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 Residential 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 residues 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 (1Z)-[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 residue chemistry deficiencies for PP#3F6556 on peanuts (DP#289106, 

W. Wassell, 1/25/05) have now been resolved (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 restriction preventing homeowner application to turf 

grasses on the current fluoxastrobin turf label (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 characterization and the 

rationale for toxicity endpoint selection will not be repeated in this risk assessment. However, 

the salient features will be summarized for these 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 petition were reviewed by Meheret Negussie, who 

also conducted the dietary assessment. The occupational/residential assessment for food uses on 

sweet corn, field corn/sweet corn grown for seed, 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 performed 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, there are no residue chemistry issues that would 

preclude granting conditional registration for the requested uses of fluoxastrobin on sweet corn 

Page 2 of 64 
and wheat or establishment of the following tolerances 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 wheat increase the livestock dietary burden and 

necessitate increasing certain established 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 fluoxastrobin were revised under 40 CFR §180.609 as 

follow: 

Under 40 CFR §180.609(a)(1): “Tolerances are established for 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 (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, (1Z)-[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.” 

Under 40 CFR §180.609(a)(2): “Tolerances are established for 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, (1E)-[2-[[6-(2-chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy]phenyl](5,6-

dihydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime, its Z-isomer, (1Z)-[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 stoichiometric equivalent of fluoxastrobin.” 

Under 40 CFR §180.609(d): “Tolerances are established for the indirect or inadvertent 

residues of fluoxastrobin, including is metabolites 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 determined by measuring only 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, (1Z)-[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 

Commodity Tolerance (ppm) 

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 byproducts 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 64 
Table 1. Tolerance Summary for Fluoxastrobin 

Commodity Tolerance (ppm) 

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 proposed 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 quantitation (LOQ) of the 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 grain, aspirated grain fractions (AGF) be increased from 15 

ppm to 60 ppm. The wheat processing study indicates 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 (HAFT) 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 grain, 

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 established tolerance of 0.010 ppm for peanut be increased to 0.02 

ppm since over-tolerance residues of 0.02 ppm were found in peanut nutmeat reflecting 

application at 1x the proposed use rate in the submitted processing study. 

HED recommends that the established tolerance of 0.030 ppm for peanut, refined oil be 

increased to 0.06 ppm. HED has considered the discrepancy between 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 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 (OPPTS 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, metabolism, 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 and 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 Degradates 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 Crop 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 Intermediate-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 with mitochondrial 

respiration in plant-pathogenic fungi, thus inhibiting spore germination and mycelial growth. It 

belongs to the strobilurin class of fungicides (Group 11), also termed methoxyacrylates. 

Fluoxastrobin is the accepted common name for the pesticidally active E-isomer of [2-[[6-(2-

chlorophenoxy)-5-fluoro-4-pyrimidinyl]oxy]phenyl](5,6-dihydro-1,4,2-dioxazin-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 field corn/sweet corn grown for 

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

The FLUOXASTROBIN 480 SC Fungicide label (EPA 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 FLUOXASTROBIN 480 SC Fungicide Seed Treatment. The 

current action on turf is a requested 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 broadcast foliar applications can be applied using 

ground, aerial, or chemigation equipment. For field corn/sweet corn grown for seed, two foliar 

applications can be made at the 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 applications 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 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 (REI) is 12 hours. 

For the registered use on peanuts, four broadcast foliar applications of EVITOTM 480 SC can be 

made at the rate of 0.18 lb ai/A/application for a maximum seasonal application 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 restriction preventing homeowner application to turf 

grasses on the registered fluoxastrobin turf label (DisarmTM G Fungicide, a 0.25% granular 

formulation; 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.” DisarmTM 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, parks, 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 cranked 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 fungal diseases in established turf. Optimum application timing for 

control of seedling diseases is just prior to, during, or after seeding. 

 

Human Health Risk Assessment: 

Toxicity/Hazard: The toxicology database provides sufficient 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 toxicity via the oral, dermal, and inhalation 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 toxicity in all tested species other than the dog 

which displayed adverse liver toxicity at considerably lower doses than those noted for other 

species. As the most sensitive species, the effects observed in the dog were used as endpoints in 

the risk assessment. In both the 90-day and one-year 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 incidences in uterine adenocarcinoma and thyroid 

follicular cell adenoma in the rat chronic toxicity/carcinogenicity study were determined to be 

unrelated to treatment. These observations, which 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-generation reproduction rat 

study, there was no increased susceptibility to prenatal or postnatal exposure to fluoxastrobin and 

no effects on reproduction. Furthermore, fluoxastrobin 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 following repeated dosing in the rat subchronic 

neurotoxicity study. Results of genotoxicity testing were negative and there were no treatmentrelated carcinogenicity findings in adequately performed carcinogenicity studies in rats and mice. 

Therefore, fluoxastrobin is classified under the March 2005 Cancer Guidelines as “not likely to 

be carcinogenic to humans.” 

The RAB3 fluoxastrobin team has determined that the1996 Food Quality Protection Act (FQPA) 

safety factor of 10X for protection of infants and children should be removed for all potential 

exposure scenarios to fluoxastrobin because 1) the toxicity database is adequate to characterize 

any potential for prenatal or postnatal risk for infants and children; 2) there is no indication of 

increased susceptibility to pre- and/or post-natal toxicity; 3) there is no indication of 

Page 9 of 64 
neurotoxicity; and 4) the exposure databases are complete or are 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 toxicity 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 intermediate-term inhalation, as well as the short- and 

intermediate-term incidental oral exposure scenarios. 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 not expected based on the proposed uses). An 

acute quantitative hazard estimate was not established because an adverse effect attributable to a 

single exposure was not identified from the available 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 concern in/on treated livestock 

commodities are fluoxastrobin, its Z-isomer, and its phenoxy-hydroxypyrimidine metabolite [6-

(2-chlorophenoxy)-5-fluoro-4-pyrimidinol]. The residues of concern 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 adverse effect attributable to a 

single dose. An acute reference dose (aRfD) was not established. 

Chronic Dietary Exposure/Risk: A conservative dietary exposure assessment was performed for 

fluoxastrobin. The assumptions of this dietary assessment included tolerance level residues and 

100% crop treated (CT). Based on processing studies, the processing factors for tomato puree, 

potato chips, dried potato (granules/flakes), and potato flour were reduced to 1. Separate 

tolerances were set for peanut oil, wheat bran and tomato paste; therefore, the processing factors 

for these commodities were set at 1. For all other processed commodities, DEEM version 7.81 

default processing factors were assumed. The estimated drinking water concentration (EDWC) 

value for chronic exposure, the 1-in-10 year annual mean value of 33 ppb, was directly 

incorporated into the dietary assessment. The results of the chronic dietary (food and drinking 

water) analysis are less than 100% of the chronic 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 Committee (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 residential handler exposure from loading 

and applying granular fluoxastrobin. 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 dermal + intermediate-term inhalation) MOEs were 

not of concern to HED (i.e., MOE ≥ 100). 

Residential Postapplication Exposure: For existing uses on registered 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 residential postapplication scenarios. The MOEs for 

residential postapplication exposure to fluoxastrobin are all above 100, and therefore, do not 

exceed HED's level of concern. 

Aggregate Risk: 

Acute Aggregate Risk: Acute exposures were not considered because an adverse effect 

attributable to a single dose was not identified. 

Short-Term and Intermediate-Term Aggregate Risk: There is potential short- and intermediateterm exposure to fluoxastrobin via the dietary (food and drinking water) pathway (which is 

considered background exposure) and residential 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, these pathways lead to exposure via the oral 

(background), and incidental oral and dermal (primary) routes. All MOEs 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 exposure via the dietary (food and 

drinking water) pathway, but not through the residential 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 equipment. 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 intermediate-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 for the following scenarios which require chemical 

resistant gloves in addition to baseline clothing: 

• mixing/loading liquid concentrates to support aerial applications to sweet corn, field 

corn/sweet corn grown for seed, and wheat; and 

• mixing/loading liquid concentrates to support chemigation applications 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 fluoxastrobin 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 were assessed. All scenarios 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 environmental justice concerns, to 

the extent possible, were considered in this human health risk assessment, in accordance with 

U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority 

Populations and Low-Income Populations," 

http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. 

As a part of every pesticide risk assessment, OPP considers a large variety of consumer 

subgroups according to well-established procedures. In line with OPP policy, HED estimates 

risks to population subgroups from pesticide exposures that are based on patterns of that 

subgroup’s food and water consumption, and activities in and around the home that involve 

pesticide use in a residential setting. Extensive data on food consumption patterns are compiled 

by the USDA under the Continuing Survey of Food Intake by Individuals (CSFII) and are used 

in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed 

and categorized by subgroups based on age, season of the year, ethnic group, and region of the 

country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups 

and exposure assessments are performed when conditions or circumstances warrant. Whenever 

appropriate, non-dietary exposures based on home use of pesticide products and associated risks 

for adult applicators and for children (three to less than six years old), youths, and adults entering 

or playing on treated areas postapplication are evaluated. Further considerations are currently in 

development as OPP has committed resources and expertise to the development of specialized 

Page 12 of 64 
software and models that consider exposure to bystanders and farm workers as well as lifestyle 

and traditional dietary patterns among specific subgroups. 

Review of Human Research: This risk assessment relies in part on data from studies in which 

adult human subjects were intentionally exposed to a pesticide or other chemical. These studies 

(listed in Appendix D) have been determined to require a review of their 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 mitochondrial 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]phenyl](5,6-dihydro-1,4,2-dioxazin-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 (EPA 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 FLUOXASTROBIN 480 SC Fungicide Seed Treatment. The 

current action on turf is a requested 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 and corn (field, seed, and 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 corn, field corn/sweet corn grown for seed, and 

wheat, fluoxastrobin is formulated as a soluble concentrate (SC) formulation, EVITOTM 480 SC 

Fungicide (EPA Registration No. 66330-64), containing 40.3% fluoxastrobin and 59.7% inerts, 

and containing 4 lbs fluoxastrobin per gallon. Postemergence broadcast foliar applications can 

be applied using ground, aerial, or chemigation equipment. For field corn/sweet corn grown for 

seed, two foliar applications can be made at the 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 applications 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. The restricted entry interval (REI) is 12 hours. 

For the registered use on peanuts, four broadcast foliar applications of EVITOTM 480 SC 

Fungicide can be made at the rate of 0.18 lb ai/A/application for a maximum seasonal application 

rate of 0.72 lb ai/A, with a14-day PHI. The applications can be made with ground or aerial 

equipment. 

For the registered turf use, DISARMTM G Fungicide (EPA Reg. No. 66330-380) is applied a 

maximum of 4 times per season, at a maximum application rate of 0.5 lb ai/A/application with a 

minimum 14-day application interval and a maximum 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, institutional, public, commercial, and industrial buildings, parks, 

recreational areas and athletic fields) 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 cranked 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 fungal diseases in established turf. Optimum application timing for 

control of seedling diseases is just prior to, during, or after seeding. The label specifies use of 

the shortest specified application interval and/or the higher specified rate when prolonged disease 

conditions exist. 

Registered agricultural crops are peanut, tuberous and corm vegetable subgroup 1C, leaf petiole 

vegetables subgroup 4B, fruiting vegetables group 8, and turf (DP#292422, S. Winfield, 1/24/05) 

and field corn, soybeans, and the low-growing 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 corn/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 date 4/24/09) are presented in Table 2.1. 

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

Applic. 

Timing, Type, 

and Equip. 

Formulation1 

[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 Corn2 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, Bluegrass, 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 applications of the product before 

alternating to a fungicide with a different mode 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 label 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 are to be made through sprinkler-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 garlic), leafy greens subgroup (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, and 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 applications; 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, and straw were harvested after two applications. The proposed 

use directions should be revised to include the following statement: Make no more than one 

application prior to harvest of wheat forage. 

Spray adjuvants were not used in the sweet corn field trials, and a nonionic 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. HED has concluded that spray adjuvant use must be 

prohibited on product labels when the field trials did not include adjuvants (see minutes of 

4/16/08 Chemistry Science Advisory Council (ChemSAC) meeting); in additional field trials 

which HED is requesting, HED is requesting use 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

CH3

Empirical Formula C21H16ClFN4 O5 

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 (1E)-[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 physicochemical 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 (Seed Piece), Peanut and Turf, DP#292422, S. Winfield, 01/24/05. 

A detailed hazard characterization for fluoxastrobin is presented in a previous risk assessment 

(DP#292422, S. Winfield, 1/24/05). The available toxicity 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, metabolism, 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 strobilurins consists of interaction with the 

ubiquinone binding site of the mitochondrial bc1 complex (complex III) in fungal cells, thereby 

preventing the oxidation of ubihydroquinone and the transfer of electrons to cytochrome c. 

Interrupting the electron transport 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 concentration gradients and the inhibition of nucleic acid 

and protein biosynthesis. Fungal spore germination, 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 absorption value for the main study was 2.31%. 

Absorption, distribution, and metabolism were fully characterized in several rat metabolism 

studies using three 14C-radiolabeled rings in fluoxastrobin. Fluoxastrobin was extensively 

metabolized. 

Page 18 of 64 
3.1.1.2 Sufficiency of studies/data 

The submitted studies are of good quality and provide 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 requirements 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 chemical directly targets the immune 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 sheep red blood cells (SRBC) at doses as high as 

2383 mg/kg/day. However, this study has many deficiencies including uncertainty in dietary test 

material intake, and the study is classified as unacceptable. At this time, HED does not believe 

that conducting a new functional immunotoxicity study will result in a lower NOAEL than the 

regulatory dose for risk assessment, and an additional factor for database uncertainty (UFDB) is 

not needed to account for lack of this study. However, the registrant should upgrade the study to 

meet the data requirement. 

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

for fluoxastrobin was assessed using an oral toxicity study. The Agency sought expert advice 

and input on issues related to this route to route extrapolation approach (i.e. the use of oral 

toxicity studies for inhalation risk assessment) from its Federal Insecticide, Fungicide, and 

Rodenticide Act Scientific Advisory Panel (SAP) in December 2009. The Agency received the 

SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). 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 inhalation risk assessments, including 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 fluoxastrobin 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 irritant (Toxicity Category III), but is neither a dermal irritant 

nor a skin sensitizer. The acute toxicity 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 feeding dog studies, there was 

liver toxicity in the form of cholestasis as evidenced by hepatocytomegaly and cytoplasmic 

granular changes associated with increased liver 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 reduced 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 other studies but the toxicological relevance of liver 

findings in species other than the dog is questionable. For instance, among the changes were 

increased liver weight in the mouse and rat with hypertrophy and cytoplasmic changes in the 

mouse. However, there were no increases in any of the serum 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 histopathology findings in kidneys, urinary bladder, 

and urethra including the presence of calculi in the urethra 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 changes were also seen in a 90-day 

mouse feeding study with increased kidney weights and tubular hypertrophy in females. 

Following 90-day administration in dogs, there 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 cortex. In another 30-day rat feeding 

study, adrenal cortical cytomegaly with fine vacuolization was seen in all high dose males and 

the responses were comparable between the groups treated with the pure fluoxastrobin E- or 2:1 

E/Z-isomers. The adrenal changes are not likely to be endocrine related effects. 

In the rat and rabbit developmental toxicity studies and the two-generation reproduction rat 

study, there was no increased susceptibility to prenatal or postnatal exposure to fluoxastrobin and 

no effects on reproduction. 

Fluoxastrobin is not acutely neurotoxic 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/carcinogenicity, two-generation reproduction, and developmental toxicity were 

tested to or above the limit dose with no indication 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/behavior, gait characteristics, 

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, there was no difference between the control and treated animals in 

spleen cell count, macrophage activities after PMA stimulation and plaque-forming cell assay 

after challenge with sheep erythrocytes. Slight decreases were noted in IgG concentration in the 

high dose males but not females. An unacceptable 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 negative in a battery of genotoxicity tests. 

Page 20 of 64 
The carcinogenic potential of fluoxastrobin was adequately tested in rats and mice of both sexes. 

The results demonstrated a lack of treatment-related increase in tumor incidence in rats or mice. 

There was no mutagenicity concern and no structure activity relationship alert. It was concluded 

that there was no incidence of carcinogenicity 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 evaluated the quality of the toxicology and exposure 

data and has determined that it is safe for infants and children to continue 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 database for fluoxastrobin is complete for FQPA safety evaluation 

and toxicity endpoint and points of departure evaluation. However, under the new rule 

for registration, an immunotoxicity study is required. There is an immunotoxicity study; 

however, this study has many deficiencies including uncertainty in dietary test material 

intake, and the study is classified as unacceptable. At this time, HED does not believe 

that conducting a new functional immunotoxicity study will result in a lower NOAEL 

than the regulatory dose for risk assessment, and an additional factor for database 

uncertainty (UFDB) is not needed to account for lack of this study. 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 two-generation reproduction 

study in the rat. The data provide no indication of increased susceptibility of rats or 

rabbits to pre- and post-natal exposure to fluoxastrobin 

3. There is no indication in the toxicity data which include acute and subchronic 

neurotoxicity studies that fluoxastrobin is a neurotoxic chemical. 

4. The exposure databases are complete or are estimated based on data that reasonably 

account for potential exposures. The dietary food exposure assessment was performed 

based on 100% CT and tolerance-level residues. 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 incidental 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 assessment 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 Aggregate 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 inhalation 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 carcinogenic 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 endpoints for human health risk assessment are 

presented below in two separate tables: 1) Dietary and Non-Occupational exposures in Table 

3.6.1; and 2) Occupational exposures in Table 3.6.2. 

Page 22 of 64 
Table 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 

UFA= 10x 

UFH= 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 

UFA= 10x 

UFH= 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 

UFA= 10x 

UFH= 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 64 
Table 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 

UFA= 10x 

UFH= 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 

UFA= 10x 

UFH= 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 

UFA= 10x 

UFH= 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 

UFA= 10x 

UFH= 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 point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). 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 64 
Table 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 

UFA= 10x 

UFH= 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 

UFA= 10x 

UFH= 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 point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). MOE = margin of exposure. LOC = level of 

concern. 

3.7 Endocrine disruption 

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor 

Screening Program (EDSP) to determine whether certain substances (including pesticide active 

and other ingredients) may have an effect in humans or wildlife similar 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 approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

Page 25 of 64 
testing is designed to identify any adverse endocrine related effects caused by the substance, and 

establish a quantitative relationship between 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 pesticide active ingredients and 9 inert ingredients. 

This list of chemicals was selected based on the potential for human exposure through pathways 

such as food and water, residential activity, and certain post-application agricultural scenarios. 

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

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

screened under the EDSP. Under FFDCA sec. 408(p), the Agency must screen all pesticide 

chemicals. Accordingly, EPA anticipates issuing 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 pesticide active ingredient. 

For further information on the status of the EDSP, the policies and procedures, the list of 67 

chemicals, the test guidelines and the Tier 1 screening battery, please visit our website: 

http://www.epa.gov/endo/.

4.0 Dietary Exposure/Risk Characterization 

References: 

Fluoxastrobin. Petition for the Establishment of Permanent 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 Permanent 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 Permanent 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 corn/sweet corn grown for seed, wheat, and peanuts 

is adequately defined. The metabolism data on wheat, 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, turnip, 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 crops 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-dioxazine. The ratio of 

E:Z-isomer in fluoxastrobin identified in rotational crop matrices ranged from 98:2 to 74:26. 

Based upon the submitted studies, the residues of concern for rotational crops for risk assessment 

and tolerance setting purposes are fluoxastrobin and its Z-isomer. 

The confined rotational crop studies 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 poultry 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 plants, and metabolites consisting 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 tolerance 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 monitored two mass ion transitions, m/z 459→427 and 

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

commodities. 

Page 27 of 64 
Data collection methods: The data collection methods [HPLC/MS/MS method 00668, 

LC/MS/MS method 00604, and a method based 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 commodities. The method LOQs for fluoxastrobin (E + 

Z isomers) and HEC 7154 are 0.01 ppm for each analyte 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 Test 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 potentially lead to fluoxastrobin in drinking water. Although foliar 

interception may reduce the amount of fluoxastrobin available 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 followed 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 numbered as ring 1 (chlorophenyl ring), ring 2 

(pyrimidine ring), ring 3 (methoxyiminotolyl ring), and ring 4 (dioxazine ring). 

Fluoxastrobin was extensively metabolized in the rat as evidenced by the extensive metabolic 

profiles from urine, feces, and bile, and the relative absence of parent compound (except in the 

feces of rats given the high dose). The urinary metabolites were primarily the result of cleavage 

between rings 2 and 3 of the parent compound. Biliary metabolites were primarily products 

resulting from cleavage of rings 2, 3, and 4, and subsequent hydroxylation, methoxylation, and 

conjugation with glucuronic acid. HEC5725-E-des-chlorophenyl and 

HEC5725-des-chlorophenyl-dioxazine-OH were the major metabolites 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 several dioxazine phenyl two ring metabolites) 

and laying hen (e.g., several glucuronide conjugates of HEC5725- including mono- and 

di-OH-GA, and oxime-GA in addition to mono- and bi-ring fragments including 

dioxazine-oxime, 2-cyanophenol, 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 metabolic route of fluoxastrobin in rotated crop 

matrices was hydroxylation, especially at the 4-position of the chlorophenyl moiety to yield 

HEC5725-E-4-hydroxyphenyl; conjugates of this metabolite were also observed. A second 

important metabolic route was cleavage 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 parent compound was a minor metabolic route in 

rotational crops. Another minor metabolic route was hydroxylation of the parent compound in 

the dioxazine ring, followed by oxidative cleavage and hydrolysis. 

Fluoxastrobin was extensively metabolized in goats and hens, as evidenced by the extensive 

metabolic profiles and relative absence of parent compound, except in goat and poultry fat where 

a significant portion of the residue 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 appears 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 containing 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 phenyl 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 studies on representative livestock, primary crops, 

and rotational crops were also identified in rat metabolism studies; therefore, their potential toxic 

effects are assumed to have been taken into account in the toxicity studies. Fluoxastrobin was 

extensively metabolized in livestock and the 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 using 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 analytical 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 plant-back intervals and/or tolerances for 

residues in rotational crops based upon a 30-day plant-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% TRR), 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-hydroxypyrimidine metabolite [6-(2-chlorophenoxy)-

5-fluoro-4-pyrimidinol] are present 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 than the fluoxastrobin. However, the phenoxyhydroxypyrimidine metabolite residue levels in tissues 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 tolerances for residues in/on livestock commodities 

determines residues of fluoxastrobin, its Z-isomer, and its phenoxy-hydroxypyrimidine 

metabolite. Residues of fluoxastrobin and its Z-isomer 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. However, HEC5725-carboxylic acid was 

not detected in the field studies and HEC5725-E-des-chlorophenyl was detected at minor levels 

(<10% of applied radioactivity). The Z-isomer of fluoxastrobin was detected 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 concentration for fluoxastrobin (33 ppb; 1-in-10 year 

annual mean) was calculated based on the use on turf (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 Surface Water and Ground Water 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 (Screening 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 activity 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 Residue Data from Crop Field Trials with Fluoxastrobin. 

Residue Levels (ppm)1 Crop matrix Total Applic. 

Rate 

 (lb ai/A) 

PHI 

(days) n Min. Max. HAFT2 Median Mean Std. 

Dev. 

Sweet Corn (proposed use = 0.48 lb ai/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 revised as specified in OPPTS 860.1200. Samples were analyzed for 

residues of fluoxastrobin and its Z-isomer using acceptable methods, and the studies are 

supported by adequate storage stability data. However, the number and locations of the field 

trials are not in accordance with OPPTS 860.1500 for either sweet corn or wheat. For sweet 

corn, two additional sweet corn field trials must be conducted in Zones 1 (1 trial) and 5 (1 trial). 

For wheat, two additional wheat field trials must be conducted in Zone 8. Although additional 

field trials are required, HED considers 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, hay, grain, and straw, 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 detectable residues in 

peanut nutmeats and wheat grain. Samples were analyzed for residues of fluoxastrobin and its Zisomer using acceptable methods, and the wheat study is supported by adequate storage stability 

data; the available storage stability data on peanut nutmeat are adequate and can be used to 

support the peanut processed commodities due to the nature of the 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 tolerance for peanut of 0.010 

ppm, a tolerance of 0.02 ppm must be proposed for peanut. 

The data from the current peanut processing study 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 between 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 continue 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, refined oil would be 0.06 

ppm; therefore, the tolerance for peanut, refined oil must be increased to 0.06 ppm. 

The data from the wheat processing study indicate that residues of fluoxastrobin and its Z-isomer 

are unlikely to concentrate in wheat flour, middlings, shorts, or germ, but do concentrate in AGF 

(518x) and concentrate slightly in wheat bran (1.3x). 

Page 33 of 64 
Based on the HAFT for wheat grain of 0.11 ppm and the 1.3x concentration 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 tolerance for wheat bran should be established at 0.15 

ppm. For AGF, based on the 0.11-ppm HAFT and the 518x concentration factor, a tolerance of 

60 ppm should be proposed. 

Field Accumulation in Rotational Crops

Adequate field rotational crop data are available, including a limited field rotational crop study 

and an extensive field rotational crop study. 

The limited field rotational crop study was conducted 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 crop 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 support the proposed 30-day PBI for root and tuber 

vegetables, bulb vegetables, leafy vegetables, and Brassica. 

Based on the results of the limited field rotational 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 rotated 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; grass forage at 0.10 ppm; grass hay at 0.50 ppm; 

and foliage of legume vegetable, group 7, at 0.05 ppm. The data indicated that a tolerance for 

residues in/on legume vegetables, crop group 6, was not needed. In addition, the following 

rotational crop restrictions were included on the master label (EPA Registration No. 66330-64): 

“Treated areas may be replanted immediately following harvest with any crop listed on this 

label. In addition, areas may be replanted with root vegetables subgroup (e.g., carrot, radish, 

sugar beet, turnips), bulb vegetables (e.g., onion and garlic), leafy greens 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 interval. For all other crops, do not plant back within one year of 

the last field application.” 

The field rotational crop data are adequate to support the established rotational crop restrictions 

on the master label (EPA Registration No. 66330-64) and 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 feedstuffs associated with registered uses including 

field corn. The dietary burdens were calculated using HED’s June 2008 Table 1 Feedstuffs and 

guidance on constructing maximum reasonably balanced diets (MRBD). The calculated dietary 

burdens of fluoxastrobin are estimated at 6.5 and 16.6 ppm for beef and dairy cattle, and 0.093 

and 0.090 ppm for poultry and swine, respectively. 

The available ruminant feeding study is adequate to support the proposed uses. The feeding 

study data and dietary burden calculations indicate that the established 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 swine 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 study 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 established Codex or Canadian maximum 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 attributable to a single dose. An aRfD was not 

established. 

4.2.2 Chronic Dietary Exposure/Risk 

A chronic dietary (food and drinking 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. The assumptions of this dietary assessment 

included tolerance level residues and 100% crop treated (CT). Based on processing studies, the 

processing factors for tomato puree, potato chips, dry potato (granules/flakes), and potato flour 

were reduced to 1. Separate tolerances were set for peanut oil, wheat bran and tomato paste; 

therefore, the processing factors for these commodities 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 dietary 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 subgroups. The dietary (food and drinking water) 

exposure is estimated at 19% of the chronic Population Adjusted Dose (cPAD) for the general 

U.S. population and 42% of the cPAD for children 1-2 yrs, the population subgroup with the 

highest estimated chronic dietary exposure to fluoxastrobin. 

 

Table 4.2.2. Result of Chronic Dietary 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 carcinogenic 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 flour, 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 set 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) for Fluoxastrobin Dietary 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 application to turf, the 

use on turf results in residential handler exposure. Residential handlers may be exposed from 

loading and applying granular fluoxastrobin for spot treatment and/or broadcast control of 

diseases on turf. Loading/applying with a push 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 short-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 estimated dermal and inhalation exposures were 

compared to the oral No Observed Adverse Effect Level (NOAEL) of 3.0 mg/kg/day from a 90-

day subchronic feeding dog study. Calculation inputs and results 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 the endpoints and point of departures were the 

same for both scenarios. Short-term inhalation risks were not of concern to HED. Intermediateterm dermal, inhalation, and combined (intermediate-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 Flu

Exposure Scenario Crop or Target App Rate (lb ai/A)1 Acres Treated Daily2

Dermal 

Unit 

Exposure 

(mg/lb 

ai)3

Inhalation 

Unit 

Exposure 

(ug/lb ai)4

Intermediate 

Term 

Baseline 

Dermal 

Dose 

(mg/kg/day)5

Short- and 

IntermediateTerm Baseline 

Inhalation 

Dose6

Combined 

Daily 

Dose7

MOE 

IntermediateTerm 

Dermal8 

M

Int

In

Loader/Applicator 

Loading/Applying Granulars via 

Push Type Spreader (ORETF) Turf 0.5 0.5 0.67 0.00088 0.0000055 0.00000031 0.0000058 550,000 9

Loading/Applying Granulars via 

Belly Grinder or Similar (PHED) Turf 0.5 0.5 10 0.062 0.000904 0.000022 0.00093 3,300 

1 Application rate is based on maximum values found in proposed label (EPA Reg. No. 66330-380).2 Area treated is based on the area that can be reasonably treated in a single day based on the application method (standard EPA/OPP/HED values).3 Dermal Unit Exposure PHED Baseline represents long pants, long sleeved shirts, no gloves, open mixing/loading. ORETF Baseline Dermal Exposure represents long pants and 4 PHED Baseline Inhalation Exposure represents no respiratory protection, open mixing/loading. ORETF Baseline Inhalation Exposure represents no respiratory protection, open 5 Dermal 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/1000 ug)conversation*Application Rate*Area Treated)/body weight (70kg)7 Combined Daily Dose= Baseline Dermal Dose + Baseline Inhalation Dose8 MOE Baseline Dermal = NOAEL (3.0 mg/kg/day)/Dermal Dose9 MOE Baseline Inhalation = NOAEL (3.0 mg/kg/day)/Inhalation Dose10 Combined 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 could 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 available were used in the fluoxastrobin residential 

assessment. Since chemical-specific data were unavailable, the Agency used the current 

approaches for residential assessment, many of which include recent upgrades to the SOPs. For 

example, for the hand-to-mouth calculations for children (three to less than six years old), a 5% 

transferability factor was applied 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 conservative, 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 input parameter have not been used in the calculations. Maximum 

application rates have been used for all scenarios. 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 should 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 used for all dermal risk estimates, even though the residential 

exposure duration is believed to be mostly short-term based on the use pattern. 

Based on the Agency's current practices, a quantitative 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 pesticide applications. The Agency 

sought expert advice and input on issues related to volatilization of pesticides from its Federal 

Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009. 

The Agency received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). 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, the way to incorporate postapplication inhalation 

exposure into the Agency's risk assessments. If new policies or procedures are put into place, the 

Agency may revisit the need for a quantitative postapplication 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 routes of exposure include 

dermal (adults and children) and incidental oral ingestion (children [three to less than six years 

old] only). Since no acute hazard has been identified, an assessment of episodic granular 

ingestion was not conducted. While it is assumed that most residential use will result in 

short-term (1 to 30 days) postapplication exposures, it is also believed that intermediate-term 

exposures (> 30 days to 180 days) are possible, albeit unlikely. 

Page 39 of 64 
Page 40 of 64 

The highest use rate was chosen for the assessment (i.e., 0.5 lb ai/A). A summary of the 

estimated exposures and risks, along with the algorithms 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) 

Subgroup 

exposed 

Activity Application 

Rate 

 (lb ai/A) 

Fraction 

of ai 

Available 

Turf Transferrable 

Residue at Day “0" 

(μg/cm2)1

Dermal 

Transfer 

Coefficient 

(cm2/hr)

Exposure 

Time 

(hrs/day) 

Dermal 

Absorption 

Factor 

Body 

Weight 

(kg) 

Adult Mowing turf 4 0.5 0.05 0.280 3,400 2 2.3% 70 Adult Golf Course Reentry 0.5 0.05 0.280 500 4 2.3% 70 Adult High Contact 0.5 0.05 0.280 14,500 2 2.3% 70 Children High Contact 0.5 0.05 0.280 5,200 2 2.3% 15 

1 Turf Transferrable Residue (μg/cm2) = Application rate (lb ai/A) x Fraction of ai Available x 4.54E+8 μg/lb x 2.47E-8 A/cm2 

2 Daily Dose = (Turf Transferrable Residue x 1E-3 mg/μg x Dermal Transfer Coefficient x Dermal Absorption Factor x Exposure Time)/Body weight 

3 Intermediate-Term Dermal MOE = Intermediate-Term Oral NOAEL (3 mg/kg/day) /Daily Dose 4 Transfer Coefficient from K. Lowe (February 2009): Revised Mesotrione: Occupational and Residential Exposure/Risk Assessment for the New Use on Turf in Comm

Because this transfer coefficient is usually applied to occupational mowing of turf and golf courses, this estimate is considered extremely conservative for residential extransfer coefficients from contact with treated turf are short-term estimates, while intermediate-term dermal endpoints were used because of the lack of a short-term dermpost-application risk estimates are considered extremely conservative. 

Table 5.2.1.2. Oral Hand-to-mouth Exposure and Risk for Children from Treated Lawns (Short- and Intermediate-Term) 

Exposure Duration Application 

Rate 

 (lb ai/A) 

Fraction of 

ai Available 

Turf 

Transferrable 

Residue at Day 

“0" (μg/cm2)1

Exposure 

Time 

(hrs/day) 

Extraction by saliva 

Hand Surface Area (cm2/event) 

Frequency 

(events/ hr) 

Body 

Weight 

(kg) 

Short-Term 0.5 0.05 0.28 2 0.5 20 20 15 

Intermediate-Term 0.5 0.05 0.28 2 0.5 20 9.5 15 

1Turf Transferrable Residue (μg/cm2) = Application rate (lb ai/A) x Fraction of ai Available x 4.54E+8 μg/lb x 2.47E-8 A/cm22 Daily 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)] / [3 MOE = Oral NOAEL (3 mg/kg/day) /Daily Dose 

Table 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 ai 

Available 

Grass Residue at Day “0" 

(μg/cm2)1

Surface Area Mouthed 

(cm2/day) 

Body Weight 

(kg) 

 Daily Dose2

(mg/kg/day) 

0.5 0.2 1.1 25 15 0.0019 

1Grass Residue (μg/cm2) = Application rate (lb ai/A) x Fraction of ai Available x 4.54E+8 μg/lb x 2.47E-8 A/cm22 Daily Dose = [Grass residue (μg/cm2) x Surface Area Mouthed (cm2/day) x 1E-3 mg/μg] / [Body Weight (kg)] 3 Short- / Intermediate-Term Oral MOE = Short- / Intermediate-Term Oral NOAEL (3 mg/kg/day) /Daily Dose 

Page 41 of 64 
Page 42 of 64 

Table 5.2.1.4. Exposure and Risk for Children from Ingestion of Soil from Treated Lawns (Short- and Intermediate-Term) 

Application Rate 

 (lb ai/A) 

Fraction of ai 

Available 

Soil Residue at Day “0" 

(μg/g)1

Ingestion Rate 

(mg/day) 

Body Weight 

(kg) 

 Daily Dose2

(mg/kg/day) 

0.5 1 3.8 100 15 0.000025 

1 Soil residue (μg/g) = [Application Rate (lbs ai/A) x Fraction of ai Available x 4.54E+8 μg/lb x 2.47E-8 A/cm2 x 0.67 cm3/g soil] 2 Daily Dose = [Soil residue (μg/g) x Ingestion rate (mg/day) x 1E-6 g/μg] / [Body Weight (kg)] 3 MOE = Oral NOAEL (3 mg/kg/day) /Daily Dose 
Page 43 of 64 

The MOEs for residential postapplication exposure to fluoxastrobin are all above 100, and 

therefore, do not exceed HED's level of concern. 

HED combines risk values resulting from separate 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 postapplication exposure to children, HED generally combines the 

dermal and incidental oral (hand to mouth) exposures, but does not include 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 estimate of oral postapplication exposure. For the 

proposed turf uses of fluoxastrobin, the total (dermal + incidental oral) postapplication MOE for 

children resulted in an MOE 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 Postapplication Exposure and Risk Estimates from Treated Lawns 

 Daily Dose1

(mg/kg/day) MOE2 Combined MOE3

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*Application Rate*Area treated)/body weight 

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

3. For children, total MOE = NOAEL (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 are expected to be similar to, or in many cases less than, those 

evaluated in section 5.2.1 Home Uses; therefore, a separate recreational exposure assessment 

was not included. Additionally, golf course exposures and risks were already assessed. 

5.3 Spray Drift

Spray drift is always a potential source of exposure to residents nearby to spraying operations. 

This is particularly the case with aerial application, but to a lesser extent, could also be a 

potential source of exposure from the ground application methods additionally employed for 

fluoxastrobin. The Agency has been working with the Spray Drift Task Force, EPA Regional 

Offices, and State Lead Agencies for pesticide regulation and other parties to develop the best 
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 Spray Drift Task Force, a membership of U.S. 

pesticide registrants, and is developing a policy on how to appropriately apply the data and the 

AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast 

and ground hydraulic methods. After the policy is in place, the Agency may impose further 

refinements in spray drift management practices to reduce off-target drift and risks associated 

with aerial as well as other application types where appropriate. 

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 application rates, this scenario is protective of any exposure of 

farm children via spray drift from agricultural 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 the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure. For fluoxastrobin, potential exposures from food, drinking water, and 

residential scenarios were aggregated. 

6.1 Acute Aggregate Risk

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

not identified. 

6.2.1 Short-Term and Intermediate-Term Aggregate Risk

There is potential short- and intermediate-term exposure to fluoxastrobin via the dietary (which 

is considered background exposure) and residential (which is considered primary) pathways. For 

adults, these pathways lead to exposure via the 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) LOC1

Max 

Allowable 

Exposure2

(mg/kg/day)

Average 

Food & 

Water 

Exposure3 

(mg/kg/day)

Residential 

Exposure4

(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 years 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 carcinogenic to humans;” therefore, an aggregate 

cancer assessment was not conducted. 

7.0 Cumulative Risk Characterization/Assessment 

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to fluoxastrobin and any other substances 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 toxicity with other 

substances. For information regarding EPA's efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA's Office of Pesticide Programs concerning common 

mechanism determinations and procedures for cumulating effects from substances found to have 

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

8.0 Occupational Exposure/Risk Pathway 

Reference: 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. 

8.1 Short- and Intermediate-Term Handler Risk 

Fluoxastrobin can be applied to sweet corn, field corn/sweet corn grown for seed, and wheat 

using aerial, chemigation, and groundboom application equipment. Handler exposure is 

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

Chemical-specific data for assessing exposure during pesticide 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-specific data are not available (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 application in a male monkey, absorption was negligible 

(1.16% preliminary, 2.16% main). The normalized absorption value for the main study (MRID 

45911502) was 2.31%. Therefore, HED set the dermal absorption value at 2.3% for risk 

assessment purposes. 

Since the short- and intermediate-term inhalation endpoint was based on an oral study (90-day 

subchronic feeding study in the dog), and 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 handlers are included in Table 8.1. The maximum 

application rate for each exposure scenario is presented as the worst-case scenario. All handler 

scenarios resulted in MOEs greater than the level of concern (i.e., an MOE = 100) at some level 

of risk mitigation. 
Page 47 of 64 

Dermal 

The proposed label proposes baseline 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 baseline 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 concentrates to support aerial applications to sweet corn, 

field/sweet corn grown for seed, and wheat; and 

• mixing/loading liquid concentrates to support chemigation applications to sweet corn, 

field/sweet corn grown for seed, and wheat. 

Only engineering control (enclosed cockpit) data are available to assess intermediate-term 

dermal risks to handlers operating 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 risks 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 operating aircraft. The short- and intermediate-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 intermediate-term inhalation risks do not exceed 

HED’s level of concern, provided personal protective equipment listed for intermediate-term 

dermal risks are worn (see Dermal above). 
Page 48 of 64 

Table 8.1. Agricultural Handler Exposure and Risk for Fluoxastrobin

Unit Exposurec,d,e Dosef,g (mg/kg/day) MO

Exposure 

Scenario 

Crop or 

Target 

App 

Ratea

(lb 

ai/A) 

Acres 

Treated 

Dailyb

IntermediateTerm 

Baseline 

Dermal 

(mg/lb ai) 

IntermediateTerm 

PPE-G 

Dermal 

(mg/lb ai) 

Short- & 

IntermediateTerm 

Baseline 

Inhalation 

(μg/lb ai) 

Baseline 

Dermald,h

PPE-G 

Dermali

Baseline 

Inhalatione

Baseline 

Dermalf

PPE-G 

Dermal 

Baseli

Inhalati

Mixer/Loader 

Wheat 0.12 1,200 2.9 0.023 1.2 0.14 0.0011 0.0025 22 2,800 1,200 

Sweet corn 0.12 350 2.9 0.023 1.2 0.04 0.00032 0.00072 75 9,500 4,200 

Mixing/Loading 

Liquid 

Concentrates 

for Aerial 

Applications Field/Sweet 

corn grown 

for seed 

0.18 350 2.9 0.023 1.2 0.06 0.00048 0.0011 50 6,300 2,800 

Field/Sweet 

corn grown 

for seed 

0.18 350 2.9 0.023 1.2 0.06 0.00048 0.0011 50 6,300 2,800 

Mixing/Loading 

Liquid 

Concentrates 

for 

Chemigation 

Applications 

Sweet corn 

and Wheat 0.12 350 2.9 0.023 1.2 0.04 0.00032 0.00072 75 9,500 4,200 

Wheat 0.12 200 2.9 0.023 1.2 0.023 0.00018 0.00041 130 17,000 7,300 

Sweet corn 0.12 80 2.9 0.023 1.2 0.0091 0.000073 0.00016 330 41,000 18,00

Mixing/Loading 

Liquids 

Concentrates 

for 

Groundboom 

Applications 

Field/Sweet 

corn grown 

for seed 

0.18 80 2.9 0.023 1.2 0.014 0.00011 0.00025 220 28,000 12,00

Applicator 

Applying 

Sprays via 

Aerial 

Wheat 0.12 1,200 0.005 (eng. control) No Data 0.068 (eng. control) 0.00024 (eng. control) No Data 0.00014 (eng. control) 13,000 (eng. control) No Data 21,00

(eng

contro
Page 49 of 64 

Table 8.1. Agricultural Handler Exposure and Risk for Fluoxastrobin

Unit Exposurec,d,e Dosef,g (mg/kg/day) MO

Exposure 

Scenario 

Crop or 

Target 

App 

Ratea

(lb 

ai/A) 

Acres 

Treated 

Dailyb

IntermediateTerm 

Baseline 

Dermal 

(mg/lb ai) 

IntermediateTerm 

PPE-G 

Dermal 

(mg/lb ai) 

Short- & 

IntermediateTerm 

Baseline 

Inhalation 

(μg/lb ai) 

Baseline 

Dermald,h

PPE-G 

Dermali

Baseline 

Inhalatione

Baseline 

Dermalf

PPE-G 

Dermal 

Baseli

Inhalati

Equipment 

Sweet corn 0.12 350 0.005 (eng. control) No Data 0.068 (eng. control) 0.000069 (eng. control) No Data 0.000041 (eng. control) 43,000 (eng. control) No Data 74,00

(eng

contro

Applying 

Sprays via 

Aerial 

Equipment 

(continued) 

Field/Sweet 

corn grown 

for seed 

0.18 350 0.005 (eng. control) No Data 0.068 (eng. control) 0.0001 (eng. control) No Data 0.000061 (eng. control) 29,000 (eng. control) No Data 49,00

(eng

contro

Wheat 0.12 200 0.014 0.014 0.74 0.00011 0.00011 0.00025 27,000 27,000 12,00

Sweet corn 0.12 80 0.014 0.014 0.74 0.000044 0.000044 0.0001 68,000 68,000 30,00

Applying 

Sprays via 

Groundboom 

Equipment Field/Sweet 

corn grown 

for seed 

0.18 80 0.014 0.014 0.74 0.000066 0.000066 0.00015 45,000 45,000 20,00

Flagger 

Sweet corn 

and Wheat 0.12 350 0.011 Not applicable 0.35 0.00015 Not applicable 0.00021 20,000 Not applicable 14,00

Flagging for 

Aerial Sprays 

Applications 

Field/Sweet 

corn grown 

for seed 

0.18 350 0.011 Not applicable 0.35 0.00023 Not applicable 0.00032 13,000 Not applicable 9,500 

a. Application Rates based on proposed uses on label for fluoxastrobin product Fluoxastrobin 480 SC Fungicide (EPA Reg. 66330-64). b. Science Advisory Council Policy # 9.1 c. 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 treated x inhalation absorption (100%) / body weight (70 kg adult). 

h. Dermal MOE = NOAEL (3.0 mg/kg/day) / dermal daily dose (mg/kg/day). Level of concern = 100. 
Page 50 of 64 

i. 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 Dermal MOE) + (1/Baseline Inhalation MOE). Those risks specified as engineering control represent en
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 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 pesticide applications. The Agency 

sought expert advice and input on issues related to volatilization of pesticides from its Federal 

Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009. 

The Agency received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). 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, the way to incorporate postapplication inhalation 

exposure into the Agency's risk assessments. If new policies or procedures are put into place, the 

Agency may revisit the need for a quantitative postapplication 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 postapplication risks were assessed. 

There were no chemical-specific dislodgeable foliar residue (DFR) data to assess postapplication 

risks to workers while performing tasks related to crops treated with fluoxastrobin. Occupational 

postapplication exposures and risks were assessed using HED’s default assumptions that 20 

percent of the initial application is available for transfer on day 0 (i.e., 12 hours after application) 

and that the residue dissipates at a rate of 10 percent per day. 

HED uses a concept known as the transfer coefficient to numerically represent the 

postapplication exposures one would receive (generally presented as cm2

/hour). A transfer 

coefficient is a measure of the residue transferred from a treated surface to a person who is doing 

a task or activity in a treated area. These values are the ratio of an exposure for a given task or 

activity to the amount of pesticide residue on treated surfaces available for transfer. HED has 

developed a series of standard transfer coefficients that are unique for a variety of job tasks or 

activities that are used in lieu of chemical- and scenario-specific data. HED used Policy 003.1 

Science Advisory Council for Exposure Policy Regarding Agricultural Transfer Coefficients to 

estimate transfer coefficients for the various tasks that 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 noncancer postapplication risk assessment were 

short-term and intermediate-term. However, since there is no dermal toxicological 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/cm2) x TC (cm2/hr) x Hr/Day) x DA / 1,000 (μg/mg) 

Where: 

DE(t) = Dermal exposure or amount deposited on the surface of the skin at time (t) 

attributable for activity in a previously treated area, 

 DFR(t) = Dislodgeable foliar residue at time “t” (μg/cm2), 

 TC = Transfer Coefficient (cm2

/hour), 

 Hr/day = Exposure duration meant to represent a typical workday (8 hours), and 

 DA = Dermal absorption factor (0.023) 

Where: 

 Default DFR (μg/cm2

) = AR (lb ai/A) x F x (1- D)t x CF1 x CF2 

 AR = Maximum application rate, 

 F = Fraction of ai retained on the foliage, 

 D = Fraction of residue that dissipates daily, 

 t = Postapplication day, 

 CF1 = 4.54E+8 μg/lb, and 

 CF2 = 2.47E-8 A/cm2. 

Table 8.2.1 presents the default DFR values on day 0 (12 hours after application) that were used 

for this postapplication exposure 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/cm2) 

Day after 

Application 

Default DFR

(μg/cm2)

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/cm2) = 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/cm2

. 

 

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 application) 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 Assumptions1,2,3 

Crop 

Grouping 

Application 

rate 

(lb ai/acre) 

Default 

DFR 

(μg/cm2) 

Maximum Transfer Coefficient (μg/cm2) Day after 

Application 

MOE4 

(Level of Concern

= 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 highest transfer coefficient available. 2

DE(t) (mg/day) = (DFR(t) (μg/cm2) x TC (cm2/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) for Agricultural Pesticides, active ingredients 

classified as acute Toxicity Categories III or IV for these routes are assigned a 12-hour REI. 

Therefore, the 12-hour REI that appears on the proposed label is adequate. 
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 Part 158 as a part of the data requirements 

for registration of a pesticide (food and non-food uses). 

The Immunotoxicity Test Guideline (OPPTS 870.7800) prescribes functional 

immunotoxicity testing and is designed to evaluate 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 viral infections such as tuberculosis (TB), Severe Acquired 

Respiratory Syndrome (SARS), or neoplasia. Because the immune system is highly 

complex, studies assessing functional immunotoxic endpoints are helpful in fully 

characterizing a pesticide’s potential immunotoxicity. These data will be used in 

combination with data from hematology, lymphoid organ weights, and histopathology in 

routine chronic or subchronic toxicity studies 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, reproductive, and endocrinologic toxicities. 

Additionally, the EPA has established an oral reference dose (RfD) for tributyltin oxide 

(TBTO) based on observed immunotoxicity in animal studies (IRIS, 1997). 

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

If the immunotoxicity study shows that the test material poses either a greater or a 

diminished risk than that given in the interim decision’s conclusion, the risk assessments 

for the test material may need to be revised 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 should be revised to specify a minimum PHI 

for corn stover of 23 days. 

• The proposed use directions for wheat should be revised to include the following 

statement: Make no more than one application prior to harvest of wheat forage. 

• 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. 

860.1500 Crop Field Trials

• Two additional sweet corn field trials reflecting the proposed use pattern must be 

conducted in Zones 1 and 5. 

• Two additional wheat field trials reflecting the 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, refined 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 too low; tolerances 

should be proposed at 0.15 ppm for 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 acre 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 Permanent 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 Permanent 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 Permanent 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 Data Requirements for Food Use 

Test Technical

Required Satisfied

870.1100 Acute Oral Toxicity....................................................... 

870.1200 Acute Dermal Toxicity .................................................. 

870.1300 Acute Inhalation Toxicity.............................................. 

870.2400 Primary Eye Irritation.................................................... 

870.2500 Primary Dermal Irritation .............................................. 

870.2600 Dermal Sensitization...................................................... 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

870.3100 Oral Subchronic (rodent) ............................................... 

870.3150 Oral Subchronic (nonrodent) ......................................... 

870.3200 21-Day Dermal .............................................................. 

870.3250 90-Day Dermal .............................................................. 

870.3465 90-Day Inhalation.......................................................... 

yes 

yes 

yes 

CR1 

CR1 

yes 

yes 

yes 

NR1 

NR1 

870.3700a Developmental Toxicity (rodent)................................... 

870.3700b Developmental Toxicity (nonrodent)............................. 

870.3800 Reproduction ................................................................. 

yes 

yes 

yes 

yes 

yes 

yes 

870.4100a Chronic Toxicity (rodent) .............................................. 

870.4100b Chronic Toxicity (nonrodent)........................................ 

870.4200a Oncogenicity (rat).......................................................... 

870.4200b Oncogenicity (mouse).................................................... 

870.4300 Chronic/Oncogenicity.................................................... 

- 

yes 

 - 

yes 

yes 

 - 

yes 

 - 

yes 

yes 

870.5100 Mutagenicity—Gene Mutation - bacterial..................... 

870.5300 Mutagenicity—Gene Mutation - mammalian................ 

870.5375 Mutagenicity—Structural Chromosomal Aberrations... 

870.5395 Mutagenicity—Other Genotoxic Effects....................... 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

870.6100a Acute Delayed Neurotox. (hen) ..................................... 

870.6100b 90-Day Neurotoxicity (hen)........................................... 

870.6200a Acute Neurotox. Screening Battery (rat) ....................... 

870.6200b 90-Day Neuro. Screening Battery (rat).......................... 

870.6300 Develop. Neuro.............................................................. 

 no 

 no 

 NR1 

 CR1

 no 

 - 

 - 

yes 

yes 

 - 

870.7485 General Metabolism ...................................................... 

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

870.7800 Immunotoxicity ............................................................. 

yes 

yes 

yes 

yes 

yes 

no 

Special Studies for Ocular Effects 

Acute Oral (rat)........................................................... 

Subchronic Oral (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 LD50 >2000 mg/kg III 

870.1200 Acute dermal - rat 45865613 LD50 >2000 mg/kg III 

870.1300 Acute inhalation - rat 45865618 LC50 = 4.9 mg/L IV 

870.2400 Acute eye irritation - rabbit 45865620 moderate irritant III 

870.2500 Acute dermal irritation - rabbit 45865622 not an irritant IV 

870.2600 Skin sensitization - guinea pig 45865624 not a sensitizer - 
DRAFT – INTERNAL AND DELIBERATIVE- 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); /acceptable/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) /acceptable/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 cytoplasmic 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 toxicity 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 

Maternal NOAEL = 100 mg/kg/day 

LOAEL = 400 mg/kg/day based on cold ears, transient 

body weight loss, and decreased food consumption. 

Developmental 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 F1 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 F1 and/or F2 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 increased 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/plate 

Test 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/plate 

Test 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 activated, T-cell mediated IgM 

response to SRBC. However, the study is considered 

unacceptable because of uncertainty in dietary test 

material intake, failure to report 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

(1E)-[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

CH3

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

(1Z)-[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

CH3

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 

Cl F

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 Properties 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/cm3 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, pKa no dissociation constant at pH 4-9 MRID 45865303 

Octanol/water partition coefficient, Log(POW) 2.85 (20 °C); POW = 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 pesticide or other chemical. These studies, which comprise the 

Pesticide Handler Exposure Database (PHED) and the Outdoor Residential Exposure Task Force 

(ORETF), have been determined to require a review of their ethical conduct 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 Human Studies Review Board: 

None.