0, 21.5, 162.9 or 1416.1 mg/kg/day) NOAEL = M: 70.4 mg/kg/day; F: 162.9 mg/kg/day LOAEL = M: 580.0 mg/kg/day based on reduced body weight gain and food intake, vacuolation in the zona fasciculate of the adrenal cortex, calculi in the urethra and kidney, and histological lesions in kidney, urinary bladder, and urethra. LOAEL = F: 1416.1 mg/kg/day based on increased liver weight (by 20%).

870.3100 90-Day oral toxicity (mice) 45865626 (1998) /accepta ble/non-guideline / 0, 450, 1800 or 7000 ppm M: 0, 81.1, 313.4 or 1303.7 mg/kg bw/day F: 0, 135.1, 539.2 or 2256.9 mg/kg/day NOAEL/LOAEL were not assigned. There was dose related increase of liver weight in both sexes and in kidney weight in females, in addition to other effects whose toxicological relevance was considered uncertain. Among these effects were increased hepatocellular hypertrophy with cytoplasmi c changes in the high-dose males and minimal to moderate kidney tubular hypertrophy in mid- and high-dose females.

870.3150 90-Day oral toxicity (dogs) 45865629 (2001); 45865628 (2001); 45865722 (2000) / acceptable/guideline / 4 beagle dogs/sex/dose (MRID 45865629): 0, 25, 50, 100, 800 or 2500 ppm M: 0, 0.7, 1.4, 3.0, 24.8 or 76.0 mg/kg/day F: 0, 0.7, 1.5, 3.0, 24.2 or 75.0 mg/kg/day NOAEL = M/F: 3.0 mg/kg/day (100 ppm) 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 toxi city findings in the liver in both sexes (cholestasis) and in kidneys (increased relative weights in females and degeneration of the proximal tubular epithelium in males).

870.3200 28-Day dermal toxicity (rats) 45865630 (2000) / acceptable/guideline / 0, 100, 300 or 1000 mg/kg bw/day (6 hours/day, 5 days/week for the first three weeks; 7 days/week for the fourth week) NOAEL = 1000 mg/kg/day (the limit dose, for both systemic and dermal)

LOAEL not identified.

870.3700a

Prenatal developmental (rats) 45865631 (1997) / acceptable/guideline 0, 100, 300 or 1000 mg/kg bw/day Maternal NOAEL ≥ 1000 mg/kg bw/day (limit dose)

LOAEL not identified.
Developmental NOAEL ≥ 1000 mg/kg bw/day

LOAEL not identified.

870.3700b

Prenatal developmental (rabbits) 45865632 (1999) / acceptable/guideline / 22 naturally mated female Himalayan rabbits/group by gavage: 0, 25, 100, 400 mg/kg/day Materna l NOAEL = 100 mg/kg/day LOAEL = 400 mg/kg/day based on cold ears, transient body weight loss, and decreased food consumption.
Developmenta l NOAEL ≥ 400 mg/kg/day

LOAEL not identified.

870.3800 Reproduction and fertility effects (rats) 45865633 (2001); 45865634 (2001) / acceptable/guideline / 0, 100, 1000 or 10000 ppm M: 0, 6.3, 70.0 or 665.0 mg/kg bw/day F: 0, 7.8, 84.7 or 825.4 mg/kg bw/day Parental Systemic NOAEL = M/F 70.0/84.7 mg/kg/day LOAEL = M/F 665.0/825.4 g/kg/day based on decreased premating body weight gain of the P-generation males and females and decreased premating absolute body weight of the F 1 males and females. Reproductive NOAEL = M/F > 665.0/825.4 mg/kg/day

### Page 60 of 64 Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile – Fluoxastrobin

Guideline No./

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

LOAEL not identified. Offspring NOAEL = M/F 70.0/84.7 mg/kg/day LOAEL = M/F 665.0/825.4 mg/kg/day based on decreased body weights, delayed preputial separation, and incomplete ossification in the F 1 and/or F 2 males and

females.

870.4100b Chronic toxicity (dogs) 45865701 (2002); 45865722 (2000) / acceptable/guideline / 4 beagle dogs/sex/dose: 0, 25, 50, 250 or 1200 ppm M: 0, 0.8, 1.7, 8.1 or 34.9 mg/kg bw/day F: 0, 0.7, 1.5, 7.7 or 37.4 mg/kg/day NOAEL = M/F:1.7/1.5 mg/kg/day LOAEL = M/F:8.1/7.7 mg/kg/day based on body weight reductions and hepatocytomegaly and cytoplasmic changes associated with in creased serum liver alkaline phosphatase indicative of cholestasis.

870.4200b Carcinogenicity (mice) 45865702 (2001) / acceptable/guideline / 0, 100, 700 or 4200 ppm M: 0, 18.5, 135.4 or 775.6 mg/kg bw/day F: 0, 29.5, 204.0 or 1265.1 mg/kg bw/day NOAEL = M/F: 775.6/1265.1 mg/kg bw/day

LOAEL not identified. No evidence of carcinogenicity

.

870.4300

Combined chronic toxicity/ carcinogenicity (rats) 45865703 (2001) / acceptable/guideline /

M: 0, 40, 100, 1000 or 5000 ppm (0, 2.1, 5.2, 53.0 and 271.9 mg/kg/day) F: 0, 100, 500, 2500 or 12500 ppm (0, 6.9, 35.2, 181.3 and 1083.2 mg/kg/day) NOAEL = M/F: 53.0/181.3 mg/kg/day LOAEL = M/F: 271.9/1083.2 mg/kg/day based on decreased body weight, body weight gain, and food efficiency in both sexes, decreased spleen weight in males, and microscopic lesions in the uterus of females.

There is no evidence of carcinogenicity (ad hoc senior CARC member meeting on 10/25/2004).

870.6200a

Acute neurotoxicity screening battery (rats) 45865712 (2001) / acceptable/guideline / 12 rats/sex: 0, 200, 500 or 2000 mg/kg bw NOAEL (neurotoxic) ≥ 2000 mg/kg (limit dose)

LOAEL not identified.

870.6200b

Subchronic neurotoxicity screening battery (rats) 45865713 (2002) / acceptable/guideline / 12 rats/sex: 0, 200, 1000, 7500 ppm M: 0, 12.7, 59.5 or 473.9 mg/day F: 0, 15.1, 71.7 or 582.4 mg/kg/day NOAEL (systemic and neurotoxic) = M/F: 473.9/582.4 mg/kg/day

LOAEL not identified.

Gene Mutation

870.5100 In

vitro bacterial

reverse gene mutation 45865704 (1996) / acceptable/guideline / plate incorporation: 16, 50, 158, 500, 1581 and 5000 ug/plate; following preincubation: 10, 32, 100, 316, 1000 and 3162 ug/plate negative (considered non-mutagenic in Salmonella typhimurium cultures treated up to cytotoxic/precipitating levels)

### Page 61 of 64 Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile – Fluoxastrobin

Guideline No./

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

Gene Mutation

870.5100 In

vitro bacterial

reverse gene mutation 45865705 (1998) / acceptable/guideline / plate incorporation and following preincubation: 16, 50, 158, 500, 1581 and 5000 ug/plate Test substance: HEC 5725N (E:Z = 90:10%) negative (considered non-mutagenic in this Salmonella typhimurium /microsome test)

Gene Mutation

870.5100 In

vitro bacterial

reverse gene mutation 45865706 (2000) / unacceptable/guideline / plate incorporation: 16, 50, 158, 500, 1581 and 5000 ug/plate; following preincubation: 100, 200, 400, 800, 1600 and 3200 ug/plateTest substance: HEC 5725-phenoxyhydroxy-pyrimidine negative (considered non-mutagenic in this Salmonella typhimurium /mammalian activation gene mutation assay)

Gene Mutation

870.5100 In

vitro bacterial

reverse gene mutation 45865707 (2001) / acceptable/guideline / plate incorporation: 16, 50, 158, 500, 1581 and 5000 ug/plate; following preincubation: 5, 16, 50, 158, 500 and 1581 ug/plateTest substance: HEC 5725-phenoxyhydroxy-pyrimidine negative (considered non-mutagenic in this Salmonella typhimurium /mammalian activation gene mutation assay)

Gene Mutation

870.5100 In

vitro bacterial

reverse gene mutation 45865708 (2001) / unacceptable/guideline / 16 to 5000 ug/plate (6 concentrations)

Test substance: HEC 5725-dihydroxypyrimidine negative (considered non-mutagenic in this Salmonella typhimurium /mammalian activation gene mutation assay)

870.7600

Dermal penetration (monkey) 45911501/45911502 (2003) Acceptable/NonGuideline 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 was 2.31%.

870.7800 Immunotoxicity

- Mouse (Subchronic Feeding Study) 45865726 (2001) Unacceptable/guideline 0, 450, 1800, or 7000 ppm (equivalent to 0, 106.8, 367.3, and 1534.4 mg/kg/day for males and 0, 157.3, 659.6, and 2383.3 mg/kg/day for females) No clinical signs of toxicity or mortality were found and no treatment-related effects were found on body weight, food intake, or B-cell activ ated, T-cell mediated IgM response to SRBC. However, the study is considered unacceptable because of uncertainty in dietary test material intake, failure to re port spleen weight of each mouse at necropsy, and failure of the laboratory to demonstrate its capability in performing this type of

assay.

### Page 62 of 64 Appendix B: Metabolism Assessment

Table B. Chemical Names and Structures of Fluoxastrobin ( Z -Isomer), the E -Isomer, and HEC7154 1

Company Name

Matrix Chemical Name Structure 1

Fluoxastrobin, E -isomer [Parent]

Peanut hay Tomato fruit Wheat forage, hay, straw, and

grain Rotated Swiss chard, turnip tops and roots, and wheat forage, hay, straw, and grain Goat milk, muscle, fat, liver,

and kidney Hen egg, liver, muscle, and fat (1 E )-[2-[[6-(2-chlorophenoxy)-

5-fluoro-4- pyrimidinyl]oxy]phenyl](5,6- dihydro-1,4,2-dioxazin-3- yl)methanone O -methyloxime O

Cl

O

N N F

O O N

N
O

CH 3

Fluoxastrobin, Z- isomer [Isomer of parent, not

pesticidally active, proposed for regulation in plant and animal commodities]

Peanut hay Tomato fruit Wheat forage, hay, straw, and

grain Rotated Swiss chard, turnip tops and roots, and wheat forage, hay, straw, and grain Goat fat and liver Hen egg, muscle, and fat (1 Z )-[2-[[6-(2-chlorophenoxy)-

5-fluoro-4- pyrimidinyl]oxy]phenyl](5,6- dihydro-1,4,2-dioxazin-3- yl)methanone O -methyloxime O

Cl

O

N N F

O O N

N
O

CH 3

Phenoxy-hydroxypyrimidine

metabolite [HEC7154] [Metabolite proposed for

regulation in livestock commodities]

Peanut hay (glucose conjugate also identified) Wheat hay and straw Goat milk, muscle, fat, liver,

and kidney Hen egg, liver, muscle, and fat 6-(2-chlorophenoxy)-5-fluoro-4- pyrimidinol F Cl

O

N N OH

1 For chemical names and structures of additional transformation products, refer to the Residue Chemistry Summary Document (DP#398293, M. Negussie, 7/8/09).

### Page 63 of 64 Appendix C: Physical and Chemical Properties

Table 2.3. Physicochemical Properti es of Technical Grade Fluoxastrobin.

Parameter Value Reference

Molecular Weight 458.8 amu

Melting range 103-105 ° C MRID 45865525

pH 6.3 (1% in CIPAC-D water) MRID 45865520

Density 1.4216 g/cm 3 MRID 45865303

Water solubility at 20 ° C : 0.0019 g/L; 0.0024 g/L at pH 4 0.0023 g/L at pH 7 0.00227 g/L at pH 9 MRIDs 45865520, 45865525

Solvent solubility at 20 ° C : n-heptane 0.05 g/L xylene 38 g/L

dichloromethane >250 g/L 2-propanol 6.7 g/L

1-octanol 1.1 g/L polyethylenglycol 400 119 g/L

acetone >250 g/L ethyl acetate >250 g/L

acetonitrile >250 g/L dimethylsulfoxide >250 g/L MRIDs 45865520, 45865525

Vapor pressure 5.63x10 -10 Pa (20 ° C)

8.72x10 -10 Pa (25 ° C) MRID 45865525

Dissociation constant, pK

a no dissociation constant at pH 4-9 MRID 45865303

Octanol/water partition coefficient, Log(P OW ) 2.85 (20 ° C); P OW = 708 MRID 45865525

UV/visible absorption spectrum 19,358 L/mol

⋅ cm at 250 nm MRID 45865303

### Page 64 of 64 Appendix D: Review of Human Research

Studies reviewed for ethical conduct:

MRID 44972201 – ORETF data PHED Surrogate Exposure Guide

This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pest icide or other chemical. Thes e studies, which comprise the Pesticide Handler Exposure Database (PHED) and the Outdoor Residential Exposure Task Force (ORETF), have been determined to require a revi ew of their ethical condu ct and have received that review. In this assessment, ORETF data were used to assess loading/applying with a push type spreader (data from MRID 44972201) and PHED data were used to assess loading/applying with a belly grinder.

Studies reviewed by the Huma n Studies Review Board:

None.