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7.3 Intermediate-Term Aggregate Risk ........................................................................... 31

7.4 Chronic Aggregate Risk .............................................................................................. 31

7.5 Cancer Aggregate Risk ................................................................................................ 31

8.0 Cumulative Exposure/Risk Characterization ............................................................... 31

9.0 Occupational Exposure/Risk Characterization ............................................................ 32

9.1 Short-/Intermediate-Term Handler Risk................................................................... 32

9.2 Short-/Intermediate-Term Post-Application Risk .................................................... 33

9.2.1 Dermal Post-Application Risk................................................................................. 33

10.0 References......................................................................................................................... 34

Appendix A. Toxicology Profile................................................................................................ 36

A.1 Toxicology Data Requirements................................................................................... 36

A.2 Toxicity Profiles............................................................................................................ 37

Appendix B. Physical/Chemical Properties............................................................................. 40

Appendix C. International Residue Limit Status Sheet. ........................................................ 41

Appendix D. Review of Human Research................................................................................ 42
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1.0 Executive Summary

Azoxystrobin [methyl (2E)-2-{2-[6-(2-cyanophenoxy)pyrimidin-4-yloxy]phenyl}-3-

methoxyacrylate] is a broad spectrum fungicide used to control plant diseases on agricultural 

crops, turf and ornamentals, and to control molds and fungi on indoor surfaces. Azoxystrobin 

belongs to a class of pesticidal compounds called β-methoxyacrylates, which are derived from 

the naturally occurring strobilurins. Its biochemical mode of action is inhibition of electron 

transport. 

Syngenta Crop Protection, Inc. (Syngenta) has proposed azoxystrobin uses on ginseng (import), 

oats, and cereal grains. Concurrently, Syngenta is requesting to amend the pre-harvest intervals 

(PHIs) of the registered labels for cereals (wheat, barley, and triticale) from 14-30 days to 7 days 

for forage and hay and to remove the 45-day PHI for grain and straw and replace it with a growth 

stage restriction for the last application. The limitation is to apply the last application no later 

than Feekes Growth Stage 10.54. The most recent human health risk assessment was conducted 

to evaluate azoxystrobin use on sugarcane (K. Rury, D389702, 01/18/2012). Since the last risk 

assessment, no additional hazard data have been submitted. In accordance with the 2007 revised 

40 CFR Part 158 Toxicology data requirements, a subchronic inhalation toxicity study and an 

immunotoxicity study were required for azoxystrobin. The Agency has waived the inhalation 

toxicity study data requirement for azoxystrobin at this time (TXR# 0056307). An 

immunotoxicity study remains required for azoxystrobin. 

Use Profile

For ginseng, azoxystrobin SC (suspension concentrate) Ortiva is proposed for four foliar 

applications at 10 mL formulated product/20 mL water with a 7-day pre-harvest interval (PHI). 

The maximum application rate is 1519 g ai/ha (1.36 lb ai/A). Additional information was 

received: azoxystrobin content changed from 20% to 21.7%; application spray volume (3500 

L/ha); product rate (1750 g (ml)/ha); and single application rate (379.75 g/ha) (email 

communication Erin Malone, 10/09/12). Based on these information, the maximum seasonal 

application rate is 1519 g ai/ha (1.36 lb ai/A). 

Azoxystrobin is proposed for use as a foliar application on cereal grain crops using ground, 

aerial, and chemigation equipment. The use profile is summarized in Table 3.3. The proposed 

application rates on cereals (wheat, triticale, barley, oats, and rye) range from 0.07-0.20 lb ai/A 

or (4-12.0 fl oz product/A) with a maximum seasonal application rate of 0.40 lb ai/A for 

Abound® Flowable Concentrate and 0.03-0.13 lb ai/A or (7-14 fl oz product/A) with a 

maximum seasonal application rate of 0.13-0.26 lb ai/A for Quilt Xcel® and Quilt®. The 

Abound®, Quilt Xcel®, and Quilt® labels specify that no more than 0.40 lb ai/A of any 

azoxystrobin containing products should be applied per season and no more than 2 foliar 

applications should be applied per season. All labels require a 7-day PHI for forage and hay. 

There is a growth stage restriction for the last application to not apply later than Feekes Growth 

Stage 10.54 (BBCH 71).

In addition, Syngenta is requesting to add oats and rye use on three azoxystrobin manufacturing 

products: Azoxystrobin Manufacturing Use Concentrate (MUC) (EPA Reg. No. 100-1119), 

Azoxystrobin Dry Technical Manufacturing Use Concentrate (MUC) (EPA Reg. No. 100-1120), 
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and Azoxystrobin Millbase Manufacturing Use Product (MUP) (EPA Reg. No. 100-1220).

Toxicity/Hazard

The risk assessment for azoxystrobin is based on a well-characterized and nearly complete 

toxicology database, with the exception of an immunotoxicity study and an inhalation toxicity 

study; however, the Agency has waived the inhalation toxicity study data requirement at this 

time (TXR# 0056307). In a 21-day repeated dose dermal study in the rat, no dermal or systemic 

toxicity was seen at the limit dose. In repeat-dose oral studies, the liver and bile ducts were 

consistently the target organs of azoxystrobin toxicity. No developmental effects were seen in 

rabbit or rat developmental toxicity studies and no reproductive or offspring effects were seen in 

the 2-generation rat reproduction study. Although azoxystrobin induced a weak mutagenic 

response in the mouse lymphoma assay, the activity expressed in vitro is not expected to be 

expressed in whole animals (in vivo). Azoxystrobin is classified as “not likely to be carcinogenic 

to humans.” 

Azoxystrobin has a low order of acute toxicity via oral, dermal and inhalation routes of exposure 

as demonstrated by the toxicity categories (III & IV). Azoxystrobin is not an eye or skin irritant 

and is not a skin sensitizer. 

To account for the use of a lowest observed adverse effect level (LOAEL) from the acute 

neurotoxicity study in rats, the Agency believes that a 3X FQPA SF (Food Quality Protection 

Act (FQPA) Safety Factor (SF) (as opposed to a 10X) will be adequate to extrapolate a no 

observed adverse effect level (NOAEL) in assessing acute risk. No additional safety factor is 

needed for short-term, intermediate-term, and chronic risk assessment. Although an 

immunotoxicity study is needed to complete the toxicological database, there are no concerns for 

immunotoxicity based on the results of the existing studies. There are no indications in the 

available studies that organs associated with immune function, such as the thymus and spleen, 

are affected by azoxystrobin, and azoxystrobin does not belong to a class of chemicals that 

would be expected to be immunotoxic. The selected toxicity endpoints and PODs for risk 

assessment are based on the most sensitive and relevant data. 

Dietary Exposure (Food and Water)

The residue chemistry data and environmental fate data are adequate to assess human exposure. 

The assessments are based on reliable data and will not underestimate exposure or risk. The 

estimated drinking water concentrations (EDWCs) have not changed since the last risk 

assessment (K. Rury, D389702, 01/18/2012) from the turf application scenario (currently 

registered). The highest EDWCs for all proposed and registered were incorporated directly into 

the dietary assessment. A partially refined acute dietary assessment was conducted using 100% 

crop treated (%CT) estimates, tolerance-level residues (for all commodities except citrus fruit) 

and empirical or Dietary Exposure Evaluation Model – Food Commodity Intake Database 

(DEEM-FCID) default processing factors. The results of the acute dietary analysis for food and 

drinking water show that the acute dietary risk estimates are below the Agency’s level of concern

(LOC) (<100% of the acute population adjusted dose (aPAD)) for all population subgroups and

were estimated at 17% of the aPAD for the general U.S. population and 41% of the aPAD for the 

most highly exposed population subgroup (children 1-2 years old). A partially refined chronic 

dietary assessment was conducted using tolerance-level residues, average % CT estimates and 
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empirical or default DEEM-FCIDTM processing factors. The results of the chronic dietary 

analysis for food and drinking water indicate that the chronic dietary risk estimates are below the 

Agency’s LOC (<100% of the chronic population adjusted dose (cPAD)) for all population 

subgroups and were estimated at 7% of the cPAD for the general U.S. population and 17% of the 

cPAD for the most highly exposed population subgroup (children 1-2 years old). Azoxystrobin

is classified as “not likely to be carcinogenic to humans;” therefore, a cancer dietary risk 

assessment was not performed. 

Residential Exposure

No new residential uses were requested in this petition. However, azoxystrobin is currently 

registered for use on several residential/non-agricultural use sites. Residential exposure and risks 

from use on turf and indoor surfaces were reassessed using the updated 2012 HED Residential 

Standard Operating Procedures (SOPs). All assessed residential risk estimates resulted in 

margins of exposure (MOEs) > 100; and therefore, are not of concern to HED. 

Occupational Exposure

Based on the proposed use pattern of azoxystrobin on cereal grains, there is a potential for shortand intermediate-term occupational exposure during handling (mixing, loading, and applying) 

and post-application activities. Chronic exposure is not expected for the proposed use patterns. 

The results of the occupational handler exposure and risk assessment estimates indicate that 

short- and intermediate-term inhalation MOEs are not of concern to HED (i.e., MOEs > 100) 

with baseline mitigation. The short-term inhalation MOEs range from 38,000 to 570,000 for 

occupational handlers. The intermediate-term MOEs range from 30,000 to 460,000 for 

occupational handlers. Although occupational dermal exposure is expected following treatment 

of cereal grain crops, dermal hazard was not identified for azoxystrobin. Therefore, a 

quantitative post-application dermal risk assessment was not conducted. Based on the Agency's 

current practices, a quantitative non-cancer occupational post-application inhalation exposure 

assessment was not performed for azoxystrobin at this time. If new policies or procedures are 

put into place, the Agency may revisit the need for a quantitative occupational post-application 

inhalation exposure assessment for azoxystrobin. A chemical-specific dislodgeable foliar 

residue (DFR) study is available for the use of azoxystrobin on grapes, but has not been 

employed in this or previous risk assessments because HED determined there is no hazard via 

the dermal route. 

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 data, including studies from the 

Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1), the Agricultural Handler 

Exposure Task Force (AHETF) database, the Outdoor Residential Exposure Task Force 

(ORETF) database, and the Agricultural Re-entry Task Force (ARTF) database, are subject to 

ethics review pursuant to 40 CFR 26, have received that review, and are compliant with 

applicable ethics requirements. For certain studies, that review may have included review by the 

Human Studies Review Board. Descriptions of data sources as well as guidance on their use can 

be found at http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html.
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2.0 HED Recommendations

HED recommends that the registration request be conditionally granted for azoxystrobin use on 

ginseng (import), oat, and rye.

2.1 Data Deficiencies

The following data are required: 

870.7800 Immunotoxicity Study

In 2007, the Agency revised 40 CFR Part 158.500 Toxicology data requirements to 

include functional immunotoxicity testing and granted a 2-year grace period to allow time 

for registrants to develop the required data. Syngenta estimated that the immunotoxicity 

study would be completed in November 2011. The immunotoxicity study is required for 

azoxystrobin under Registration Review and is due in 2012. A waiver request has been 

submitted and is pending review. 

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method 

Adequate residue analytical methods are available for tolerance enforcement: a gas 

chromatography method with nitrogen-phosphorus detection (GC/NPD), RAM 243/04, for the 

analysis of crop commodities with azoxystrobin and its Z-isomer; and a GC-NPD method, RAM 

255/01, for analysis of livestock commodities for residues of azoxystrobin. 

2.2.2 International Harmonization

Codex Maximum Residue Limits (MRLs) have been proposed for azoxystrobin in ginseng at 0.1 

ppm and dried ginseng including red ginseng at 0.5 ppm. A proposed MRL ginseng, processed 

products at 0.5 ppm has been returned to JMPR for further consideration of the processing study. 

A Canadian MRL has been established for residues of azoxystrobin including the (Z)-isomer in 

ginseng roots at 0.5 ppm and at 0.03 ppm for barley, oats, rye, and wheat. Mexico adopts US

tolerances and/or Codex MRLs for its export purposes. Residue definitions are not harmonized 

with Codex; the US residue definition includes both the predominant E isomer and the minor Z

isomer whereas the Codex includes only the E isomer. The Codex MRLs on barley grain and

wheat grain are estimated at 0.5 and 0.2 ppm, respectively, and MRLs for oats and rye are 

extrapolated from the data on barley and wheat, respectively. The US and Codex MRLs are not 

in harmony for all proposed crops. The US tolerances on oat grain (1.5 ppm) and barley grain (3 

ppm) could not be harmonized since the Codex MRLs are lower. HED recommends increasing 

the US tolerances of ginseng to 0.5 ppm and to 0.2 ppm for rye and wheat grain to harmonize the 

numerical portion of the tolerance with the Codex MRL. The Canadian MRL was harmonized 

only in ginseng roots. 

2.2.3 Recommended Tolerances 
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Pending submission of a revised Section F, HED can recommend for establishment of permanent 

tolerances for azoxystrobin in/on ginseng and cereal grains. The tolerance values proposed by 

the petitioner need to be revised for all commodities as listed in the table below. The 

Organization for Economic Cooperation and Development (OECD) tolerance calculation 

procedures (March 2011 version) were utilized in determining the appropriate tolerance level. 

Table 2.2.3. Tolerance Summary for Azoxystrobin

Commodity Proposed Tolerance

(ppm)

Recommended 

Tolerance (ppm)

Comments; Correct Commodity 

Definition

Ginseng Extract (Red 

Ginseng Extract and 

Ginseng Extract)

0.5 -- The US does not currently regulate 

any processed commodity of ginseng; 

therefore, this tolerance is not 

needed.

Ginseng -- 0.5 Based on data for dried ginseng root, 

to harmonize with Codex.

Oat, forage 4 5

Oat, hay 7 10

Oat, straw 3 3

Oat, grain 1 1.5

Rye, forage 4 7

Rye, straw 0.8 1.5

Rye, grain 0.07 0.2 To harmonize with Codex.

Barley, hay 7 10

Barley, straw 8 15

Barley, grain 2 3

Wheat, forage 10 15

Wheat, straw 6 10

Wheat, hay 20 30

Wheat, grain Not proposed 

(Established at 0.10)

0.2 Based on data/to harmonize with 

Codex.

Grain, aspirated fractions 460

(Established at 420)

420 The established tolerance of 420 ppm 

is sufficient.

Grain, aspirated grain fractions 

Livestock Commodities Requested To be Revised

Cattle, fat 0.3 Not Needed
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Hog, fat 0.1

Hog, meat 0.02

Livestock Commodities Requested to be Established

Poultry, meat 0.01

Poultry, liver 0.2

Poultry, fat 0.01

Egg 0.1

Cattle, liver 0.5

Cattle, kidney 0.1

Hog, liver 0.2

Hog, kidney 0.03

Note to PM: In conjunction with establishment of wheat grain tolerance at 0.2 ppm, the 

existing tolerance on wheat bran need to be removed from 40 CFR §180.507(a)(1). 

Note to PM: The tolerance expression in 40 CFR §180.507(a)(2) is incorrect. Therefore, the 40 

CFR §180.507(a)(2) should be revised to specify the following tolerance expression: Tolerances 

are established for residues of the fungicide, azoxystrobin, including its metabolites and 

degradates, in or on the commodities in the following table. Compliance with the tolerance 

levels specified in the table is to be determined by measuring only azoxystrobin, [methyl(E)-2-

(2-(6-(2-cyanophenoxy) pyrimidin-4-yloxy)phenyl)-3-methoxyacrylate] in or on the commodity.

2.2.4 Revisions to Petitioned-For Tolerances

Based on the available data, the proposed tolerances for all commodities must be revised to 

reflect the appropriate tolerance levels estimated using adjusted residue values to reflect the 

higher application rate of the Abound® label. The proposed tolerances are based on residue data 

submitted using lower application rates which do not cover the highest proposed rate. A revised 

Section F needs to be submitted to reflect the recommended tolerances as listed in Table 2.2.3. 

2.3 Label Recommendations

None 

3.0 Introduction

Azoxystrobin is a broad spectrum fungicide used to control many plant diseases, such as early 

and late leaf spot in peanuts, late blight in pistachios, brown rot blossom blight, and fruit rot in 

stone fruits; and leaf and fruit spot in tree nuts. It has the same biochemical mode of action as 

the naturally occurring strobilurins and is structurally related. Azoxystrobin is a -

methoxyacrylate, and acts by inhibiting electron transport. 

Syngenta has requested azoxystrobin be registered for use on ginseng (import), oats, and rye. 

Concurrently, Syngenta is requesting revision of the established tolerances on wheat and barley 

commodities due to amendments of PHIs. Azoxystrobin is currently registered for use on a 

variety of vegetable, fruit, cereal, and nut crops, as well as on ornamental plants and turf. 
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Tolerances are currently established for barley bran (6.0 ppm), forage (25 ppm), grain (3.0 ppm), 

hay (15 ppm), and straw (7 ppm); wheat bran (0.20 ppm), forage (25 ppm), grain (0.10 ppm), 

hay (15 ppm), and straw (4 ppm). The proposed uses of azoxystrobin are expected to result in 

occupational exposure only; no residential exposure is expected from the proposed uses of 

azoxystrobin. Only short- and intermediate-term occupational exposures were assessed for the 

proposed uses of azoxystrobin. The formulated end use products (EPs) evaluated in this 

assessment are Abound® Flowable Fungicide (22.9% ai) (EPA Reg. No. 100-1098), Quilt 

Xcel® (13.5% ai) (EPA Reg. No. 100-1324), and Quilt® Fungicide (0.62 lb ai) (EPA Reg. No. 

100-1178). Quilt Xcel® and Quilt® are multiple active ingredient (MAI) product formulations 

containing both azoxystrobin and propiconazole (11.7% for both). In addition, Syngenta is 

requesting to add oats and rye use on three azoxystrobin manufacturing products: Azoxystrobin 

Manufacturing Use Concentrate (MUC) (EPA Reg. No. 100-1119), Azoxystrobin Dry Technical 

Manufacturing Use Concentrate (MUC) (EPA Reg. No. 100-1120), and Azoxystrobin Millbase 

Manufacturing Use Product (MUP) (EPA Reg. No. 100-1220).

Azoxystrobin (20% SC formulation; Ortiva) is proposed for use on ginseng as four foliar 

applications at 10 mL formulated product/20 mL water with a 7-day pre-harvest interval (PHI). 

Based on the additional use pattern information submitted, the single application rate is 379.75 g 

ai/ha (0.34 lb ai/A) with maximum application rate of 1519 g ai/ha (1.36 lb ai/A). 

Azoxystrobin is proposed for use as a foliar application on oats and rye using ground, aerial, and 

chemigation equipment. The use profile is summarized in Table 3.3. The proposed single 

application rates on cereals (wheat, triticale, barley, oats, and rye) range from 0.07-0.20 lb ai/A 

(4-12.0 fl oz product/A) for Abound® Flowable Concentrate and 0.03-0.13 lb ai/A (7-14 fl oz 

product/A) for Quilt Xcel® and Quilt. The Abound®, Quilt Xcel®, and Quilt® labels specifiy 

that no more than 0.40 lb ai/A of any azoxystrobin containing products should be applied per 

season, and no more than 2 foliar applications should be applied per season. All labels require a 

7-day PHI for forage and hay. There is a growth stage restriction for the last application to not 

apply later than Feekes Growth Stage 10.54 (BBCH 71).

3.1 Chemical Identity

The chemical structure and nomenclature of azoxystrobin are presented in Table 3.1.

Table 3.1. Azoxystrobin Nomenclature.

Compound

Common name Azoxystrobin

Company experimental name ICIA5504 (Zeneca), R215504 (Syngenta)

IUPAC name methyl (2E)-2-{2-[6-(2-cyanophenoxy)pyrimidin-4-yloxy]phenyl}-3-

methoxyacrylate

N N

O O

CN OCH3

O

H3CO
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Table 3.1. Azoxystrobin Nomenclature.

CAS name methyl (αE)-2-[[6-(2-cyanophenoxy)-4-pyrimidinyl]oxy]-α-(methoxymethylene)-

benzeneacetate

CAS registry number 131860-33-8

End-use products (EP) 20% SC formulation (Azoxystrobin SC; Ortiva); Abound® Flowable Fungicide 

(EPA Reg. No. 100-1098); Quilt® Fungicide (EPA Reg. No. 100-1178); and 

Quilt Xcel® Fungicide (EPA Reg. No. 100-1324).

Regulated metabolite, Zisomer

Common name Azoxystrobin, Z-isomer

Chemical name methyl (Z)-2-{2-[6-(2-cyanophenoxy)pyrimidin-4-yloxy]phenyl}-3-

methoxyacrylate

3.2 Physical/Chemical Characteristics

Azoxystrobin has a log octanol/water partition coefficient (log P) of 2.5 and is considered 

relatively insoluble in water. However, azoxystrobin has a molecular weight of 403 g/mol; 

therefore, the potential to cross biological barriers is somewhat limited, as indicated by the low 

dermal absorption in the rat dermal penetration study. In the cattle feeding study, azoxystrobin 

concentrated in cream. No quantifiable azoxystrobin residues were found in cattle muscle even 

at the highest dosing level, whereas quantifiable residues were observed in fat. The 

physicochemical properties of azoxystrobin are summarized in Appendix B. 

3.3 Pesticide Use Pattern

Syngenta has submitted a draft label with English translations for the 20% SC formulation of 

azoxystrobin (Azoxystrobin SC; Ortiva) reflecting established use patterns in Korea in support of 

the requested import tolerance on ginseng. Syngenta has also submitted draft supplemental 

amended labels adding uses on oats and rye for Abound® Flowable Fungicide (EPA Reg. No. 

100-1098), Quilt Xcel® (EPA Reg. No. 100-1324), and Quilt® Fungicide (EPA Reg. No. 100-

1178). In addition, Syngenta is requesting to add oats and rye use on three azoxystrobin 

manufacturing products: Azoxystrobin Manufacturing Use Concentrate (MUC) (EPA Reg. No. 

100-1119), Azoxystrobin Dry Technical Manufacturing Use Concentrate (MUC) (EPA Reg. No. 

100-1120), and Azoxystrobin Millbase Manufacturing Use Product (MUP) (EPA Reg. No. 100-

1220). Table 3.3 provides a summary of the proposed use sites of azoxystrobin. 

N N

O O

CN

O OCH3

H3CO
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Table 3.3.1 Summary of Directions for Use of Azoxystrobin on Ginseng.

Applic. Timing;

Type; and Equip.

FormulationApplic. 

Rate1

Max. No. 

Applic. per 

Season

Max. Seasonal 

Applic. Rate

PHI

(days)

Use Directions and 

Limitations

Ginseng

Foliar; 

Broadcast; 

Equipment not 

specified

20% SC 10 mL 

formulated 

product/

20 L water

4 Not specified:

Run-off 

spraying is 

recommended

7 Applications are to be made 

at the beginning of 

infestation after leaves are 

fully opened with a 10-day 

retreatment interval (RTI). 

Use of surfactants or 

penetration stimulators is 

prohibited.

Table 3.3.2 Summary of Directions for Use of Azoxystrobin on Cereals.

Applic. Timing, 

Type, and Equip. 

Formulation

[EPA Reg. 

No.]

Applic. Rate

fl oz/A

(lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. 

Rate

fl oz/A

(lb ai/A)

PHI

(days) Use Directions and Limitations2

Cereals (Wheat, Triticale)

Foliar

Ground, aerial or 

chemigation

2.08 lb 

ai/gal SC

[100-1098]

4.0-12

(0.07-0.20) 2

1

0.40

7-forage 

and hay

Applications are to be made prior 

to disease development.

A crop oil concentrate adjuvant 

may be added at 1.0% v/v to 

optimize efficacy.

Foliar

Ground, aerial or 

chemigation

SE/MAI 

(0.62 lb 

ai/gal)

[100-1178]

7-14

(0.03-0.07) 2

1 28

(0.14)

7-forage 

and hay

Apply Quilt in the spring for 

suppression of early season 

diseases. Follow up with a 

second application for full season 

control. For high yields apply 

Quilt when flag leaf is 50% to 

full head emergence (Feekes 

10.5).

Applications may be made no 

closer than a 14-day interval. 

Foliar

Ground, aerial or 

chemigation

SE/MAI 

(1.18 lb 

ai/gal)

[100-1324]

7-14

(0.06-0.13) 2

1 28

(0.26)

7-forage 

and hay

Cereals (Barley, Oat and Rye) 100-1178, 100-1324 includes Triticale

Foliar

Ground, aerial or 

chemigation

2.08 lb 

ai/gal SC

[100-1098]

6-12

(0.10-0.20)

2

1

0.40

7-forage

and hay

Applications are to be made prior 

to disease development.

Minimum volume for aerial 

applications is 5 gal/A. 

Foliar

Ground, aerial or 

chemigation

SE/MAI 

(0.62 lb 

ai/gal)

[100-1178]

7-14

(0.03-0.07) 2

1 28

(0.14)

7-forage 

and

hay

Apply Quilt in the spring for 

suppression of early season 

diseases. Follow up with a 

second application for full season 

control. For high yields apply 
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Table 3.3.2 Summary of Directions for Use of Azoxystrobin on Cereals.

Applic. Timing, 

Type, and Equip. 

Formulation

[EPA Reg. 

No.]

Applic. Rate

fl oz/A

(lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. 

Rate

fl oz/A

(lb ai/A)

PHI

(days) Use Directions and Limitations2

Foliar

Ground, aerial or 

chemigation

SE/MAI 

(1.18 lb 

ai/gal)

[100-1324]

7-14

(0.06-0.13) 2

1 28

(0.26)

7-forage 

and hay

Quilt when flag leaf is 50% to 

full head emergence (Feekes 

10.5).

Applications may be made no 

closer than a 14-day interval.

An adjuvant may be added at 

recommended rates. 

1 For resistance management, no more than two sequential applications of Abound Flowable Fungicide or other

Group 11 fungicides should be made before alternating with a fungicide having a different mode of action (not in 

Group 11). Do not make more than two foliar applications of Abound Flowable Fungicide or other Group 11 

fungicide per season.

2 Applications may be made no closer than a 14-day interval (For Quilt and Quilt Xcel).

Do not apply after Feekes 10.54.

Do not apply more than 0.40 lb ai/A per season of azoxystrobin-containing products.

3.4 Anticipated Exposure Pathways

The Registration Division has requested an assessment of human health risk to support the 

proposed new use of azoxystrobin on ginseng, oat, and rye. Humans may be exposed to 

azoxystrobin in drinking water, since application may result in azoxystrobin reaching surface and 

ground water sources of drinking water. Humans may also be exposed through their diet from 

applications to agricultural commodities. There are residential uses of azoxystrobin, so exposure 

to azoxystrobin may occur in residential or non-occupational settings. In an occupational setting, 

handlers may be exposed while handling the pesticide prior to application, as well as during 

application. There is also a potential for post-application exposure for workers re-entering 

treated sites. 

Risk assessments have been completed for the existing uses of azoxystrobin. This risk 

assessment considers all of the aforementioned exposure pathways based on the proposed new 

uses of azoxystrobin, but also considers existing uses of azoxystrobin, particularly in the dietary 

exposure assessment. 

3.5 Consideration of Environmental Justice

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. 
Azoxystrobin Human Health Risk Assessment DP No. 402285

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Extensive data on food consumption patterns are compiled by the U.S. Department of 

Agriculture’s National Health and Nutrition Examination Survey, What We Eat in America

(NHANES/WWEIA) 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 toddlers, youths 

and adults entering or playing on treated areas post-application are evaluated. Further 

considerations are currently in development as OPP has committed resources and expertise to the 

development of specialized software and models that consider exposure to bystanders and farm 

workers as well as lifestyle and traditional dietary patterns among specific subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

- Azoxystrobin: Human Health Risk Assessment for Proposed Uses on Dragon Fruit, Wasabi, and Tuberous and 

Corm Vegetables (Subgroup 1C), and from the Revisions to Various Crop Groups (Onion Subgroups 3-07 A, B; 

Fruiting Vegetable Subgroups 8-10 A,B; Small Fruit and Berry Subgroups 13-07 A, B, F, G, Oilseeds 

Subgroups A, B, C; and Citrus Fruit Group 10-10). K. Rury, DP# 389702, 01/18/2012. 

A detailed hazard characterization with a list of available toxicity studies for azoxystrobin is 

presented in the previous risk assessment (K. Rury, D389702, 01/18/2012). The submitted 

studies are of good quality and provide sufficient information to determine whether azoxystrobin 

poses a human health hazard. In addition, the registrant, Syngenta, has committed to submitting 

an adequate functional immunotoxicity study that is currently underway and expected to be 

submitted to the Agency in 2012. A waiver request has been submitted and is pending review. 

4.1 Toxicological Effects

Azoxystrobin has a low acute toxicity via the oral, dermal and inhalation routes of exposure. It 

produced light irritation to eye and skin, but the effects were cleared by 48 hours for the eye and 

three days for the skin. Dietary administration of azoxystrobin to rats resulted in decreased body 

weights, decreased food intake and utilization, increased diarrhea, and other clinical toxicity 

observations (increased urinary incontinence, hunched postures, and distended abdomens). In 

addition, liver effects, characterized by increased liver weights, increases in alkaline phosphatase 

and gamma glutamyltransferase, decreases in albumin, and gross and histological lesions in the 

liver and bile ducts, were seen in rats. In dogs, effects on liver/biliary function were found after 

oral administration. 

In the acute neurotoxicity study in rats, increased incidence of diarrhea was observed at all dose 

levels tested including the LOAEL. Decreased body weight, decreased body weight gain, and 

food utilization was noted in the rat subchronic neurotoxicity study. There were no indications 

of treatment-related neurotoxicity in either the acute or subchronic neurotoxicity studies. 

In the rat developmental toxicity study, diarrhea, urinary incontinence, and salivation were 

observed in maternal animals; in the rabbit developmental toxicity study, maternal animals 

exhibited decreased body weight gain. No adverse treatment-related developmental effects were 
Azoxystrobin Human Health Risk Assessment DP No. 402285

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seen in either study. In the rat reproduction study, offspring and parental effects (decreased body 

weights and increased adjusted liver weights) were observed at the same dose.

There was no evidence of carcinogenicity in rats and mice. As a result, EPA has classified 

azoxystrobin as “not likely to be carcinogenic to humans.” Azoxystrobin induced a weak 

mutagenic response in the mouse lymphoma assay, but the activity expressed in vitro is not 

expected to be expressed in whole animals.

4.2 Safety Factor for Infants and Children (FQPA Safety Factor)

EPA has retained the FQPA SF, reduced to 3X, in assessing acute dietary risk. An additional 

safety factor is needed for acute risk assessment to account for the use of a LOAEL from the 

acute neurotoxicity study in rats in deriving the acute reference dose used for assessing acute 

dietary exposure for all populations including infants and children. To account for the use of a 

LOAEL from the acute neurotoxicity study in rats, the Agency believes that a 3X FQPA SF (as 

opposed to a 10X) will be adequate to extrapolate a NOAEL in assessing acute risk and that no 

additional safety factor is needed for short-term, intermediate-term, and chronic risk assessment 

based on the following considerations:

a. the effect seen (transient diarrhea seen in the rat) is of a nature that is relatively 

insignificant;

b. the diarrhea was only seen in studies involving gavage dosing in the rat but not in 

repeat dosing through dietary administration in rats and mice, and not through 

gavage dosing in rabbits; and 

c. the very high dose level needed to reach the acute oral lethal dose (LD)50 (>5000 

milligrams/kilogram (mg/kg)), and the overall low toxicity of azoxystrobin. 

However, EPA has determined that reliable data show that it would be safe for infants and 

children to reduce the FQPA safety factor to 1X for short-term, intermediate-term, and chronic 

risk assessment. This determination is based on the following considerations: 

4.2.1 Completeness of the Toxicology Database

The toxicity database for azoxystrobin is complete except for immunotoxicity and subchronic 

inhalation toxicity testing. Changes to 40 CFR part 158 make immunotoxicity testing (OPPTS 

Guideline 870.7800) required for pesticide registration; however, the existing data are sufficient 

for endpoint selection for exposure/risk assessment scenarios, and for evaluation of the 

requirements under the FQPA. There are no indications in the available studies that organs 

associated with immune function, such as the thymus and spleen, are affected by azoxystrobin 

and azoxystrobin does not belong to a class of chemicals that would be expected to be 

immunotoxic. Based on the above considerations, EPA does not believe that conducting the 

immunotoxicity study will result in a dose less than the point of departure already used in this 

risk assessment, and an additional database uncertainty factor for potential immunotoxicity does 

not need to be applied. 

A subchronic inhalation toxicity study has been waived by HASPOC (TXR# 0056307). 

4.2.2 Evidence of Neurotoxicity
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Clinical signs, including transient diarrhea and decreased body weight, body weight gain, and 

food utilization, were noted in the acute and subchronic neurotoxicity studies, but were not 

considered indicative of neurotoxicity. There is no need for a developmental neurotoxicity study 

or additional UFs to account for neurotoxicity.

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

There is no evidence that azoxystrobin results in increased susceptibility to in utero rats or 

rabbits in the prenatal developmental studies or in young rats in the 2-generation reproduction 

study. 

4.2.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the azoxystrobin exposure database. While some 

refinements were incorporated into the dietary exposure calculations, EPA is confident that the 

aggregate risk from exposure to azoxystrobin in food, drinking water, and residential pathways 

will not be underestimated. The acute dietary (food) exposure assessment utilized conservative 

upper-bound inputs including 100% of the proposed and registered crops treated, and tolerancelevel residues for all existing and proposed commodities, except citrus fruits where the highest 

field trial residue was used as a refinement. The chronic dietary exposure assessment was 

partially refined, and used tolerance-level residues for all commodities and % CT estimates when 

available (Screening Level Usage Analysis (SLUA), 07/13/11). Although the acute and chronic 

assessments included minor refinements, the use of field trial and % CT estimates ensures that 

actual exposures/risks from residues in food will not be underestimated. The drinking water 

assessment utilized water concentration values generated by models and associated modeling 

parameters which are designed to produce conservative, health protective, high-end estimates of 

water concentrations which are not likely to be exceeded. The dietary (food and drinking water) 

exposure assessment does not underestimate the potential exposure for infants, children, or 

women of child bearing age. 

In addition, the residential exposure assessment is based on the updated 2012 Residential SOPs 

employing surrogate study data, including conservative exposure assumptions based on Day 0 

dermal/oral contact to turf and surfaces treated at the maximum application rate. These data are 

reliable and are not expected to underestimate risks to adults or children. The Residential SOPs 

are based upon reasonable “worst-case” assumptions are not expected to underestimate risk. 

4.3 Toxicity Endpoint and Point of Departure Selections

4.3.1 Summary of Points of Departure and Toxicity Endpoints Used in Human Health 

Risk Assessment 

The toxicological doses and endpoints supporting this petition remain unchanged and have been 

summarized in the previous human health risk assessment (K. Rury, D389702, 01/18/2012). The 

toxicity endpoints and PODs are presented in Table 4.3.1.
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Table 4.3.1. Summary of Toxicological Doses and Endpoints for Azoxystrobin for Use in Dietary, NonOccupational and Occupational Human Health Risk Assessments.

1

Exposure/

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, Level of 

Concern for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary

(All 

Populations)

LOAEL = 200 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 

3X

Acute RfD = 

0.67mg/kg/day

aPAD = 0.67

mg/kg/day

Acute Neurotoxicity - Rat. LOAEL 

= 200 mg/kg/day based on diarrhea at 

two-hours post dose at all dose levels 

including the LOAEL.

Chronic 

Dietary (All 

Populations)

NOAEL = 18

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 

1X

Chronic RfD = 0.18 

mg/kg/day

cPAD = 0.18

mg/kg/day

Combined Chronic 

Toxicity/Carcinogenicity Feeding 

Study – Rat. LOAEL = 82.4/117 

mg/kg/day (M/F) based on reduced 

body weights in both sexes and bile 

duct lesions in males.

Incidental 

Oral ShortTerm (1-30 

days)

NOAEL = 25

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 

1X

Residential LOC for 

MOE = 100

Prenatal Developmental Oral 

Toxicity – Rat. LOAEL = 100 

mg/kg/day based on increased 

maternal diarrhea, urinary 

incontinence, and salivation.

Incidental 

Oral 

IntermediateTerm (1-6 

months)

NOAEL = 20

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 

1X

Residential LOC for 

MOE = 100

90-day Feeding Study – Rat. 

LOAEL = 211/223 mg/kg/day (M/F) 

based on decreased body weight gain 

in both sexes and clinical signs 

indicative of reduced nutrition.

Dermal 

(All 

Durations)

No hazard was identified for this exposure scenario. 21-Day Repeated Dose Dermal Study 

– Rat. No dermal or systemic 

toxicity was seen at the limit dose 

(1,000 mg/kg/day).

Inhalation 

Short-Term 

(1-30 days)

Oral NOAEL 

= 25

UFA = 10X

UFH = 10X

FQPA SF = 

1X

Occupational & 

Residential LOC for 

MOE = 100

Prenatal Developmental Oral 

Toxicity – Rat. LOAEL = 100 

mg/kg/day based on increased 

maternal diarrhea, urinary 

incontinence, and salivation.

Inhalation 

IntermediateTerm

(1-6 months)

Oral NOAEL 

= 20

UFA = 10X

UFH = 10X

FQPA SF=1X

Occupational & 

Residential LOC for 

MOE = 100

90-day Feeding Study – Rat. 

LOAEL = 211/223 mg/kg/day (M/F) 

based on decreased body weight gain 

in both sexes and clinical signs 

indicative of reduced nutrition.

Cancer 

(oral, dermal, 

inhalation)

Azoxystrobin is classified as "Not Likely" to be carcinogenic to humans.

1. 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. N/A = not applicable.

2. Dermal penetration study showed low absorption factor (2-4%).

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

risk for azoxystrobin 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 
Azoxystrobin Human Health Risk Assessment DP No. 402285

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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 azoxystrobin and/or re-examine the inhalation 

toxicity risk assessment.

5.0 Dietary Exposure and Risk Assessment 

5.1 Metabolite/Degradate Residue Profile

5.1.1. Summary of Metabolism Studies, Environmental Degradation, and Metabolic 

Pathway Comparison

The nature of the residue in plants and livestock are adequately understood for the purposes of 

the Syngenta petition. Metabolism studies in grapes, peanuts, and wheat were submitted in 

conjunction with earlier azoxystrobin petitions, PP#s 5F4541 and 6F4762. No new plant or 

metabolism studies have been submitted for azoxystrobin since the last human health risk 

assessment; therefore, the metabolic profile remains unchanged (K. Rury, D389702, 

01/18/2012). A more detailed description of the plant and animal metabolism studies is 

presented in the previous risk assessment (K. Rury, D389702, 01/18/2012). The database is 

adequate for determining azoxystrobin residues of concern. The summary of environmental 

degradation of azoxystrobin also remains unchanged and has been summarized in the previous 

human health risk assessment (K. Rury, D389702, 01/18/2012). A summary of the metabolites 

and degradates of azoxystrobin for human health risk assessment is summarized in Table 5.1.2. 

5.1.2 Residues of Concern Summary 

Table 5.1.2. Summary of Metabolites and Degradates included in the Azoxystrobin Risk Assessment and 

Tolerance Expression.

Matrix Residues included in

Risk Assessment

Residues included in

Tolerance Expression

Plants Primary Crop Azoxystrobin and Z-isomer Azoxystrobin and Z-isomer

Rotational Crop Azoxystrobin and Z-isomer Azoxystrobin and Z-isomer

Livestock Ruminant Azoxystrobin Azoxystrobin

Poultry Azoxystrobin Azoxystrobin

Drinking Water Azoxystrobin Not Applicable

5.2 Food Residue Profile

Adequate residue data are available to support dietary risk assessment as well as the proposed 

tolerances of azoxystrobin on ginseng, oat, and rye.
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Residues are quantifiable in all crops. Residues tend to be surface residues and generally decline 

with increasing pre-harvest intervals (PHI). Processing studies indicate that residues concentrate 

in dried citrus pulp, citrus oil, dried basil, field corn oil, peanut oil, tomato paste, wheat bran, and 

wheat germ. Livestock feeding studies indicate low transfer of residues to meat and milk with 

the highest transfer in liver. No quantifiable residues were found in any poultry commodity.

Proposed Uses 

Crop field trials were submitted to support the tolerances on ginseng (import), oat, and rye. In 

addition, crop field trials on barley and wheat were submitted to support the PHI revisions 

requested on the registered labels for cereals (wheat, barley, and triticale) and remove the 45-day 

PHI for grain and straw and replace it with growth stage restriction for the last application on the 

proposed end use products. The established tolerances on barley and wheat commodities were 

revised due to these changes. 

The submitted crop field trial data for ginseng conducted in Korea are acceptable pending 

submission of a revised Section F.

The submitted crop field trial data for oat, rye, barley, and wheat are acceptable pending 

submission of Section F. Although the number of field trials is technically inadequate (oats and 

rye), HED concludes that the available data are sufficient to support registration of azoxystrobin 

on oats and rye because the field trials conducted cover all zones requested. The submitted 

wheat and barley data to change the PHIs of forage and hay from 14-30 days to 7-days, and 

replace the 45-day PHI with a growth stage restriction for grain and straw is acceptable.

The crop field trial data for oats, rye, barley, and wheat reflect the proposed use patterns of Quilt

® Fungicide (EPA Reg. No. 100-1178) and Quilt Xcel® Fungicide (EPA Reg. No. 100-1324). 

The submitted crop field trials were conducted using Quilt Xcel® with two foliar applications at 

0.13 lb ai/A/application for a total seasonal application rate of 0.26 lb ai/A. The crop field trial 

data do not reflect the proposed use pattern of the Abound® Flowable Fungicide (EPA Reg. No.

100-1098). The Abound® can be applied in a miximum of two foliar applications at 0.20 lb 

ai/A/application for a total seasonal application rate of 0.40 lb ai/A. The existing wheat 

tolerances were established using the Abound® according to the label rate. The current 

tolerances on barley were established based on translation of residue data from wheat. The 

submitted crop field trials were conducted at lower application rates than the Abound® label. 

Therefore, residue levels were adjusted using the proportionality rule before deriving a tolerance 

level to reflect the proposed highest application rate.

Syngenta submitted an acceptable processing study for azoxystrobin on wheat. Quantifiable 

total residues (azoxystrobin and Z-isomer) concentrate in aspirated grain fractions (218x), bran 

(1.4x), and germ (1.2x), but not in flour, middlings, and shorts (0.3x, 0.4x, 0.5x, respectively)

following processing of the RAC (wheat grain). All of the processing factors calculated in this 

study were less than the maximum theoretical concentration factors for wheat (7.7x for bran, 

1.4x for flour, and 8.3x for shorts).

Acceptable methods were used for the determination of residues of azoxystrobin and the Zisomer metabolite. The sample storage conditions and durations are supported by adequate 
Azoxystrobin Human Health Risk Assessment DP No. 402285

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storage stability data which demonstrate that azoxystrobin and its Z-isomer are stable for at least 

24 months in water- starch-, protein-, oil-, and acid containing materials under frozen conditions. 

A summary of the residue data from the field trials including the wheat processing study are 

provided in Tables 5.2.a.-5.2.f.

Table 5.2a. Summary of Residue Data from Ginseng Crop Field Trials with Azoxystrobin.

Commodity Plot1 Total App. 

Rate 

lb ai/A

(g ai/ha)

PHI Residue Levels (ppm)1

n Sample 

Min.

Sample 

Max.

LAFT2 HAFT2 Median Mean Std. 

Dev.

Ginseng (proposed use = 10 mL formulated product/20 L water, 7-day PHI)

MRID 48601203

Ginseng, 

dried root

2008 trials 1.98

(2,222)

7 2 0.10 0.14 0.12 0.13 0.13 0.13 N/A

MRIDs 48601201 and 48601202

Ginseng, 

dried root

1a

(2009 trials)

1.21-1.29 

(1,355-1,450)

7 2 0.034 0.049 0.034 0.048 0.041 0.041 N/A

1b

(2009-2010 

trials)

2.43-2.58

(2,724-2,894)

7 2 0.060 0.179 0.063 0.177 0.120 0.120 N/A

The 2008 trials and Plot 1a received four foliar applications in year 1; plot 1b received four additional foliar 

applications in year 2 according to the same use pattern. The total seasonal application rate for Plot 2b was 1.221-

1.288 lb ai/A (1,369-1,444 g ai/ha). 

Table 5.2b. Summary of Residue Data from Oat Crop Field Trials with Azoxystrobin.

CommodityAnalyte Total App. 

Rate 

(lb ai/A) 

PHI Residue Levels (ppm)1

n Sample 

Min.

Sample 

Max.

LAFT2 HAFT2 Median Mean Std. 

Dev.

Forage Azoxystrobin 0.2494-

0.2650

7 11 0.106 2.21 0.109 1.98 0.781 0.784 0.566

R230310 11 <0.01 0.124 <0.01 0.112 0.0312 0.0438 0.0345

Combined 11 <0.116 2.33 <0.119 2.09 0.815 0.826 0.597

Combined311 0.179 3.59 0.183 3.22 1.26 1.27 0.92

Azoxystrobin 14 11 0.0417 1.02 0.0513 0.970 0.262 0.391 0.314

R230310 11 <0.01 0.0734 <0.01 0.0679 0.0126 0.0297 0.0249

Combined 11 <0.0517 1.09 <0.0613 1.04 0.272 0.421 0.338

Hay Azoxystrobin 7 11 0.147 3.38 0.200 3.16 1.06 1.48 1.19

R230310 11 <0.01 0.220 <0.0120 0.198 0.0577 0.0930 0.0724

Combined 11 <0.157 3.59 <0.212 3.36 1.19 1.58 1.26

Combined311 0.242 5.53 0.326 5.17 1.83 2.43 1.94

Azoxystrobin 14 11 0.126 2.34 0.139 1.77 0.576 0.718 0.496

R230310 11 <0.01 0.181 <0.01 0.123 0.0435 0.0567 0.0402

Combined 11 <0.136 2.52 <0.149 1.89 0.619 0.774 0.534
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Table 5.2b. Summary of Residue Data from Oat Crop Field Trials with Azoxystrobin.

CommodityAnalyte Total App. 

Rate 

(lb ai/A) 

PHI Residue Levels (ppm)1

n Sample 

Min.

Sample 

Max.

LAFT2 HAFT2 Median Mean Std. 

Dev.

Grain Azoxystrobin 0.2532-

0.2696

25-48 11 0.0115 0.636 0.0127 0.374 0.0521 0.120 0.134

R230310 11 <0.01 0.121 <0.01 0.0709 0.0106 0.0238 0.0229

Combined 11 <0.0215 0.751 <0.0227 0.444 0.0626 0.144 0.157

Combined311 0.033 1.16 0.035 0.684 0.096 0.221 0.241

Straw Azoxystrobin 25-48 11 0.0429 0.934 0.0487 0.880 0.197 0.387 0.332

R230310 11 <0.01 0.146 <0.01 0.131 0.0189 0.0457 0.0438

Combined 11 <0.0529 1.08 <0.0587 1.01 0.215 0.432 0.373

Combined311 0.082 1.66 0.129 1.56 0.564 0.721 0.556

Table 5.2c. Summary of Residue Data from Rye Crop Field Trials with Azoxystrobin.

CommodityAnalyte Total App. 

Rate 

(lb ai/A) 

PHI Residue Levels (ppm)1

n Sample 

Min.

Sample 

Max.

LAFT2 HAFT2 Median Mean Std. 

Dev.

Forage Azoxystrobin 0.2571-

0.2617

6-8 4 1.03 1.54 1.05 1.52 1.25 1.27 0.227

R230310 4 0.0305 0.0955 0.0359 0.0955 0.0532 0.0595 0.0257

Combined 4 1.06 1.59 1.08 1.58 1.32 1.32 0.249

Combined34 1.63 2.45 1.66 2.43 2.02 2.04 0.384

Azoxystrobin 13-15 4 0.396 0.628 0.418 0.590 0.486 0.495 0.0794

R230310 4 0.0176 0.0301 0.0183 0.0299 0.0245 0.0243 0.0063

Combined 4 0.414 0.658 0.437 0.619 0.510 0.519 0.0853

Grain Azoxystrobin 0.2563-

0.2646

34-50 4 <0.01 0.0159 <0.01 0.0151 0.0100 0.0113 0.0026

R230310 4 <0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A

Combined 4 <0.02 <0.0259 <0.02 <0.0251 0.0200 0.0213 0.0026

Combined34 0.031 0.040 0.031 0.039 0.031 0.033 0.004

Straw Azoxystrobin 34-50 4 0.0911 0.495 0.0952 0.382 0.158 0.198 0.126

R230310 4 <0.01 0.0363 <0.01 0.0315 0.0198 0.0203 0.0091

Combined 4 <0.101 0.531 <0.105 0.414 0.178 0.219 0.135

Combined34 0.156 0.818 0.162 0.638 0.273 0.336 0.208

Table 5.2d. Summary of Residue Data from Barley Crop Field Trials with Azoxystrobin.

CommodityAnalyte Total App. 

Rate 

(lb ai/A) 

PHI Residue Levels (ppm)1

n Sample 

Min.

Sample 

Max.

LAFT2 HAF

T

2

Median Mean Std. 

Dev.

Hay Azoxystrobi

n

0.2532-

0.2674

7 9 0.448 3.77 0.451 3.62 0.834 1.49 1.20

R230310 9 0.0139 0.391 0.0181 0.343 0.0702 0.0976 0.100

Combined 9 0.462 4.16 0.469 3.96 0.904 1.59 1.28

Combined39 0.711 6.41 0.722 6.10 1.39 2.44 1.98

Azoxystrobi

n

14 9 0.145 2.93 0.150 2.73 0.337 0.856 0.878

R230310 9 <0.01 0.342 <0.0107 0.342 0.0343 0.0713 0.105
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Table 5.2d. Summary of Residue Data from Barley Crop Field Trials with Azoxystrobin.

CommodityAnalyte Total App. 

Rate 

(lb ai/A) 

PHI Residue Levels (ppm)1

n Sample 

Min.

Sample 

Max.

LAFT2 HAF

T

2

Median Mean Std. 

Dev.

Combined 9 0.156 3.27 0.160 3.07 0.371 0.926 0.973

Grain Azoxystrobi

n

0.2560-

0.2649

16-49 9 <0.01 1.07 <0.01 0.974 0.0366 0.183 0.314

R230310 9 <0.01 0.116 <0.01 0.112 0.0100 0.0273 0.0341

Combined 9 <0.02 1.19 <0.02 1.09 0.0466 0.210 0.350

Combined39 0.031 1.83 0.031 1.68 0.072 0.323 0.539

Straw Azoxystrobi

n

16-49 9 0.0835 3.83 0.0896 3.49 0.356 1.24 1.44

R230310 9 <0.01 0.463 <0.01 0.379 0.0295 0.131 0.157

Combined 9 0.0945 4.29 0.101 3.87 0.377 1.37 1.59

Combined39 0.146 6.61 0.156 5.96 0.581 2.11 2.45

Table 5.2e. Summary of Residue Data from Wheat Crop Field Trials with Azoxystrobin.

CommodityAnalyte Total App. 

Rate 

(lb ai/A) 

PHI Residue Levels (ppm)1

N Sample 

Min.

Sample 

Max.

LAFT2 HAFT2 Median Mean Std. 

Dev.

Forage Azoxystrobin 0.2534-

0.2668

7 15 0.0825 6.17 0.0898 5.91 0.799 1.67 1.85

R230310 15 <0.01 0.207 <0.01 0.175 0.0500 0.0597 0.0532

Combined 15 <0.0925 6.25 <0.0998 5.99 0.842 1.73 1.89

Combined315 0.142 9.62 0.154 9.225 1.30 2.66 2.91

Azoxystrobin 14-20 15 0.0289 1.65 0.0307 1.62 0.258 0.457 0.495

R230310 15 <0.01 0.0962 <0.01 0.0870 0.0161 0.0266 0.0235

Combined 15 <0.0389 1.75 <0.0407 1.71 0.274 0.483 0.518

Hay Azoxystrobin 7 15 0.171 15.6 0.194 14.7 1.28 2.79 3.82

R230310 15 <0.01 0.333 <0.01 0.271 0.0835 0.103 0.0911

Combined 15 <0.181 15.8 <0.204 14.8 1.36 2.89 3.87

Combined30.279 24.3 0.314 22.8 2.09 4.45 5.96

Azoxystrobin 14-20 15 0.0767 3.14 0.0816 2.73 0.534 0.858 0.888

R230310 15 <0.01 0.160 <0.01 0.138 0.0297 0.0519 0.0467

Combined 15 <0.0867 3.30 <0.0916 2.87 0.564 0.909 0.930

Grain Azoxystrobin 0.2475-

0.2669

24-64 15 <0.01 0.0795 <0.01 0.0764 0.0107 0.0176 0.0170

R230310 15 <0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A

Combined 15 <0.02 <0.0895 <0.02 <0.0864 0.0207 0.0276 0.0170

Combined315 0.031 0.138 0.031 0.133 0.032 0.042 0.026

Straw Azoxystrobin 24-64 15 0.0369 4.03 0.0377 4.00 0.546 0.991 1.14

R230310 15 <0.01 0.372 <0.01 0.358 0.0646 0.107 0.115

Combined 15 <0.0469 4.37 <0.0447 4.36 0.610 1.10 1.25

Combined315 0.072 6.73 0.069 6.71 0.939 1.69 1.92

1 Except for sample min/max, values reflect per trial averages; n = no. of field trials. For calculation of median, 

mean, and standard deviation, the LOQ (0.01 ppm) was used for any results reported as <LOQ. N/A = Not 

applicable.
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2 LAFT = lowest average field trial; HAFT = highest average field trial.

3 Adjusted combined residues.

Table 5.2f. Residue Data from Wheat Processing Study with Azoxystrobin.

RAC Processed 

Commodity

Total 

Rate

(lb 

ai/A)

PHI Residues (ppm)1[Average] Processing Factor2

Azoxystrobi

n

R230310 Combined Azoxystrobi

n

R230310 Combined 

Cheneyville, LA; 2009 (E17-9032)

Wheat Grain 

(RAC)

1.283 30 0.129, 0.119 

[0.124]

0.0136, 

0.0109 

[0.0123]

0.143, 

0.130 

[0.136]

-- -- --

AGF 28.1 2.82 30.9 227x 230x 227x

Bran 0.129 0.0163 0.145 1.0x 1.3x 1.1x

Flour 0.0273 <0.01 <0.0373 0.22x <0.82x <0.27x

Middlings 0.0535 <0.01 <0.0635 0.43x <0.82x <0.47x

Shorts 0.0814 <0.01 <0.0914 0.66x <0.82x <0.67x

Germ 0.114 0.0134 0.127 0.92x 1.1x 0.94x

Carrington, ND; 2009 (C13-9038)

Wheat Grain 

(RAC)

1.283 55 0.0524, 

0.0523, 

0.0529

[0.0525]

<0.01, 

<0.01, 

<0.01 

[<0.01]

<0.0624, 

<0.0623, 

<0.0629

[<0.0625]

-- -- --

AGF 12.1 0.942 13.0 230x >94x >209x

Bran 0.0887 0.0150 0.104 1.7x >1.5x >1.7x

Flour <0.01 ND <0.0200 <0.19x NC3<0.32x

Middlings 0.0115 <0.01 <0.0215 0.22x NC <0.34x

Shorts 0.0102 <0.01 <0.0202 0.19x NC <0.32x

Germ 0.0851 <0.01 <0.0951 1.6x NC <1.5x

Average4

Wheat Grain 

(RAC)

1.283 30-

55

-- -- --

AGF 228x >162x >218x

Bran 1.4x >1.4x >1.4x

Flour <0.21x <0.91x <0.30x

Middlings 0.33x <0.91x <0.40x

Shorts 0.43x <0.91x <0.50x

Germ 1.3x <1.1x <1.2x

1 The LOQ was 0.01 ppm for all analytes in all matrices. Per trial average residues were calculated by the study 

reviewer using the LOQ for all residues reported as <LOQ. ND = Not detected. Residues were not adjusted. 

2

Processing Factor = [Measured residue for analyte in the processed fraction] / [Measured residue for analyte in the 

grain RAC]. 

3 NC = Not calculated; residues were below the LOQ in both RAC and processed fraction.

4

In the calculation of the average processing factor, a value of 1.0 was used when a processing factor was not 

calculated due to residues <LOQ in the processed fraction.
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Livestock

The additional livestock feedstuffs associated with this petition are grain, forage, hay, and straw 

of oats, and rye. The established tolerances for hay and straw of wheat and hay of barley will 

increase based on the submitted data, but were not included in the current dietary burden 

estimate since these tolerances will not affect the total estimated dietary burden. HED has 

recently revised its approach to calculating dietary burdens, replacing tolerance values in the 

calculation with HAFT residues for most feedstuffs, median residues for blended feeds, and 

median residues x processing factors for most processed commodities. This has generally 

resulted in appreciably lower dietary burdens for all species. The proposed commodities are fed 

to beef and dairy cattle, but are not fed to poultry or swine, except oat and rye grain which are 

fed to poultry. The previously estimated dietary burden (D390152, M. Negussie, 01/04/2012), 

will not be affected since the recommended tolerances and the percents of the diets are much 

lower for oat and rye commodities.

The existing azoxystrobin tolerances for milk, milk fat, meat, and the meat byproducts of goat,

hog, horse, and sheep are adequate. Revisions to the existing tolerances are not needed to 

support the proposed uses of azoxystrobin. The proposed uses of azoxystrobin addressed in this 

document do not alter the Agency’s previous conclusion that there is no reasonable expectation 

of finite residues in poultry commodities [Category 3 of §180.6(a)]. Tolerances are not needed 

for poultry tissues or eggs. 

Rotational Crops

Limited field rotational crop studies, reflecting applications made to the primary crop at a 

seasonal rate of 0.8-2.0 lb ai/A, were previously reviewed. Because the proposed uses on oat and 

rye do not result in increased maximum seasonal application rates of azoxystrobin, no changes to 

the existing rotational crop restrictions are needed. Subsequent to the establishment of tolerances 

in/on oat and rye, the rotational crop restrictions on the registered labels for the Abound® and 

Quilt Xcel® Fungicides should be revised to change the PBIs for oats and rye to 0-days. HED 

assumes that the rotational crop restrictions specified on the Quilt labels are due to use of 

propioconazole.

 

5.3 Water Residue Profile

The drinking water inputs provided in the previous drinking water assessment on turf (J. Wolf, 

D371383, 01/6/2010) were more conservative than the most recent drinking water assessment on 

rye and oat (I. Abdel-Saheb, D400772, 07/25/2012). EFED estimates drinking water 

concentrations of a chemical based on the highest rate of application of the chemical on all 

registered and proposed crops. In the case of azoxystrobin, turf, a previously registered use, has 

the highest application rate (0.55 lb ai/A, 9 applications per year with a 10-day interval between 

applications). The assessment was completed with the Tier 1 screening model, FQPA Index 

Reservoir Screening Tool (FIRST). The model and its description is available at the EPA 

internet site: http://www.epa.gov/oppefed1/models/water/.
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The proposed rates of application for oat and rye are lower than for turf. Therefore, the EDWCs 

reported for turf are used. EDWCs recommended for use in the human health risk assessment 

for all proposed/registered crops are listed in Table 5.3. For ground water, the EDWC is 3.1 ppb. 

Table 5.3. Summary of Estimated Surface Water Concentrations for Azoxystrobin.

Scenario Surface Water Conc., ppb

Acute 173

Chronic (non-cancer) 33

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data & Percent Crop Treated Used in Dietary Assessment

The acute dietary exposure assessment of azoxystrobin is partially refined by using highest 

residue values for citrus fruits and assuming tolerance-level residues for all other existing and 

proposed commodities. 100% of the crops were assumed treated with azoxystrobin and DEEM 

version 7.81 default processing factors were used except where tolerances were established for 

processed commodities. 

The chronic dietary exposure assessment was partially refined, based on tolerance level residues 

for all existing and proposed commodities. A SLUA was provided by the Biological and 

Economic Analysis Division (BEAD) (07/13/2011). % CT estimates were used when available. 

HED utilized BEAD’s estimated % CT for the existing uses as follows: almonds, 25%; apricots, 

10%; artichokes, 25%; asparagus, 2.5%; green beans, 10%; blackberries, 5%; blueberries, 10%, 

broccoli, 5%; cabbage, 10%; cantaloupes, 10%; carrots, 10%; cauliflower, 2.5%; celery, 10%; 

cherries, 5%; corn, 2.5%; cotton, 5%; cucumbers, 20%; dry beans/peas, 1%; garlic, 60%; 

grapefruit, 20%; grapes, 5%; hazelnuts (filberts), 5%; lettuce, 2.5%; onions, 10%; oranges, 5%; 

peaches, 5%; peanuts, 15%; green peas, 2.5%; pecans, 2.5%; peppers, 15%; pistachios, 15%; 

potatoes, 35%; prunes, 2.5%; pumpkins, 20%; raspberries, 5%; rice, 35%; soybeans, 2.5%; 

spinach, 10%; squash, 15%; strawberries, 30%; sugar beets, 5%; sweet corn, 10%; tangerines, 

15%; tomatoes, 15%; walnuts, 1%; watermelon, 20%; and wheat, 2.5%.

5.4.2 Acute Dietary Risk Assessment

An acute dietary exposure assessment was conducted for the general U.S. population and all 

population subgroups (all infants, children 1-2, children 3-5, children 6-12, youth 13-19, adults

20-49, adults 50+ and females 13-49). The acute dietary exposure estimate for food and drinking 

water utilized 17% of the aPAD for the general U.S. population. The acute dietary exposure 

estimate for the highest reported exposed population subgroup, children 1-2 years old, utilized 

41% of the aPAD. The results are reported in Table 5.4.4. All population subgroups were below 

the LOC. 

The acute dietary exposure assessment is partially refined, i.e., based on the assumption of 

tolerance-level residues for all commodities, except citrus (which used the highest residues from 

residue trials [Grapefruit = 5.447 ppm, Orange = 4.014 ppm, Orange, peel = 5.538 ppm, Lemon 
Azoxystrobin Human Health Risk Assessment DP No. 402285

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and Lime = 9.202 ppm]), used empirical or default DEEM processing factors, and assumed 100 

% CT for all crops. 

5.4.3 Chronic Dietary Risk Assessment

A chronic dietary exposure assessment was conducted for the general U.S. population and all 

population subgroups. The chronic dietary exposure for food and drinking water utilized 7% of 

the cPAD for the general U.S. population. The chronic dietary exposure for the highest reported 

exposed population subgroup, children 1-2 years old, utilized 17% of the cPAD. The results are 

reported in table 5.4.4. All population subgroups were below the LOC. 

The chronic dietary exposure assessment is partially refined, i.e., based on the assumption of 

tolerance-level residues for all commodities, used empirical or default processing factors and % 

CT information for the crops listed in Section 5.4.1. 

5.4.4 Summary Table

Table 5.4.4. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Azoxystrobin.

Population Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary Cancer

Dietary 

Exposure 

(mg/kg/day)

% aPAD

Dietary 

Exposure

(mg/kg/day)

% cPAD

Dietary 

Exposure

(mg/kg/day)

Risk

General U.S. Population 0.114142 17 0.012290 6.8

Not Applicable

All Infants (< 1 year old) 0.140251 21 0.017162 9.5

Children 1-2 years old 0.276719 41 0.031142 17

Children 3-5 years old 0.230886 34 0.025217 14

Children 6-12 years old 0.133704 20 0.015693 8.7

Youth 13-19 years old 0.098862 15 0.009994 5.6

Adults 20-49 years old 0.099791 15 0.010809 6.0

Adults 50-99 0.091527 14 0.010301 5.7

Females 13-49 years old 0.101784 15 0.010307 5.7

1 Higher exposure values are bolded.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

This document addresses the proposed new agricultural uses of azoxystrobin on barley, oats, rye, 

wheat, and triticale; therefore, no new residential exposure is expected. However, there are 

currently registered uses of azoxystrobin by both commercial and residential handlers on 

residential use sites, including turf, ornamentals, indoor uses (carpet and hard surfaces), and in 

paints. Each of these existing residential use patterns has previously been assessed by HED and 
Azoxystrobin Human Health Risk Assessment DP No. 402285

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the resulting exposures and risk estimates do not exceed HED’s LOC. However, HED has 

recently updated the residential standard operating procedures (SOPs) and body weights to be 

used in all human health assessments. Therefore, all the existing residential use patterns have 

been reassessed for residential handler and post-application exposures using these new 

procedures and data (K. Rury, D394287, 03/30/2012). 

6.1 Residential Handler Exposure

The proposed uses of azoxystrobin do not involve applications by homeowners or commercial 

applicators to residential settings. However, azoxystrobin is currently registered for use by 

residential and commercial applicators on several residential/non-agricultural use sites; i.e., 

outdoor residential (lawns, ornamentals, flower gardens, vegetables, fruit and nut trees, berries 

and vines) and recreational (golf courses, parks and athletic fields) sites. Additionally, 

residential and commercial applicators may use azoxystrobin on indoor carpets/other surfaces, 

and in treated paints (preservative incorporation). All existing residential exposures have been 

reassessed to account for updates to HED’s 2012 Residential SOPs along with policy changes for 

body weight assumptions. It is assumed that most residential uses will result in short-term (1 to 

30 days) handler exposures. Residential handlers are assumed to be wearing short-sleeved shirts, 

short pants, shoes and socks during application of azoxystrobin. Because there was no dermal 

endpoint chosen for azoxystrobin, risk from exposure to azoxystrobin was assessed for the 

inhalation route only. Although PODs from an oral study were used to assess residential handler 

inhalation risks for azoxystrobin, HED does not believe this assessment is under-protective of 

adult handlers. 

HED’s LOC for the MOE is defined by the uncertainty factors that are applied to the assessment. 

HED applies a 10X factor to account for interspecies extrapolation and a 10X factor to account 

for intraspecies sensitivity. The total uncertainty factor that has been applied to the non-cancer 

risk assessment for azoxystrobin is 100X for residential exposure. Residential exposure and risk 

resulting in MOEs greater than or equal to 100 will not be of concern to HED. 

Table 6.1 lists the MOE of residential handler exposure and risk estimate using the updated 

residential SOPs (2012). The new exposure and risk estimates for all residential handler 

scenarios result in risk estimates that are greater than the LOC MOE of 100; therefore, they are 

not of concern to HED. The MOEs for adult handlers ranged from 2,400 (painting with an 

airless sprayer) to 1,000,000,000 (mixing/loading/applying [M/L/A] a wettable powder to 

gardens and trees using a hose-end sprayer). 

Table 6.1. Short-Term Residential Handler Non-Cancer Exposure and Risk Estimate for Azoxystrobin.

Exposure Scenario Level of 

Concern

Inhalation 

Unit 

Exposure 

(μg/lb ai)

Maximum 

Application 

Rate1

Area Treated or 

Amount 

Handled Daily2

Inhalation

Dose 

(mg/kg/day)3 MOE4

Applicator

Painting with Airless Sprayer 100 0.56 1.0% ai by 

weight

5 one-gallon 

cans

0.0149 2,400

Painting with a Brush 100 0.2 1.0% ai by 

weight

2 one-gallon 

cans

0.0005 50,000
Azoxystrobin Human Health Risk Assessment DP No. 402285

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Table 6.1. Short-Term Residential Handler Non-Cancer Exposure and Risk Estimate for Azoxystrobin.

Exposure Scenario Level of 

Concern

Inhalation 

Unit 

Exposure 

(μg/lb ai)

Maximum 

Application 

Rate1

Area Treated or 

Amount 

Handled Daily2

Inhalation

Dose 

(mg/kg/day)3 MOE4

Indoor Manually-Pressurized 

Handwand Wettable Powder 100 1.1 0.0047 (lb ai/gal) 0.5 gallons 0.000032 770,000

Indoor Manually-Pressurized 

Handwand Wettable Powder 

in WSB

100 1.1 0.0047 (lb 

ai/gal) 0.5 gallons 0.000032 770,000

M/L/A Wettable Powders to 

Turf [Hose End Sprayer] 100 0.022 0.95 (lb ai/A) 0.5 acres 0.00013 190,000

M/L/A Wettable Powder to 

Turf [Manually Pressurized 

Handwand or Backpack 

Sprayer]

100 1.1 0.011 (lb 

ai/gal) 5 gallons 0.00076 33,000

M/L/A Wettable Powders in 

WSB to Turf [Hose End 

Sprayer]

100 0.034 0.95 (lb ai/A) 0.5 acres 0.0002 120,000

M/L/A Wettable Powder in 

WSB to Turf [Manually 

Pressurized Handwand or 

Backpack Sprayer]

100 0.018 0.011 (lb 

ai/gal) 5 gallons 0.000012 2,000,000

M/L/A Wettable Powder 

Azoxystrobin to Gardens and 

Trees [Manually-Pressurized 

Handwand or Backpack 

Sprayer]

100 1.1 0.000125 (lb 

ai/gal) 5 gallons 0.0000086 2,900,000

M/L/A Wettable Powder 

Azoxystrobin to Gardens and 

Trees [Hose-End Sprayer]

100 0.0014 0.000125 (lb 

ai/gal) 11 gallons 0.000000024 1,000,000,000

M/L/A Wettable Powder 

Water Soluble Packets 

Azoxystrobin to Gardens and 

Trees [Manually-Pressurized 

Handwand or Backpack 

Sprayer]

100 0.018 0.000125 (lb 

ai/gal) 5 gallons 0.00000014 180,000,000

M/L/A Wettable Powder 

Water Soluble Packets 

Azoxystrobin to Gardens and 

Trees [Hose-End Sprayer]

100 0.034 0.000125 (lb 

ai/gal) 11 gallons 0.00000059 43,000,000

1 Based on registered or proposed label (Reg. No. 100-1229).

2 Exposure Science Advisory Council Policy #9.1.

3 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) x Conversion Factor (0.001 mg/μg) x Application Rate (lb ai/acre or gal) 

x Amount Handled (gallons/day) / BW (kg).

4 Inhalation MOE = Inhalation NOAEL (mg/kg/day) / Inhalation Dose (mg/kg/day). Short-term Inhalation NOAEL = 25 

mg/kg/day.

6.2 Post-Application Exposure

When determining the potential for residential exposure, the Agency considers residues, leaf to 

skin/hand residue transfer, children’s hand-to-mouth residue transfer, and exposure time. No 

dermal endpoint was chosen for azoxystrobin; therefore, a dermal post-application risk 
Azoxystrobin Human Health Risk Assessment DP No. 402285

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assessment was not conducted. Residential post-application inhalation exposure in outdoor 

settings is considered negligible; however, residential post-application inhalation exposure has 

been assessed. Post-application exposure in residential settings is expected to be short-term in 

duration only. Tables 6.2 lists the highest estimate based on updated assessments of residential 

post-application exposures and risk estimates. The MOEs ranged from 250 to 810,000 for 

incidental oral ingestion. The MOE for adults was 220,000,000, 000 and was 52,000,000,000 for 

children for indoor post-application inhalation exposure. The new exposure and risk estimates 

for all residential post-application uses result in risk estimates that are greater than the LOC 

MOE of 100, and therefore are not of concern to HED. 

A turf transferable residue (TTR) study may be required in the future if the use profile is 

expanded. However, the TTR study requirement is currently waived for azoxystrobin (TXR# 

0056307). 

Table 6.2. Highest Residential Post-Application Non-Cancer Exposure and Risk Estimates for 

Azoxystrobin.

Lifestage Post-Application Exposure Scenario Dose MOEs

Adult Indoor Inhalation 0.00000000011 220,000,000,000

Child

Inhalation 0.00000000087 52,000,000,000

Indoor Carpet - Broadcast Hand to Mouth 0.098 250

6.3 Combined Exposure

FQPA requires residential exposures that could reasonably be expected to occur on the same day 

to be combined and compared to the appropriate toxicity endpoint. In general, residential 

handler and post-application scenarios generally should not be combined. Additionally, no 

dermal endpoint was chosen for azoxystrobin and outdoor inhalation post-application exposure is 

considered negligible. Therefore, residential post-application exposure scenarios for 

azoxystrobin were not combined. 

6.4 Residential Bystander Post-Application Inhalation Exposure

Although a quantitative residential post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for residential handlers. This 

exposure scenario is representative of a worse case inhalation exposure and should be considered 

protective of most post-application inhalation exposure scenarios.

6.5 Spray Drift

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

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

potential source of exposure from the ground application method employed for azoxystrobin. 

The Agency has been working with the Spray Drift Task Force, EPA Regional Offices and State 

Lead Agencies for pesticide regulation and other parties to develop the best spray drift 

management practices (see the Agency’s Spray Drift website for more information at 

http://www.epa.gov/opp00001/factsheets/spraydrift.htm). On a chemical by chemical basis, the 

Agency is now requiring interim mitigation measures for aerial applications that must be placed 
Azoxystrobin Human Health Risk Assessment DP No. 402285

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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 with specific products with significant risks 

associated with drift.

7.0 Aggregate Exposure/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 azoxystrobin, potential exposures from food, drinking water and 

residential scenarios were aggregated. 

This assessment has considered the changes in the new Residential Standard Operating 

Procedures (SOPs) implemented in January of 2012. HED confirms that there are no risks of 

concern resulting from the proposed uses, nor from utilizing the new Residential SOPs to 

estimate residential exposure and risk.

7.1 Acute Aggregate Risk

The aggregate acute risk estimates include exposure to residues of azoxystrobin in food and 

water, and do not include dermal, inhalation, or incidental oral exposure. The acute risk estimate 

for the U.S. population and all other population subgroups, resulting from aggregate exposure to 

azoxystrobin in food and drinking water, is below the Agency’s LOC. The food and drinking 

water exposure estimates are 17% of the aPAD for the general U.S. population, and 41% for the 

most highly exposed subgroup, children 1-2 years old. 

7.2 Short-Term Aggregate Risk

There is potential short-term exposure to azoxystrobin via dietary (which is considered 

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

adults, these pathways lead to exposure via oral (background) as well as dermal and inhalation 

(primary) routes. The most conservative scenario was chosen for each population (e.g., hand-tomouth exposure from carpets and textiles for children 1-2 years old). For a description of the 

residential exposure scenarios considered in the aggregate assessment, see Section 6.0.

The general US population (inhalation) aggregate MOE is 920. Therefore, adult aggregate

exposure and risk does not exceed HED’s LOC (MOE <100). The aggregate MOE for children 

1-2 years old, including incidental oral exposures from treated carpets, is 190, which indicates 

that aggregate exposure and risk is greater than HED’s LOC (MOE<100). Further refinement 
Azoxystrobin Human Health Risk Assessment DP No. 402285

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using additional % CT estimates or more refined EDWCs may need to be incorporated in future 

assessments. 

Table 7.2. Short-Term Aggregate Risk Calculations.

Population & 

Activity

NOAEL 

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food and 

Water 

Exposure 

mg/kg/day

Residential 

Exposure 

mg/kg/day3

Total 

Exposure 

mg/kg/day4

Aggregate 

MOE (food, 

water and 

residential)5

General U.S. 

Population 25 100 1 0.012290 0.0149 0.02719 920

Children 1-2

years

25 100 1 0.031142 0.0982 0.129342 190

1. LOC includes standard inter- (10X) and intra- (10X) species uncertainty factors totaling 100.

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

3. Residential Exposure = [Oral exposure + Inhalation Exposure]. Source of residential exposure values used in aggregate 

assessment (Table 6.1 and Table 6.2). Exposure estimate for Children 1-2 years includes post-application inhalation exposure 

(0.00000000087 mg/kg/day)+ incidental oral ingestion from treating carpets (0.0982 mg/kg/day) = 0.098 mg/kg/day. 

4. Total Exposure = Avg Food & Water Exposure + Residential Exposure)

5. Aggregate MOE OAEL=25 mg/kg/day.

7.3 Intermediate-Term Aggregate Risk

Intermediate-term exposure is not expected for the adult residential (inhalation) exposure 

pathway. Therefore, the intermediate-term aggregate risk would be equivalent to the chronic 

dietary exposure estimate. In the previous risk assessment, both short- and intermediate-term 

incidental oral residential risks were included in the aggregate risk assessment for azoxystrobin 

(K. Rury, D389702, 1/18/2012). Based on the azoxystrobin use pattern, and the 2012 Revised 

Residential SOPs (2012), only short-term residential handler and post-application exposures 

should be included in the aggregate risk assessment. 

7.4 Chronic Aggregate Risk

Chronic exposure is not expected for the adult residential (dermal and inhalation) exposure 

pathway. Therefore, the chronic aggregate risk would be equivalent to the chronic dietary 

exposure estimate. Refer to Section 5.4.3 for the chronic dietary (food and drinking water) 

exposure assessment. 

7.5 Cancer Aggregate Risk

Azoxystrobin is considered “not likely to be carcinogenic to humans;” therefore, an aggregate 

cancer risk assessment has not been conducted. 

8.0 Cumulative Exposure/Risk Characterization

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 azoxystrobin and any other substances and azoxystrobin does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, therefore, 

EPA has not assumed that azoxystrobin has a common mechanism of toxicity with other 
Azoxystrobin Human Health Risk Assessment DP No. 402285

Page 32 of 42

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/.

9.0 Occupational Exposure/Risk Characterization

References:

- Azoxystrobin. Occupational and Residential Exposure Assessment to Evaluate the Risk from Proposed Uses on 

Sugarcane, K. Rury, DP#394287, 03/30/2012.

9.1 Short-/Intermediate-Term Handler Risk

Azoxystrobin is proposed for use as a foliar application to cereal grains. Application methods, 

maximum application rates and use sites are summarized in Table 9.1. Based on the proposed 

use pattern of azoxystrobin, there is a potential for short- and intermediate-term occupational 

exposure during handling (mixing, loading, flagging, and applying). Chronic exposure is not 

expected for the proposed use patterns. PPE was assessed at baseline (long pants, a long-sleeved 

shirt, shoes, socks, no chemical-resistant gloves, and no respirator). The Quilt Xcel®, Quilt® 

and Abound® require handlers to wear long sleeved shirts, long pants, chemical resistant gloves, 

shoes, and socks. Quilt Xcel® and Quilt® also require the use of protective eyewear.

The results of the occupational handler exposure and risk assessment estimates indicate that 

short- and intermediate-term inhalation MOEs are not of concern to HED (i.e. MOEs > 100) with 

baseline mitigation (no respirator). The short-term inhalation MOEs range from 38,000 to 

570,000 for occupational handlers. The intermediate-term MOEs range from 30,000 to 460,000 

for occupational handlers (Table 9.1).

The Agency has evaluated scenarios that may be limited in nature such as flagging during aerial 

applications because engineering controls (i.e., Global Positioning Satellite technology) are now 

predominantly used as indicated by the 1998 National Agricultural Aviation Association 

(NAAA) survey of their membership. It appears, however, that flaggers are still used in 

approximately 10 to 15 percent of aerial application operations. In cases like these, the Agency 

strongly encourages the use of the engineering control system but will continue to evaluate risks 

for flaggers and any other population where a clear exposure pathway exists until the potential 

for exposure is eliminated. The Agency is aware that NAAA is conducting another survey on 

exposure issues and will consider those results as they are timely and appropriate.

HED has no data to assess exposures to pilots using open cockpits. The only data available is for 

exposure to pilots in enclosed cockpits. Therefore, risks to pilots are assessed using the 

engineering control (enclosed cockpits) and baseline attire (long-sleeve shirt, long pants, shoes, 

and socks); pilots are not required to wear protective gloves. With this level of protection, there 

are no risk estimates of concern for applicators.
Azoxystrobin Human Health Risk Assessment DP No. 402285

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Table 9.1. Short- and Intermediate-Term Occupational Exposure and Risk Estimates for Proposed Use of 

Azoxystrobin on Cereal Grains (Barley, Oats, Rye, Wheat, and Triticale). All estimates are at baseline 

mitigation (single layer without gloves or respiratory protection). 

Exposure Scenario Crop(s)

Baseline 

Inhalation 

Unit 

Exposure 

(μg/lb ai)1

Maximum

Applicatio

n Rate (lb 

ai/A)2

Area 

Treated or 

Amount 

Handled 

Daily3

Inhalation

Dose 

(mg/kg/day)4

Short-Term 

MOE5

IntermediateTerm MOE6

Mixer/Loader

Mixing/Loading Liquids 

for Groundboom 

Application

Barley, Oats, 

Rye

0.219 0.20

80 0.000044 570,000 460,000

Wheat, 

Triticale 200 0.00011 230,000 180,000

Mixing/Loading Liquids 

for Aerial and 

Chemigation Application

Barley, Oats, 

Rye 350 0.00019 130,000 100,000

Wheat, 

Triticale 1200 0.00066 38,000 30,000

Flagger

Flagging for

Aerial Application

Barley, Oats, 

Rye, Wheat, 

Triticale

0.35 0.20 350 0.00031 82,000 65,000

Applicator

Applying Sprays via 

Groundboom Equipment

Barley, Oats, 

Rye

0.34

0.20

80 0.000068 370,000 290,000

Wheat, 

Triticale 200 0.00017 150,000 120,000

Applying Sprays via

Aerial Equipment *

Barley, Oats, 

Rye

0.068

350 0.000060 420,000 340,000

Wheat, 

Triticale 1200 0.00020 120,000 98,000

1 Based on “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2012); includes data from 

PHED /AHETF. Level of mitigation: Baseline.

2 Based on registered labels with proposed new uses (Reg. Nos. 100-1098, 100-1178, 100-1324).

3 Exposure Science Advisory Council Policy #9.1.

4 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × 

Area Treated Daily (A/day) ÷ BW (kg). Bodyweight = 80 kg.

5 Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). Short-Term Inhalation NOAEL = 25 

mg/kg/day.

6 Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). Intermediate-Term Inhalation NOAEL = 20 

mg/kg/day.

9.2 Short-/Intermediate-Term Post-Application Risk

9.2.1 Dermal Post-Application Risk

The proposed occupational uses for azoxystrobin addressed in this document result in the 

potential for exposure to azoxystrobin during scouting, hand weeding, and hand harvesting. 

However, no appropriate dermal endpoint was identified for azoxystrobin. Therefore, an 

assessment of occupational dermal post-application exposure to azoxystrobin was not conducted. 

A chemical-specific dislodgeable foliar residue (DFR) study is available for the use of 
Azoxystrobin Human Health Risk Assessment DP No. 402285

Page 34 of 42

azoxystrobin on grapes, but has not been employed in this or previous risk assessments because 

HED determined there is no hazard via the dermal route. 

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for azoxystrobin at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category III), low vapor pressure (8.2x10-13 mm Hg at 20oC), and 

the low proposed use rate (0.20 lb ai/A). However, there are multiple potential sources of postapplication inhalation exposure to individuals performing post-application activities in 

previously treated fields. These potential sources include volatilization of pesticides and 

resuspension of dusts and/or particulates that contain pesticides. 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, and 

received the SAP’s final report on March 2, 20101. The Agency is in the process of evaluating

the SAP report as well as available post-application inhalation exposure data generated by the 

ARTF and may, as appropriate, develop policies and procedures, to identify the need for and, 

subsequently, the way to incorporate occupational post-application inhalation exposure into the 

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

revisit the need for a quantitative occupational post-application inhalation exposure assessment 

for azoxystrobin.

Although a quantitative occupational post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios.

Nevertheless, per the Worker Protection Standard (WPS), a 12-hour restricted entry interval 

(REI) is required for chemicals classified under Toxicity Category III or IV. Azoxystrobin is 

classified as Toxicity Category III for acute dermal and primary eye irritation and Toxicity 

Category IV for primary skin irritation. Even though a 12-hour REI usually is the shortest 

waiting period permitted under the WPS, REIs may be further reduced from 12 hours if certain 

criteria are met for both the technical material and the different end-use products in accordance 

with the Pesticide Registration (PR) Notice 95-3 [Reduction of Worker protection Standard 

(WPS) Interim Restricted Entry Intervals (REIs) for Certain Low Risk Pesticides]. Previously, 

HED determined that the criteria for the technical material had been met for azoxystrobin, and 

RD had determined the criteria for the end-use products Abound®had been met, and therefore, 

the 4-hour REI, as listed on the label, is acceptable for Abound®. It should be noted that the REI 

of 12 hours listed on the multiple ai products Quilt Xcel® and Quilt ® with both azoxystrobin 

and propiconazole, is acceptable under the WPS. 

10.0 References

J. Wolf, 01/06/2010, DP#371383, Drinking Water Assessment for amended label Quadris TopTM 

fungicide (EPA Reg. No. 100-1313) Azoxystrobin for use on golf course turf (only). 

 

1 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
Azoxystrobin Human Health Risk Assessment DP No. 402285

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I. Abdel-Saheb, 07/25/2012, DP#400772, Drinking Water Exposure Assessment for new use of 

azoxystrobin on oat and rye.

N. Tsaur, 10/09/2012, DP#402288, Occupational and Residential Exposure 

Assessment for a Proposed Use on Cereal Grains (Barley, Oats, Rye, Wheat, and Triticale).

M. Negussie, 09/25/2012, DP#402287, Acute and Chronic Aggregate Dietary (Food and 

Drinking Water) Exposure and Risk Assessments for Section 3 Petitions for the Establishment of 

Tolerances on Ginseng (import, PP#1E7945); Rye and Oats (PP#2F7976), and Section 3 

Amendments to Revise the Established Tolerances on Cereal Grains (Barley and Wheat) Due to 

Changes of Pre-Harvest Intervals (PP# 2F7984).

M. Negussie, 10/11/2012, DP#397692, Section 3 Petitions for the Establishment of Tolerances 

on Ginseng (import, PP#1E7945), Rye, and Oats (PP#2F7976), and Section 3 Amendments to 

Revise the Established Tolerances on Cereal Grains (Barley and Wheat) Due to Changes of PreHarvest Intervals (PP# 2F7984). Summary of Analytical Chemistry and Residue Data
Azoxystrobin Human Health Risk Assessment DP No. 402285

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Appendix A. Toxicology Profile 

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.500) for non-food use for azoxystrobin are in Table 1. Use of the new guideline 

numbers does not imply that the new (1998) guideline protocols were used.

Study

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

no

CR1

yes

yes

yes

no

yes*

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

yes

yes

yes

yes

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

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

870.5375 Mutagenicity—Structural Chromosomal Aberrations...

870.5385 Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

yes

yes

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

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

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

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

870.6300 Develop. Neurotoxicity .................................................

no

no

yes

yes

no

-

-

yes

yes

no

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

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

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

yes

no

yes

yes

yes

no

Special Studies for Ocular Effects

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

Subchronic Oral (rat) ..................................................

Six-month Oral (dog)..................................................

yes

no

yes

-

-

-

1CR = Conditionally Required

* The requirement for a subchronic inhalation toxicity study has been waived (TXR#0056307)
Azoxystrobin Human Health Risk Assessment DP No. 402285

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A.2 Toxicity Profiles

Table A.2.1. Acute Toxicity Data on Technical Azoxystrobin. 

Guideline

No. Study Type MRID # Results

Toxicity 

Category

870.1100 Acute Oral - Rat 43678122 LD50 > 5000 mg/kg (Limit Test) in Males & 

Females

IV

870.1200 Acute Dermal -

Rat

43678124 LD50 > 2000 mg/kg (Limit Test) in Males & 

Females

III

870.1300 Acute Inhalation -

Rat

43678126 LC50 Males = 0.962 mg/L (95% C.I. = 0.674)

Females = 0.698 mg/L (95% C.I. = 0.509, 2.425)

The combined LC50 was not calculated

due to mortality pattern

III

870.2400 Primary Eye 

Irritation - Rabbit

43678128 Slight to moderate erythema and slight chemosis in 

all rabbits within one hour, but effects resolved 

within 48 hours of treatment.

III

870.2500 Primary Skin 

Irritation - Rabbit

43678130 Very slight erythema and edema that persisted for 

three days on one rabbit and for one hour on 

another.

IV

870.2600 Dermal 

Sensitization -

Guinea Pig

43678132 No erythema or edema were found 38 or 48 hrs 

after challenge with test material.

Not a 

dermal 

sensitizer

Table A.2.2. Azoxystrobin Toxicity Results From Repeated Dosing and Other Studies.

Study Guideline/Study MRID Results

870.3100

90-Day oral toxicity in 

rats

43678135 (1992) 

Acceptable/guideline

0, 200, 2000, 4000 ppm

M: 0, 20.4, 211.0, 443.8 

mg/kg/day

F: 0, 22.4, 223.0, 448.6 

mg/kg/day

NOAEL = 20 mg/kg/day

LOAEL = 211 mg/kg/day based on decreased weight 

gain in both sexes, clinical observations of distended 

abdomens and reduced body size, and clinical 

pathology findings attributable to reduced nutritional 

status.

870.3150

90-Day oral toxicity in 

dogs

43678136 (1993)

Acceptable/guideline

M & F: 0, 10, 50, 250 

mg/kg/day 

NOAEL = 50 mg/kg/day

LOAEL = 250 mg/kg/day based on treatment-related 

clinical observations and clinical chemistry 

alterations indicative of effects on liver/biliary 

function in both sexes.

870.3200

21-Day dermal toxicity in 

rats

43678137 (1994)

Acceptable/guideline

M & F: 0, 200, 500, 1000

NOAEL = 1000 mg/kg/day (limit dose)

LOAEL > 1000 mg/kg/day.

870.3700a

Prenatal developmental in 

rats

43678142 (1994)

Acceptable/guideline

0, 25, 100, 300 mg/kg/day

Maternal NOAEL = 25 mg/kg/day

LOAEL = 100 mg/kg/day based on the maternal 

clinical signs of increased diarrhea, urinary 

incontinence, and salivation.

Developmental NOAEL = 100 mg/kg/day

LOAEL > 100 mg/kg/day.

870.3700b

Prenatal developmental in 

rabbits

44058701 (1995)

Acceptable/guideline

0, 50, 150, 500 mg/kg/day

Maternal NOAEL = 150 mg/kg/day

LOAEL = 500 mg/kg/day based on decreased body 

weight gain.

Developmental NOAEL = 500 mg/kg/day

LOAEL > 500 mg/kg/day.

870.3800

Reproduction and fertility 

43678144 (1994)

Acceptable/guideline

Parental/Systemic NOAEL = 32 mg/kg/day

LOAEL = 165 mg/kg/day based on reduced body 
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Table A.2.2. Azoxystrobin Toxicity Results From Repeated Dosing and Other Studies.

Study Guideline/Study MRID Results

effects in rats 0, 60, 300, 1500 ppm

M: 0, 6.4, 32.3, 165.4 

mg/kg/day

F: 0, 6.8, 33.8, 175.0 

mg/kg/day

weight, reduced food consumption, and increased 

adjusted liver weights in both sexes in addition to 

gross and histopathologic lesions of the bile duct and 

liver in males.

Reproductive NOAEL = 165 mg/kg/day

LOAEL > 165 mg/kg/day.

Offspring NOAEL = 32 mg/kg/day

LOAEL = 165 mg/kg/day based on reduced pup 

body weight and increased adjusted liver weights.

870.4100

Chronic toxicity in dogs

43678140 (1994)

Acceptable/guideline

0, 3, 25, 200 mg/kg/day

NOAEL = 25 mg/kg/day

LOAEL = 200 mg/kg/day based, in both sexes, on

clinical observations, increased liver weight, and 

clinical chemistry changes indicative of effects on 

liver/biliary function.

870.4200

Carcinogenicity in mice

43678141 (1995)

Acceptable/guideline

0, 50, 300, 2000 ppm

M: 0, 6.2, 37.5, 272.4 

mg/kg/day

F: 0, 8.5, 51.3, 363.3 

mg/kg/day

NOAEL = 38 mg/kg/day

LOAEL = 272 mg/kg/day based on reduced body 

weights in both sexes.

There was no evidence of carcinogenicity.

870.4300

Combined Chronic 

toxicity/ Carcinogenicity 

in rats

43678139 (1995)

Acceptable/guideline

0, 60, 300, &1500/750 ppm 

for males (due to excessive 

death the high dose was 

reduced beginning at week 

52-104)

For females: 0, 60, 300,& 

1500 ppm

M: 0, 3.6, 18.2, 82.4 

mg/kg/day

F: 0, 4.5, 22.3, 117.1 

mg/kg/day

NOAEL = 18 mg/kg/day

LOAEL = 82.4 mg/kg/day in males and 117 

mg/kg/day in females based on reduced body 

weights in both sexes and bile duct lesions in males.

There was no evidence of carcinogenicity.

870.5100

Bacterial reverse gene 

mutation

43668146 (1992)

Acceptable/guideline

100, 200, 500, 1000, 2500, 

5000 μg/plate

Negative in increasing revertant colonies up to 5000 

μg/plate +/-S9 using both plate incorporation and 

preincubation protocols and Salmonella strains 

TA98, TA100, TA1535, and TA1537 as well as the 

E. Coli strains WP2P and WP2PuvrA. Cytotoxicity 

and compound precipitation were seen at the high 

dose.

870.5300

Mammalian cell forward 

gene mutation (mouse 

lymphoma cells)

43678145 (1993)

Acceptable/guideline

8 to 80 μg/mL in three 

assays

Nonlinear, slight but significant increases in the 

mutation frequency (MF) of mouse lymphoma 

L5178Y TK+/-at 15-60 μg/mL +/-S9. Despite the 

absence of a dose response, increased MFs were 

reproducible; therefore, Azoxystrobin is considered 

positive in this test system. Colony sizing was not 

performed.

870.5375

Cytogenetics 

chromosomal aberration 

43678147 (1992)

Acceptable/guideline

0.5 to 50 μg/mL without S9 1 to 300 μg/mL with S-9

The in vitro test in human lymphocytes was positive

for the induction of chromosomal aberrations in both 

the presence and absence of S9 at doses (5-50 μg/mL 

-S9; 100-200 μg/mL +S9) that were moderately to 

severely cytotoxic (i.e. >16-70% reductions in 
Azoxystrobin Human Health Risk Assessment DP No. 402285

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Table A.2.2. Azoxystrobin Toxicity Results From Repeated Dosing and Other Studies.

Study Guideline/Study MRID Results

mitotic cells, respectively)

870.5385 

Cytogenetics bone 

marrow

43678148 (1992)

Acceptable/guideline

5000 

mg/kg

The in vivo mouse bone marrow micronucleus assay 

was negative at 5000 mg/kg when administered once 

by oral gavage. Overt toxicity and depression of 

erythropoiesis seen in addition to cytotoxic effects on 

the target cell in the males. 

870.5550

Other: Unscheduled DNA 

synthesis

43678149 (1992)

Acceptable/guideline

1250 and 2000 mg/kg

The in vivo/in vitro unscheduled DNA synthesis test 

in rat hepatocytes was negative. No toxicity to the 

treated animals or cytotoxic effects on recovered 

hepatocytes up to the limit dose for acute testing 

(2000 mg/kg) when administered once by oral 

gavage.

870.6200a

Acute neurotoxicity 

screening battery in rats

43678134 (1994)

Acceptable/guideline

0, 200, 600, 2000 mg/kg

NOAEL < 200 mg/kg/day

LOAEL = 200 mg/kg/day based on transient diarrhea 

in both sexes. 

870.6200b

Subchronic neurotoxicity 

screening battery in rats

43678138 (1994)

Acceptable/guideline

0, 100, 500, 2000 ppm

M: 0, 8.0, 38.5, 161 

mg/kg/day 

F: 0, 9.1, 47.9, 201.5 

mg/kg/d

NOAEL = 39 mg/kg/day.

LOAEL = 161 mg/kg/day based on decreased body 

weight/weight gain and food utilization in both 

sexes.

870.7485

Metabolism and 

pharmacokinetics

43678150 

43678151

43678152 

43678153

43678154

1 or 100 mg/kg (single 

gavage) or 1 mg/kg (14-

day repeated)

Following oral administration as a single gavage 

dose of 1 or 100 mg/kg or 15-day repeated doses of 1 

mg/kg, azoxystrobin was widely distributed with the 

liver and kidneys having the highest concentrations; 

however, less than 0.5% of the administered dose 

was detected in the tissues at seven days postdosing. 

The primary route of excretion was via the feces 

(≈73-89%) followed by urine (≈9-18%). There were 

no apparent sex- or dose-related differences in 

distribution or in the pattern of excretion. In a bile 

duct cannulated single high-dose group, assessment 

of biliary excretion suggested approximately 70% 

absorption with ≈32% of the administered dose 

remaining as parent compound in the gastrointestinal 

tract. Absorbed azoxystrobin appeared to be 

extensively metabolized with minor sex-related 

qualitative and quantitative differences in biliary 

metabolites. A metabolic pathway was proposed 

showing hydrolysis and subsequent glucuronide 

conjugation as the major biotransformation process.

870.7600

Dermal penetration (rat)

43678155 (1994)

Acceptable/guideline

0.01, 0.1, 0.9, 13.3 mg/kg

2 - 4 % Dermal Absorption 
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Appendix B. Physical/Chemical Properties

Table B. Physicochemical Properties of Technical Grade Azoxystrobin.

Parameter Value Reference

Melting point/range 114-116oC DP#s 218318 and 218448, 

3/19/96, J. Garbus pH 6.4

Density 1.25 g/cm3

Water solubility (20°C) pH 5.2 6.7 mg/L

pH 7.0 6.7 mg/L

pH 9.2 5.9 mg/L

Solvent solubility (20°C) Hexane 0.057 mg/L

Octanol 1.4 mg/L

Methanol 20 mg/L

Toluene 55 mg/L

Acetone 86 mg/L

Ethyl Acetate 130 mg/L

Acetonitrile 340 mg/L

Dichloromethane 400 mg/L

Vapor pressure (20°C) 1.1x10-13 kPa (8.2x10-13 mm Hg)

Dissociation constant, pKa Not dissociable

Octanol/water partition coefficient, 

Log(KOW)

log P = 2.5

UV/visible absorption spectrum Not available
Azoxystrobin Human Health Risk Assessment DP No. 402285

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Appendix C. International Residue Limit Status Sheet.

Azoxystrobin (PC Code 128810; 08/22/12)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition: 

US Canada Mexico2 Codex3

40 CFR 180.507:

Plant: sum of azoxystrobin, 

[methyl( E )-2-(2-(6-(2-

cyanophenoxy) pyrimidin-4-

yloxy)phenyl)-3-

methoxyacrylate], and the Zisomer of azoxystrobin [methyl( Z 

)-2-(2-(6-(2-

cyanophenoxy)pyrimidin-4-

yloxy)phenyl)-3 methoxyacrylate] 

(αE)-methyl 2-[[6-(2-

cyanophenoxy)-4-

pyrimidinyl]oxy]-α -

methoxymethylene)benzene

acetate,

including the isomer (Z)-

methyl 2-[[6-(2-

cyanophenoxy)-4-

pyrimidinyl]oxy]--

(methoxymethylene)benzen

eacetate

Azoxystrobin.

The residue is fat 

soluble. 

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex3

Ginseng 0.5 0.5 ginseng roots 0.1 Ginseng

0.5 Ginseng, dried

0.5 ginseng, processed 

products (both 

proposed)

Oat, forage 5

Oat, hay 10

Oat, straw 3 15 straw and fodder of 

cereal grains

Oat, grain 1.5 0.03 0.5

Rye, forage 7

Rye, straw 1.5 15 straw and fodder of 

cereal grains

Rye, grain 0.2 0.03 0.2

Barley, hay 10

Barley, straw 15 15 straw and fodder of 

cereal grains

Barley, grain 3 0.03 0.5

Wheat, forage 15

Wheat, straw 10 15 straw and fodder of 

cereal grains

Wheat, hay 30

Wheat, grain 0.2 0.03 0.2

Grain, aspirated grain 

fractions*

420

Completed: M. Negussie; 08/31/2012

1

Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and 

not those proposed by the applicant. *The established tolerance should remain at 420 ppm. 

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.
Azoxystrobin Human Health Risk Assessment DP No. 402285

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3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.

Appendix D. Review of Human Research

Studies reviewed for ethical conduct:

The PHED Task Force, 1995. The Pesticide Handlers Exposure Database, Version 1.1. 

Electronic Database. Task Force members Health Canada, U. S. Environmental Protection 

Agency, and the National Agricultural Chemicals Association, released February, 1995.

The Agricultural Handler Exposure Task Force (AHETF), 2011. The Occupational Handler 

Unit Exposure Surrogate Reference Table. U.S. Environmental Protection Agency. Released 

June 21, 2011. 

Data from the Outdoor Residential Exposure Task Force (ORETF).