Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 3 of 52

5.1.4 Residues of Concern Summary............................................................................ 23

5.2 Food Residue Profile .................................................................................................... 24

5.3 Water Residue Profile.................................................................................................. 26

5.4 Dietary Risk Assessment.............................................................................................. 27

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

Assessment........................................................................................................................... 27

5.4.2 Acute Dietary Risk Assessment ........................................................................... 27

5.4.3 Chronic Dietary Risk Assessment ....................................................................... 27

5.4.4 Summary Table..................................................................................................... 28

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 28

6.1 Residential Handler Exposure .................................................................................... 28

6.2 Post-Application Exposure .......................................................................................... 29

6.3 Combined Exposure..................................................................................................... 30

6.4 Residential Bystander Post-application Inhalation Exposure ................................. 30

6.5 Spray Drift.................................................................................................................... 31

7.0 Aggregate Exposure/Risk Characterization.................................................................. 31

7.1 Acute Aggregate Risk................................................................................................... 31

7.2 Short-Term Aggregate Risk ........................................................................................ 32

7.3 Intermediate-Term Aggregate Risk ........................................................................... 32

7.4 Chronic Aggregate Risk .............................................................................................. 33

7.5 Cancer Aggregate Risk ................................................................................................ 33

8.0 Cumulative Exposure/Risk Characterization ............................................................... 33

9.0 Occupational Exposure/Risk Characterization ............................................................ 33

9.1 Short-/Intermediate-Term Handler Risk................................................................... 34

9.2 Short-/Intermediate-Term Post-Application Risk .................................................... 35

9.2.1 Dermal Post-Application Risk ............................................................................. 35

10.0 References......................................................................................................................... 36

Appendix A. Toxicology Profile................................................................................................ 37

A.1 Toxicology Data Requirements................................................................................... 37

A.2 Toxicity Profiles............................................................................................................ 38

Appendix B. Physical/Chemical Properties............................................................................. 41

Appendix C. International Residue Limit Status Sheet. ........................................................ 42

Appendix D. Azoxystrobin Metabolites................................................................................... 44

Appendix E. Review of Human Research................................................................................ 50
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 4 of 52

1.0 Executive Summary

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

methoxyacrylate] is a broad spectrum fungicide that controls plant diseases on agricultural crops, 

turf and ornamentals, and controls 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. 

The Rutger’s University Interregional Research Project No. 4 (IR-4) has proposed azoxystrobin 

for use on post-harvest tuberous and corm vegetables (subgroup 1C), and as a field application to 

dragon fruit and wasabi. IR-4 also requested the use profile of azoxystrobin be updated to 

incorporate the recent 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. The most recent human health risk assessment 

was conducted for a Special Local Need (Section 24c) use on tobacco in greenhouses (W. 

Cutchin, D368146, 09/14/2009). Since the last risk assessment, no additional hazard data have 

been submitted. HED also recently conducted a human health assessment scoping document in 

support of Registration Review (B. O’Keefe, D365660, 12/07/2009). An immunotoxicity study 

is required for azoxystrobin under 40 CFR §158.500. 

Use Profile

Azoxystrobin is proposed for use as a foliar application on wasabi using ground and chemigation 

equipment. Wasabi is typically grown in greenhouses in the United States. Azoxystrobin is also 

proposed for use as a foliar application to dragon fruit using ground, aerial and chemigation 

equipment. Azoxystrobin is also proposed for post-harvest use using T-jet, controlled droplet 

application (CDA) or similar application methods. Applications to post-harvest tuberous and 

corm vegetables (subgroup 1C) may be made by mixing 0.6 fl oz Abound® with 0.5 gallons 

water and applying to one ton of tubers (2,000 lbs). The full use profile for azoxystrobin is 

shown in Section 3.3.

Toxicity/Hazard

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

database, with the exception of an immunotoxicity study. 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. 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. 

The Food Quality Protection Act (FQPA) safety factor (SF) for azoxystrobin was retained at 3X 

to account for using a lowest observed adverse effect level (LOAEL) to extrapolate to a no 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 5 of 52

observed adverse effect level (NOAEL) for the acute dietary exposure point of departure (PoD). 

NOAELs were used for short-term, intermediate-term, and chronic risk assessments. Although 

an immunotoxicity study is needed to complete the toxicological database, the selected toxicity 

endpoints and PoDs for risk assessment are based on the most sensitive and relevant data. 

Currently, there are no concerns for structural immunotoxicity based on the results of existing 

studies. 

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. 

Estimated drinking water concentrations (EDWCs) were incorporated directly into the dietary 

exposure assessments. 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-FCIDTM) 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 (<100% of the acute population adjusted dose (aPAD)) for all population subgroups and

were estimated at 18% of the aPAD for the U.S. general population and 42% of the aPAD for the 

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

dietary assessment using tolerance-level residues, average % CT estimates and default DEEMFCIDTM processing factors was also conducted. The results of the chronic dietary analysis for 

food and drinking water indicate that the chronic dietary risk estimates are below the Agency’s 

level of concern (<100% of the chronic population adjusted dose (cPAD)) for all population 

subgroups and were estimated at 7% of the cPAD for the U.S. general population and 16% 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

Residential exposures were not assessed in this document because the proposed uses of 

azoxystrobin do not involve applications by homeowners or commercial applicators to 

residential settings. 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 assessed in a previous document (S. Piper, D344389, 4/30/2008).

Occupational Exposure

Short- and intermediate-term dermal and inhalation exposure is expected for occupational 

handlers. HED the proposed uses and requested changes to the azoxystrobin crop group 

tolerances and determined that an occupational exposure assessment is needed only for the postharvest tuberous and corm (subgroup 1C) use. The new uses, and the uses included in the 

revised crop groups have either been adequately assessed by HEd or are expected to result in 

lower exposures than uses previously assessed. The results of the occupational handler exposure 

and risk assessment estimates indicate that total short- and intermediate-term margins of 

exposure (MOEs) are not of concern to HED (i.e. MOE > 100) with baseline attire. Although 

occupational dermal exposure is expected following treatment of post-harvest tuberous and corm 

vegetables (subgroup p1C), no dermal hazard was identified for azoxystrobin. Therefore, a 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 6 of 52

quantitative post-application dermal risk assessment was not conducted. HED assumes that postapplication inhalation exposures are minimal following applications of an active ingredient (ai)

with low vapor pressure (<1.0x10-7 mm Hg). Since azoxystrobin has low acute inhalation 

toxicity (Toxicity Category III) and a low vapor pressure (8.2x10-13 mm Hg), post-application 

inhalation exposures and risks were not quantitatively assessed. 

Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These studies (Appendix E) have been 

determined to require a review of their ethical conduct, and one of these studies is also subject to 

review by the Human Studies Review Board. All of the listed studies have received the 

appropriate review.

2.0 HED Recommendations

HED recommends the registration request be conditionally granted for azoxystrobin use on postharvest tuberous and corm vegetables (subgroup 1C), and as field applications to dragon fruit 

and wasabi. HED also recommends that the use profile of azoxystrobin be updated to 

incorporate the recent 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, with the tolerance revisions requested in Section 

2.2.3. 

2.1 Data Deficiencies/Prior Conditions of Registration

The following data are required as conditions of registration: 

870.7800 Immunotoxicity Study

The registrant must submit an immunotoxicity study. Syngenta has estimated the 

immunotoxicity study will be completed in November 2011. The immunotoxicity study 

remains a condition of registration for azoxystrobin under Registration Review and is due 

in 2012.

The following data should be submitted with future uses:

875.2100 Foliar Dislodgable Residue Dissipation

Turf transferable residue (TTR), studies may be required in the future if the use profile is 

expanded.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 7 of 52

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

There are Canadian and Codex Maximum Residue Limits (MRLs) for residues of azoxystrobin 

and its Z-isomer for most of the requested crops. The Codex MRLs (JMPR Report 2008) are 

based on US field trials, except for subgroup 8-10A and 8-10B which were conducted in Europe. 

Even though the Codex MRLs are based predominately on US field trials, there is a slight 

difference between MRLs of Codex/US due in part to the difference in residue definition. The 

US residue definition includes both the predominant E-isomer and the minor Z-isomer. The 

Codex residue definition includes only the E-isomer. The difference in Codex and US MRL 

estimates, based on the same data set, is based on the JMPR rounding procedures and the 

tendency to increase the estimate for small data sets. 

The US tolerances and Codex MRLs are harmonized for caneberry subgroup 13-07A; 

strawberries; and sunflower subgroup 20B. The US and Codex MRLs are not harmonized for 

low growing berry subgroup 13-07G; dragon-fruit (mango); onion, bulb and green (subgroups 3-

07A & B); vegetable, fruiting, subgroup 8-10A; tuberous and corm vegetables (subgroup 1C);

and wasabi (herbs, fresh and dry).

HED recommends increasing the US MRLs for bushberry, subgroup 13-07B; cottonseed, 

subgroup 20C; fruit, citrus, group 10-10; small fruit vine climbing 13-07F [grape]; and 

vegetable, fruiting, subgroup 8-10B to harmonize with Codex.

The US tolerances and Canadian MRLs are in harmony on all proposed crops, except subgroup 

13-07F, 13-07G, cottonseed, and for the proposed tuberous and corm vegetables subgroup 1C. 

There are no Canadian MRLs on cotton seed. Canadian MRLs were not established as 

subgroups for 13-07F and 13-07G and were established on grapes (3 ppm) and lowbush 

blueberries and lingonberries (subgroup 13-07B) at 3ppm; US MRLs were established at 1ppm 

for 13-07F and at 10 ppm for 13-07G. Based on the Organization for Economic Cooperation and 

Development (OECD) calculation procedures for the current post-harvest potato data, HED

recommends increasing the US tolerances for vegetable tuberous and corm, subgroup 1C to 8 

ppm, which is in agreement with the proposed Canadian MRL.

2.2.3 Recommended Tolerances 

Pending submission of a revised Section F, there are no residue chemistry issues that will 

preclude establishment of permanent tolerances for azoxystrobin in/on the following crops or 

crop groups/subgroups:

Table 2.2.3. Tolerance Summary for Azoxystrobin
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 8 of 52

Commodity Established 

Tolerance (ppm)

Proposed 

Tolerance 

(ppm)

Recommended 

Tolerance (ppm)

Comments; Correct 

Commodity Definition

Onion, bulb, subgroup 3-07A Onion, bulb 1.0 1.0 1.0

Onion, green, subgroup 3-07B Onion, green 7.5 7.5 7.5

Vegetable, fruiting, subgroup 8-

10A

Tomato 0.2 0.2 0.2 Tomato subgroup 8-10A

Vegetable, fruiting, subgroup 8-

10B

Vegetable, 

fruiting, group 8, 

except tomato 2.0

2.0 3.0 Pepper/eggplant subgoup 8-

10B

Tolerance increase to 

harmonize with Codex.

Fruit, citrus, group 10-10 Fruit, citrus, 

group 10 

10.0

10.0 15.0 Tolerance increase to 

harmonize with Codex.

Caneberry subgroup 13-07A Caneberry 

subgroup 13A

5.0

5.0 5.0

Bushberry subgroup 13-07B Bushberry 

subgroup 13B, 

Juneberry, 

Lingonberry, and 

Salal at 3.0 

3.0 5.0 Tolerance increase to 

harmonize with Codex.

Small fruit vine climbing, except 

fuzzy kiwifruit subgroup 13-07F

Grape 1.0 1.0 2.0 Fruit, small vine climbing, 

except fuzzy kiwifruit, 

subgroup 13-07F

Tolerance increase to 

harmonize with Codex.

Low growing berry subgroup 13-

07G, except cranberry

Strawberry 10.0 10.0 10.0 Berry, low growing, subgroup 

13-07G, except cranberry

Rapeseed subgroup 20A Canola, seed 1.0 1.0 1.0

Sunflower subgroup 20B Safflower, seed 

and sunflower, 

seed 0.5

0.5 0.5

Cottonseed subgroup 20C Cotton, 

undelinted seed 

0.6

0.6 0.7 Tolerance increase to 

harmonize with Codex.

Wasabi Herb subgroup 

19A, fresh leaves 

50

50 50 Wasabi, fresh

Wasabi, dry Herb subgroup

19A, dried leaves 

260

Not proposed 260 Wasabi, dry

Dragon-fruit Mango 2.0 2.0 2.0

Vegetable, tuberous and corm, 

subgroup 1C

0.03 6.0 8.0

Note to PM: In conjunction with establishment of the above tolerances, the existing tolerances 

for potato; onion, bulb; onion, green; vegetable, fruiting, group 8, except tomato; okra; tomato; 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 9 of 52

fruit, citrus, group 10; caneberry subgroup 13A; bushberry subgroup 13B; grape; strawberry; 

juneberry; lingonberry; salal; cotton, undelinted seed; canola, seed; sunflower, seed; crambe, 

seed; flax, seed; rapeseed, seed; rapeseed, Indian; mustard, field, seed; mustard, Indian, seed; 

mustard, seed; and safflower, seed need to be removed from 40 CFR §180.507(a).

Note to PM: The e-CFR includes the Z-isomer in the tolerance expression for livestock. The Zisomer should be removed from the tolerance expression for livestock.

Note to PM: The existing separate tolerance on potato should be removed and the established 

vegetable, tuberous and corm, subgroup 1C needs to be revised. 

2.2.4 Revisions to Petitioned-For Tolerances

HED recommends increasing the proposed US crop group tolerances for bushberry, subgroup 

13-07B, cottonseed, citrus fruit, 10-10, fruit vine climbing 13-07F [grape], and pepper/eggplant 

8-10B to harmonize with Codex. Based on the OECD calculation procedures for the current 

post-harvest potato data, HED recommends increasing the US tolerances for vegetable tuberous 

and corm, subgroup 1C to 8 ppm. See Table 2.2.3 for required revisions to the petitioned 

tolerances. 

2.3 Petition Recommendations 

860.1550 Proposed Tolerances

A revised Section B must be submitted to reflect the use on the entire vegetable, tuberous 

and corm, subgroup 1C, instead of post-harvest potatoes only. 

A revised Section F must be submitted to propose a tolerance for wasabi, dry at 260 ppm. 

2.4 Label Recommendations

2.4.1 Recommendations from Residue Reviews

A revised label must be submitted to reflect the use on the entire vegetable, tuberous and 

corm, subgroup 1C, instead of post-harvest potatoes only. 

2.4.2 Recommendations from Occupational Assessment 

Based on email correspondence with Syngenta (dated 11/04/2011), 0.6 gallons of Abound®(EPA 

Reg. No. 100-1098) should be mixed with 0.5 gallons of water and applied to 2,000 lbs of 

tuberous vegetables in the packing facility. These specific mixing and use instructions should 

be provided on the Abound®label for the post-harvest use. 

3.0 Introduction

Azoxystrobin is a broad spectrum fungicide for control of 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 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 10 of 52

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

Azoxystrobin acts by inhibiting electron transport. 

The proposed uses of azoxystrobin are for use on post-harvest tuberous and corm vegetables 

(subgroup 1C), and as field applications to dragon fruit and wasabi. IR-4 has also requested that 

the use profile of azoxystrobin be updated to incorporate the recent 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. 

Azoxystrobin is currently registered for use on a variety of field, vegetable, fruit, and nut crops 

as well as on ornamental plants and turf. 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), Graduate A+ (20.6% ai), Quadris Top 

(18.2% ai), Quilt® (7.0% ai) and Quilt XcelTM (13.5% ai). 

Azoxystrobin is proposed for use as a foliar application on wasabi using ground and chemigation 

equipment. Proposed application rates on wasabi range from 6.2-15.4 fl oz (0.10-0.25 lb ai)/A, 

with a maximum seasonal application rate of 1.5 lb ai/A. Applications should be made on a 7 

day schedule, with no more than 2 sequential applications before alternation with another type of 

fungicide. Wasabi is typically grown in greenhouses in the United States. 

Azoxystrobin is also proposed for use as a foliar application to dragon fruit using ground, aerial 

and chemigation equipment. Proposed application rates range from 6.2-15.5 fl oz or from 0.40-

0.8 fl oz/1,000 row feet (0.10-0.32 lb ai/A) on dragon fruit. Applications should be made on a 

10-14 day schedule, with no more than 2 sequential applications before alternation with another 

type of fungicide. 

Azoxystrobin is also proposed for use on post-harvest tuberous and corm vegetables (subgroup 

1C) using T-jet, controlled droplet application (CDA) or similar application methods. 

Applications to post-harvest tuberous and corm vegetables (subgroup 1C) may be made by 

mixing 0.6 fl oz Abound® with 0.5 gallons water and applying to one ton of tubers (2,000 lbs). 

3.1 Chemical Identity

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

Table 3.1. Azoxystrobin Nomenclature.

Compound

N N

O O

CN OCH3

O

H3CO
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 11 of 52

Table 3.1. Azoxystrobin Nomenclature.

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

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

benzeneacetate

CAS registry number 131860-33-8

End-use products (EP) Abound® Flowable Fungicide (EPA Reg. No. 100-1098);

Quilt® (EPA Reg. No. 100-1178); Graduate A+TM (EPA Reg. No. 100-1308);

Quadris TopTM (EPA Reg. No. 100-1313); and Quilt XcelTM (EPA Reg. No. 100-

1324)

Regulated metabolite, Z-isomer

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 Pow) of 2.5, a molecular weight of 

403 g/mol, and is considered relatively insoluble in water. For these reasons, the potential for 

azoxystrobin to cross biological barriers of the skin is somewhat limited. 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. Although azoxystrobin represents a borderline case of fat solubility, HED considers 

azoxystrobin residues fat-soluble. The physicochemical properties of azoxystrobin are 

summarized in Appendix B. 

3.3 Pesticide Use Pattern

In Section B of the petition, IR-4 submitted amended labels for Abound® Flowable Fungicide 

(EPA Reg. No. 100-1098), to add new uses on tuberous and corm vegetables (subgroup 1C)

(post-harvest), dragon fruit, wasabi, and crop group expansions. The petitioner has also 

requested amendment of the labels for Quilt® (EPA Reg. No. 100-1178), Graduate A+TM (EPA 

Reg. No. 100-1308), Quadris TopTM (EPA Reg. No. 100-1313), and Quilt XcelTM (EPA Reg. No. 

100-1324) to reflect the revision/expansion of the crop groups. Table 3.3.1 provides a summary 

of the proposed use sites of azoxystrobin. Table 3.3.2 provides a summary of the use pattern for 

the crop group conversions.

N N

O O

CN

O OCH3

H3CO
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 12 of 52

Table 3.3.1. Proposed Uses of Azoxystrobin

Product

(EPA 

Registration No.)

Use Site Application 

Method

Application 

Rate Range 

(lb ai/A)

Maximum 

Seasonal 

Application 

Rate (lb 

ai/A)

Comments

Abound® (100-

1098) 22.90% 2.08 

lbs ai/gal

Wasabi Ground and 

Chemigation 0.10-0.25 1.49

Application should be made on a 7 day schedule, no more 

than 2 sequential applications before alternation with 

another type of fungicide, 0 day PHI

Dragon Fruit 

Ground, 

Aerial, 

Chemigation

0.10-0.32 

(soil borne 

disease)

1.49

10-14 day application schedule, no more than 2 sequential 

applications before alternation with another type of 

fungicide, 0 day PHI

Post-Harvest 

Potatoes

T-jet, CDA or 

similar

0.6 fl oz/ton 

of tubers

Do not make more than one post-harvest application. In 

response to the question concerning post harvest use on 

potatoes for azoxystrobin, the potatoes will not be treated in 

the field - only at the potato storage facility as they are 

being placed into storage. The treatment is a non-recovery 

spray with no waste or run-off.

Table 3.3.2 Azoxystrobin Use Pattern for Crop Group Conversions

Product 

(EPA 

Registration 

No.)

Use Site Application 

Method

Application Rate 

Range (lb ai/A)

Maximum 

Seasonal 

Application 

Rate (lb 

ai/A)

Comments

Abound®

(100-1098)

22.9%

2.08 lbs ai/gal

Onion, Subgroups 13-07 A 

& B

Ground, 

Aerial, 

Chemigation

0.10-0.32 (soil borne 

disease) 1.49

Do not apply more than one application 

before alternation with another type of 

fungicide.

Vegetable, Fruiting, 

Subgroup 8-10 A

Ground, 

Aerial, 

Chemigation

0.08-0.10 0. 6

Applications should be made on a 5-7 

schedule for late blight, 7-21 day schedule 

for other diseases, with no more than 2 

sequential applications before alternation 

with another fungicide not in group 11. 

0 day PHI

Vegetable, Fruiting,

Subgroup 8-10B

Ground, 

Aerial, 

Chemigation

0.10-0.32 (soil borne 

disease) 1

Applications should be made on a 7-14 

day schedule.

0 day PHI 

Do not apply more than 2 sequential 

applications before alternation with 

another fungicide not in group 11.

Bushberry Subgroup 13-07 

B

Ground, 

Aerial, 

Chemigation

0.10-0.25 0.74

Applications should be made on a 7-14 

day schedule, with no more than 2 

sequential applications before alternation 

with another fungicide not in group 11. 

0 day PHI

Caneberry Subgroup 13-

07A

Ground, 

Aerial, 

Chemigation

0.10-0.25 1.49

Applications should be made on a 7-14 

day schedule, with no more than 2 

sequential applications before alternation 

with another fungicide not in group 11. 

0 day PHI

Small Fruit Vine 

Climbing, except fuzzy 

kiwi fruit Subgroup 13-

07F

Ground, 

Aerial, 

Chemigation

0.16-0.25 1.49

Applications should be made on a 10-14 

day schedule, with no more than 2 

sequential applications before alternation 

with another fungicide not in group 11. 

14 day PHI.
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 13 of 52

Table 3.3.2 Azoxystrobin Use Pattern for Crop Group Conversions

Product 

(EPA 

Registration 

No.)

Use Site Application 

Method

Application Rate 

Range (lb ai/A)

Maximum 

Seasonal 

Application 

Rate (lb 

ai/A)

Comments

Low Growing Berry 

Subgroup 13-07G (except 

cranberry)

Ground, 

Aerial, 

Chemigation

0.10-0.32 (soil borne 

disease) 1

Applications should be made on a 7-10 

day schedule, with no more than 2 

sequential applications before alternation 

with another fungicide not in group 11. 

For dip applications at transplanting, mix 

up to 8 fl oz product per 100 gals water,

dip plants for 2-5 minutes, and plant 

treated plants as quickly as possible.

0 day PHI

Oilseeds Subgroups A, B, 

C

Ground, 

Aerial, 

Chemigation

0.10-0.25 0.44

Do not apply more than one application 

before alternation with another type of 

fungicide.

30 day PHI

Fruit, Citrus Group 10-10

Ground, 

Aerial, 

Chemigation

0.20-0.32 (soil borne 

disease) 1.49

Applications should be made on a 7-21 

day schedule, with no more than 2 

sequential applications before alternation 

with another fungicide not in group 11. 

0 day PHI

Graduate A+TM 

(100-1308)

20.6%

1.99 lb ai/gal

Post Harvest Citrus

32-64 fl oz/100 gal (inline dip/drench) or 32-64 

fl oz/250,000 lb of fruit 

(in line aqueous or fruit 

coating spray 

application)

Do not make more than 2 applications to 

citrus fruit.

Quadris TopTM

(100-1313)

18.2%

1.67 lb ai/gal

Fruit, Citrus Group 10-10 Ground or 

Aerial 0.13-0.2

Quilt®

(100-1178)

7.0%

0.62 lb ai/gal

Bushberry Subgroup 13-07 

B

Ground or 

Aerial 0.07-0.10 0.96

Applications should be made on a 7-10 

day schedule, with no more than 2 

consecutive applications for mummy 

berry; other diseases require a 14 day

application interval.

Make no more than 2 consecutive 

applications, and no more than 3 

applications per crop.

30 day PHI

Caneberry Subgroup 13-

07A

Ground or 

Aerial 0.07-0.10 0.96

Applications should be made on a 7-14 

day schedule with no more than 2 

sequential applications before alternation 

with another type of fungicide.

30 day PHI

Onion, Subgroups 13-07 A 

& B

Ground or 

Aerial 0.07-0.13 0.51

Applications should be made on a 7-10 

day schedule with no more than 2 

sequential applications before alternation 

with another type of fungicide.

14 day PHI for dry bulb, 0 day PHI for 

green onion types.
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 14 of 52

Table 3.3.2 Azoxystrobin Use Pattern for Crop Group Conversions

Product 

(EPA 

Registration 

No.)

Use Site Application 

Method

Application Rate 

Range (lb ai/A)

Maximum 

Seasonal 

Application 

Rate (lb 

ai/A)

Comments

Quilt XcelTM 

(100-1324)

13.5%

1.18 lb ai/gal

Berries Bushberry 

Subgroup 13-07B

Ground or 

Aerial 0.13-0.19 0.76

For mummyberry, apply first at the green 

tip stage and repeat every 7-10 days and 

do not apply more than 2 consecutive 

applications. 

For other diseases, applications should be 

made on a 7-14 day schedule with no 

more than 2 consecutive applications.

Make no more than 3 applications of 

Quilt XL (or other group 11 fungicides) 

per crop 

30 day PHI

Berries Caneberry 

Subgroup 13-07A

Ground or 

Aerial 0.13-0.19 0.98

Applications should be made on a 14 day 

schedule with no more than 2 consecutive 

sprays.

Make no more than 3 applications of 

QuiltXcel or other group 11 fungicide.

30 day PHI

Onion, Subgroups 13-07 A 

& B

Ground or 

Aerial

0.13-0.19 (purple blotch, 

rust, cladoporium leaf 

blotch), 0.16-0.24 (white 

rot, downy mildew, leaf 

blight)

0.52

Applications should be made on a 7-10 

day schedule 

Apply only once before alternating to 

another group 11 fungicide

14 day PHI for bulb onions, 0 day PHI 

green onions

Low Growing Berry 

Subgroup 13-07G (except 

cranberry)

Ground or 

Aerial 0.13 0.52

Applications should be made on a 10-14 

day schedule with no more than 2 

consecutive applications.

Make no more than 4 applications of 

Quilt or similar fungicide.

0 day PHI

3.4 Anticipated Exposure Pathways

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

proposed new uses of azoxystrobin on tuberous and corm vegetables, subgroup 1C, wasabi and 

dragon fruit, and the revisions to various crop groups. 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. 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 15 of 52

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. 

Extensive data on food consumption patterns are compiled by the USDA under the Continuing 

Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all 

registered food uses of a pesticide. These data are analyzed and categorized by subgroups based 

on age, season of the year, ethnic group and region of the country. Additionally, OPP is able to 

assess dietary exposure to smaller, specialized subgroups and exposure assessments are 

performed when conditions or circumstances warrant. Whenever appropriate, non-dietary 

exposures based on home use of pesticide products and associated risks for adult applicators and 

for children 3 to < 6 years old, youths and adults entering or playing on treated areas postapplication are evaluated. Further considerations are currently in development as OPP has 

committed resources and expertise to the development of specialized 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

4.1 Toxicology Studies Available for Analysis

The toxicology data for azoxystrobin are sufficient and are of good quality for selecting toxicity 

endpoints and points of departure for risk assessment. The available toxicology studies include 

(1) subchronic oral toxicity studies in rats and dogs; (2) a 21 day dermal toxicity study in rats; (3) 

developmental toxicity studies in rats and rabbits; (4) a 2-generation reproduction study in rats; 

(5) a chronic toxicity study in dogs; (6) a carcinogenicity study in mice and a combined chronic 

toxicity/carcinogenicity study in rats; (7) a battery of the required genotoxicity studies; (8) a 

metabolism study in rats; (9) acute and subchronic neurotoxicity studies; and (10) a dermal 

penetration study in rats. 

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)

Pharmacokinetics and metabolism studies in rats showed that azoxystrobin was absorbed and 

distributed broadly following oral administration. Based upon the results of the various 

experiments, absorption of azoxystrobin was difficult to accurately assess. For the single high-dose 

group, assessment of biliary excretion suggested approximately 70% absorption with approximately 

32% of administered radioactivity remaining as parent compound in the gastrointestinal tract. The 

greatest amounts of absorbed azoxystrobin were distributed to organs associated with either 

metabolism or excretory function, especially the liver and kidneys. Less than 0.5% of the 

administered dose was detected in the tissues examined on the 7th day after dosing which 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 16 of 52

suggests minimal potential for bioaccumulation. There were no apparent sex-related differences 

in distribution. The absorbed azoxystrobin appeared to be extensively metabolized. A metabolic 

pathway, consistent with the data on metabolite identification and quantitation, was proposed 

showing hydrolysis and subsequent glucuronide conjugation as the major biotransformation 

process. A total of 15 metabolites were detected in the excreta and subsequently identified. 

Seven additional metabolites were detected but not identified. None of the unidentified 

metabolites represented more than 4.9% of the administered dose. The glucuronide conjugate 

(metabolite V) was the most prevalent biliary metabolite in both males and females. The parent 

compound was not detected in the bile, with the exception of metabolite V, (which represented 

29.3% (males) and 27.4% (females) of the administered dose); the other biliary metabolites 

represented less than 10% of the administered dose. Minor qualitiative and quantitative 

differences in biliary metabolites were observed in males and females. The primary route of 

elimination was via the feces ( 73-89% of the administered dose) followed by the urine ( 9-

18%). The fecal vs. urinary route of excretion did not vary considerably with dose. There were 

no apparent sex- or dose-related differences in the pattern of excretion. 

4.2.1 Dermal Absorption

No adverse effects were seen up to the limit dose (1,000 mg/kg/day) in a 21-day dermal repeated 

dose study in rats. In an acceptable dermal absorption study with 24 male rats, percutaneous 

absorption was minimal (< 4.2%) and did not appear to exhibit a dose-response relationship. 

Time-course data indicated that most absorption occurred during the first 0.5 hours and that this 

represented approximately 0.9% of the administered dose. Limited absorption precluded accurate 

assessment of distribution and metabolite characterization. Both fecal and urinary excretion 

were quantified, the former representing about 6% or less of total absorption and the latter 

accounting for <0.1% of the absorbed dose over a 24-hr period. Overall recovery of 

administered radioactivity was 95-105%.

4.3 Toxicological Effects

With repeated dosing by the oral route, the liver and bile ducts were consistently the target 

organs of azoxystrobin toxicity. Liver and biliary effects were seen in rats (increased liver 

weights, gross and histopathological lesions of the bile duct and liver), and in dogs (increased 

liver weights, clinical observations (including fluid feces and salivation) and clinical chemistry 

alterations (including increased levels of alkaline phosphatase, serum, and serum gammaglutamyl transferase; and decreases in albumin). These effects seen are indicative of changes to

liver/biliary function. Decreased body weight (rats and mice) and decreased body weight gain 

(rats and rabbits) were also consistent findings across studies and species. Other effects 

including decreased food intake/utilization, increased diarrhea and other clinical toxicity 

observations such as urinary incontinence, salivation, hunched postures and distended abdomens 

were also seen in various studies (developmental toxicity, reproduction, and 90 day oral toxicity) 

in rats. All these effects do not suggest immunotoxic or neurotoxic potential for azoxystrobin. 

No developmental effects were seen in the rabbit and rat developmental toxicity studies and no 

reproductive or offspring effects were seen in the 2-generation rat reproduction study. In the 

reproduction study, decreased body weights and increased adjusted liver weights were observed 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 17 of 52

at the same dose in both offspring and parental animals. Therefore, the toxicity data showed no 

increased susceptibility in the young. 

In the acute and subchronic neurotoxicity studies, there were no consistent indications of 

treatment-related neurotoxicity. There was no evidence of neurotoxicity seen in the acute 

neurotoxicity study in rats from a single gavage dose up to 2,000 mg/kg. There was also no 

evidence of neurotoxicity seen in the subchronic neurotoxicity study in rats up to the highest 

dose tested (201 mg/kg/day). Based on the toxicity profile of azoxystrobin, a developmental 

neurotoxicity study in rats is not required (B. Tarplee and J. Rowland, HED Doc. No. 012844, 

09/03/1998). 

Although azoxystrobin induced a weak mutagenic response in the mouse lymphoma assay (non 

linear, slight but significant increases in the mutation frequency of mouse lymphoma cells), the 

activity expressed in vitro is not expected to be expressed in whole animals, for the following 

reasons: (1) although colony sizing was not performed in the mouse lymphoma assay, it is likely 

that the increased mutation frequencies seen in this study were associated with a chromosomal 

rather than point mutational event. This interpretation is based on the similarity of the response 

uncovered in the mouse lymphoma assay to the clastogenic response seen with and without S9 

activation in human lymphocytes; and (2) the negative findings of the UDS assay, the lack of an 

oncogenic effect in rat or mouse long-term feeding studies and the absence of significant 

reproductive or developmental toxicity attributable to a mutagenic mode of action (i.e. decreased 

total implants, increased resorptions). Hence, it can be concluded that azoxystrobin is active in 

vitro but this genotoxicity is not expressed in whole animals (G. Dannan, HIARC, 09/25/2000). 

There was no evidence of carcinogenicity in rats and mice at acceptable dose levels; 

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. 

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

The HED azoxystrobin risk assessment team evaluated the quality of the toxicity and exposure 

data and recommends that the FQPA SF be retained at 3X to account for using a LOAEL to 

extrapolate to a NOAEL for the acute dietary exposure POD. The FQPA SF should be retained, 

despite the data showing no increased susceptibility in rats and rabbits exposed in utero and/or 

postnatally to azoxystrobin. HED selected the acute neurotoxicity study in rats, where diarrhea 

was seen two hours post dosing at all dose levels (up to and including the LOAEL) to represent 

the acute dietary exposure scenario. HED is confident that a SF of 3X (as opposed to 10X) is 

adequately protective due to (1) the relatively insignificant nature of the effect (transient diarrhea 

seen in the rat), (2) the fact that diarrhea was only seen in studies involving gavage dosing in the 

rat but not in repeat dosing through dietary administration in rats, mice, rabbits and dogs, (3) the 

very high dose level needed to reach the acute oral lethal dose (LD)50 (>5,000 mg/kg), and (4) 

the overall low toxicity of azoxystrobin. NOAELs were used for short-term, intermediate-term, 

and chronic risk assessments. The FQPA SF was reduced to 1X for all exposure scenarios other 

than acute dietary because azoxystrobin showed no evidence of increased susceptibility in the 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 18 of 52

young. Although an immunotoxicity study is needed to complete the database, the selected 

toxicity endpoints and points of departure for risk assessment are based on the most sensitive and 

relevant data. Currently, there are no concerns for structural immunotoxicity based on the results 

of existing studies. 

4.4.1 Completeness of the Toxicology Database

The toxicity database for azoxystrobin is considered adequate for selecting toxicity endpoints 

and points of departure for risk assessment, with the exception of an immunotoxicity study. 

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. Therefore, EPA does not believe that 

conducting an 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. 

4.4.2 Evidence of Neurotoxicity

Clinical signs noted in the acute and subchronic neurotoxicity studies were not considered 

treatment related because of lack of dose-response, inconsistency of observations at different 

time points and/or small magnitude of response. There is no need for a developmental 

neurotoxicity study or additional uncertainty factors (UFs) to account for neurotoxicity. 

4.4.3 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. 

4.4.4 Residual Uncertainty in the 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 

assumed 100% of the proposed and registered crops were treated, and utilized tolerance level 

residues for all existing and proposed commodities, except citrus fruits where the highest field 

trial residue was used. The chronic dietary exposure assessment used tolerance level residues for 

all commodities and % crop treated (%CT) estimates when available (Screening Level Usage 

Analysis (SLUA), 07/13/11). 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. 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 19 of 52

In addition, the previous residential exposure assessment incorporates similarly conservative 

assumptions in the assessment of post-application exposure of children and in the incidental oral 

exposure assessment for children. These assessments will not underestimate the exposures and 

risks posed by azoxystrobin. 

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose-Response Assessment

The toxicity endpoints and points of departure are presented in Table 4.5.4.

For azoxystrobin, HED has selected the most sensitive and protective endpoints from the 

available database to establish points of departure for the risk assessment. For acute oral 

exposure, an acute neurotoxicity study in rats was used to select the dose and endpoint for 

establishing the aRfD (0.67 mg/kg/day) for the general population. The LOAEL of 200 mg/kg is 

based on diarrhea seen at two hours post-dosing at all dose levels up to and including the 

LOAEL. For chronic oral exposure, a combined chronic toxicity/carcinogenicity study in rats 

was used to select the dose and endpoint for establishing the cRfD (0.18 mg/kg/day) for the 

general population. The LOAELs (82.4/117 mg/kg/day for males and females, respectively) are 

based on reduced body weights in both sexes and bile duct lesions in males. A prenatal 

developmental oral toxicity study in rats (NOAEL=25 mg/kg/day) was used to assess short-term 

incidental oral and short-term inhalation exposure based on increased maternal diarrhea, urinary 

incontinence, and salivation seen at the LOAEL (100 mg/kg/day). A 90-day feeding study in 

rats (NOAEL=20 mg/kg/day) was used to assess intermediate-term incidental oral and inhalation 

exposure based on decreased body weight gains in both sexes, and clinical signs indicative of 

reduced nutrition seen at the LOAEL (211/223 mg/kg/day in males/females). No dermal or 

systemic toxicity was seen at the limit dose (1,000 mg/kg/day) in a 21-day repeated dose dermal 

study in rats. Therefore, short- and intermediate-term dermal risk of azoxystrobin was not 

assessed. Since no inhalation absorption data are available, toxicity by the inhalation route is 

considered to be equivalent to the estimated toxicity by the oral route of exposure (i.e. there is no 

inhalation absorption factor). 

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

No dermal hazard was identified and dermal exposure to azoxystrobin was not assessed. 

Therefore, dermal and inhalation routes of exposure are not combined. 

4.5.3 Cancer Classification and Increased Tumor Incidence Risk Assessment 

Recommendation

Azoxystrobin is classified as ―Not likely to be Carcinogenic to Humans.‖ Cancer risk 

assessments do not need to be conducted. 

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 20 of 52

Table 4.5.4. 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 

up to and including to 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.

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.

Based on the available toxicity 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 oral 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 21 of 52

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 

References: 

- Azoxystrobin: Acute and Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk 

Assessments for Section 3 Petition For Use On Tuberous and Corm Vegetables Subgroup 1C (Postharvest); Dragon Fruit; Wasabi; and Crop Group/Subgroup Expansions for Bulb Vegetables 3-07A and 3-

07B; Caneberries 13-07A; Bushberries 13-07B; Small Fruit Vine Climbing 13-07F, Except Fuzzy 

Kiwifruit; Low growing Berry 13-07G, Except Cranberry; Low Growing Berry 13-07H, Except 

Strawberry; Citrus Crop Group 10-10; Fruiting Vegetable Crop Group 8-10; and Oilseed Crop Group 20,

M. Negussie, DP#390838, 11/29/11. 

- Drinking Water Exposure Assessment for New Uses of Azoxystrobin on Wasabi, Dragon-fruit and 

Sugarcane, and the Proposed Tolerances for Residues of Azoxystrobin for Use on Onion subgroups, 

Fruiting Vegetables Subgroups, Small Fruit & Berry Subgroups, Oilseed Subgroups; and the Proposed 

Increased Tolerance for Tuberous & Corm Vegetables Subgroup, R. Baris, DP#389703/394475, 11/28/11.

- Azoxystrobin. Section 3 Petition For Use On Potatoes (Post-harvest); Dragon Fruit; Wasabi; and Crop 

Group Expansions for Bulb Vegetables 3-07A and 3-07B; Caneberries 13-07A; Bushberries 13-07B; Small 

Fruit Vine Climbing 13-07F, Except Fuzzy Kiwifruit; Low growing Berry 13-07G, Except Cranberry; Low 

Growing Berry 13-07H, Except Strawberry; Citrus Crop Group 10-10; Fruiting Vegetable Crop Group 8-

10; and Oilseed Crop Group 20. Summary of Analytical Chemistry and Residue Data, M. Negussie, 

DP#390152, 11/16/11. 

- Drinking Water Assessment for amended label Quadris TopTM fungicide (EPA Reg. No. 100-1313) 

Azoxystrobin for use on golf course turf (only), J. Wolf, DP#371383, 01/16/10. 

5.1 Metabolite/Degradate Residue Profile

5.1.1. Summary of Plant and Animal Metabolism Studies

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

the IR-4 petition. Metabolism studies in grapes, peanuts, and wheat were submitted in 

conjunction with earlier azoxystrobin petitions, PP#s 5F4541 and 6F4762. The database is 

adequate for determining azoxystrobin residues of concern. A listing of the azoxystrobin 

metabolites is provided in Appendix D.

Primary Crops

Azoxystrobin is systemic. Azoxystrobin undergoes photochemical isomerization to produce the 

Z-isomer and is extensively metabolized in plants. The parent compound undergoes cleavage of 

the ether linkages between the phenylacrylate and pyrimidinyl rings and the cyanophenyl and 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 22 of 52

pyrimidinyl rings, with subsequent oxidation, hydrolysis, and/or reduction of the primary 

metabolites to form numerous secondary metabolites. HED has determined that the residues of 

concern in/on plants for tolerance expression and risk assessment purposes are azoxystrobin and 

its Z-isomer.

Rotational Crops

Adequate confined rotational crop metabolism studies have previously been presented in 

PP#6F4762 and re-evaluated in PP#9F6058. Total radioactive residues (TRR), expressed as 

[

14C]azoxystrobin equivalents, accumulated at >0.01 ppm in the raw agricultural commodities of 

lettuce, radishes, and wheat planted in sandy loam soil 30, 200, and 365 days after treatment of 

the soil with [14C]azoxystrobin at 1.8 lb ai/A. Residues were highest in rotated crop 

commodities from the 30-day plantback intervals (PBIs) and declined at subsequent PBIs. 

Azoxystrobin is more extensively metabolized in rotational crops than in primary crops. The 

residues of concern in rotational crops are parent and the Z-isomer.

Livestock 

The nature of the residue in livestock is adequately understood based on acceptable metabolism 

studies conducted on goats and laying hens. HED has determined that the residue of concern in 

livestock is parent azoxystrobin only. 

In the goat metabolism study, azoxystrobin and compounds 2, 20, 23, and 28 were identified in

kidney, and azoxystrobin and compounds 2, 3, 10, 13, 20, and 28 were identified in liver.

Although azoxystrobin is highly metabolized in livestock kidney and liver, these organs are 

minor components of the human diet and all residues were present at low levels/low percentages 

of the total radioactive residue. 

In poultry, azoxystrobin and compound 28 were identified in egg yolk and compound 28 was 

identified in liver. Residues in extracts of egg whites, muscle, skin with underlying fat, or 

peritoneal fat were <0.01 

ppm. 

5.1.2 Summary of Environmental Degradation

Azoxystrobin is relatively persistent, but not highly mobile. Azoxystrobin is stable to hydrolysis 

at pH 5, 7, and 9 at 25 C. Azoxystrobin degrades through photolysis in water and soil and to a 

lesser extent by microbial-mediated degradation. The dissipation half-life (T1⁄2) of azoxystrobin 

by photolysis on soil ranges between 17.6 to 28.4 days (DT50=11 days). The dissipation of 

azoxystrobin by photodegradation half-life in surface water ranges between 11.1 to 17 days.

Azoxystrobin will slowly biotransform in aerobic and anaerobic soils. The aerobic soil 

metabolism half-lives range from 72 to 164 days. Three major degradates were detected. HED 

has previously determined that the only residue of concern for dietary exposure is parent 

azoxystrobin. Thus, only the parent was considered in the drinking water assessment.

The soil/water partitioning coefficients (Freundlich Kf) for azoxystrobin range from 1.5 to 23 

mL/g in seven soils. Kocs range from 210 to 1690 mL/goc. Azoxystrobin exhibits a low to 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 23 of 52

moderate mobility in all soils tested in the mobility studies. The relatively low mobility was 

confirmed in the field studies where azoxystrobin dissipated slowly on the surface (0-6 inch) of 

non-flooded soils. No azoxystrobin residue was found in soil layers deeper than 6 inches. The 

data suggest that azoxystrobin may be transported to surface and ground waters under some use 

conditions.

Based on environmental fate data, the dissipation of azoxystrobin appears to be predominately 

dependent on photodegradation and to a lesser extent on microbial-mediated degradation, and 

possible transport to surface and ground waters. Azoxystrobin is expected to have a high to 

moderate mobility in runoff and low to moderate potential to leach. The data suggest that 

azoxystrobin may be transported to surface and ground waters under some use conditions.

Since photodegradation is a major route of degradation for azoxystrobin, the dissipation of 

azoxystrobin is expected to be dependent on conditions of the water (e.g. sediment loading, 

depth, etc.) affecting sunlight penetration. For example, azoxystrobin should not persist in clear 

shallow water bodies, but will be more persistent in turbid and/or deeper waters, particularly 

those with long hydrological residence times.

5.1.3 Comparison of Metabolic Pathways

Azoxystrobin is metabolized in rats by undergoing hydrolysis and is biotransformed during a 

subsequent glucuronide conjugation process. Fifteen metabolites were detected in the excreta of 

rats studied, and seven additional metabolites were detected but not identified. None of the 

unidentified metabolites represented more than 4.9% of the administered dose. The glucuronide 

conjugate (metabolite V) was the most prevalent biliary metabolite in both males and females. 

Azoxystrobin undergoes photochemical isomerization to produce the Z-isomer and is extensively 

metabolized in plants. The parent compound undergoes cleavage of the ether linkages between 

the phenylacrylate and pyrimidinyl rings and the cyanophenyl and pyrimidinyl rings, with 

subsequent oxidation, hydrolysis, and/or reduction of the primary metabolites to form numerous 

secondary metabolites. HED has determined that the residues of concern in/on plants for 

tolerance expression and risk assessment purposes are azoxystrobin and its Z-isomer.

The metabolic pathway in plants and animals is qualitatively similar, although the Z- isomer was 

not identified in animals; the major biotransformation process is hydrolysis.

5.1.4 Residues of Concern Summary 

Table 5.1.4. 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
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 24 of 52

Table 5.1.4. 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

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/expansions of crop groups/subgroups of the fungicide azoxystrobin in/on dragon fruit; 

wasabi; tuberous and corm vegetables subgroup 1C; onion, bulb and green subgroups 3-07A and 

B; caneberry subgroup 13-07A; bushberry subgroup 13-07B; small fruit vine climbing 13-07F, 

except fuzzy kiwifruit; low growing berry 13-07G, except cranberry; fruit, citrus group 10-10; 

fruiting vegetable group 8-10A and B; and oilseed crop group 20.

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, and wheat bran. 

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.

Residue chemistry studies are supported by adequate 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. 

Proposed Uses 

Other than the post-harvest potato field trial data (MRID 48437101), no new residue field trial 

data were submitted to support the proposed tolerances. The changes are a result of revised crop 

groups and are conversions from existing groups/subgroups or representative commodities, and 

have been adequately assessed previously. The proposed tolerances for the dragon fruit and 

wasabi are extrapolated from existing azoxystrobin tolerances on mango (2.0 ppm) and herb 

subgroup 19A, fresh (50 ppm), respectively. 

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

Commodity Analyte Total App. 

Rate 

DAA Residue Levels (ppm)1
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 25 of 52

g a.i./

2000 lb

lb a.i./

2000 lb

[g 

a.i./100 

kg 

n Sample 

Min.

Sample 

Max.

LAFT3 HAFT3 Median Mean Std. Dev.4

TRT 02 (Conveyor Belt or Roller Table)

Potato tubers Azoxystrobin 4.0473-

4.5105

0.0089-

0.0099

[0.45-

0.50]

0 10 0.992 4.15 0.994 3.79 2.22 2.40 1.20

R230310 10 <0.01 <0.01 0.01 0.01 0.01 0.01 N/A

Total Residues 10 <1.002 <4.16 1.004 3.80 2.23 2.41 1.20

TRT 03 (Surface)/Stationary

Potato tubers Azoxystrobin 4.0997 0.0090

[0.45]

0 2 1.05 1.22 1.14 1.14 N/A N/A N/A

R230310 2 <0.01 <0.01 0.01 0.01 N/A N/A N/A

Total Residues 2 <1.06 <1.23 1.15 1.15 N/A N/A N/A

TRT 04 (Spray Chamber)

Potato tubers Azoxystrobin 4.0309 0.0089

[0.44]

0 2 3.50 3.57 3.54 3.54 N/A N/A N/A

R230310 2 <0.01 <0.01 0.01 0.01 N/A N/A N/A

Total Residues 2 <3.51 <3.58 3.55 3.55 N/A N/A N/A

TRT 05 (Brush Table)

Potato tubers Azoxystrobin 4.0850 0.0090

[0.45]

0 2 2.23 2.31 2.27 2.27 N/A N/A N/A

R230310 2 <0.01 <0.01 0.01 0.01 N/A N/A N/A

Total Residues 2 <2.24 <2.32 2.28 2.28 N/A N/A N/A

Combined Treatments

Potato tubers Azoxystrobin 4.0309-

4.5105

0.0089-

0.0099

[0.44-

0.50]

0 1610.992 4.15 -- -- 2.25 2.37 1.12

8

2

-- -- 0.994 3.79 2.25 2.37 1.15

R230310 161<0.01 <0.01 -- -- 0.01 0.01 N/A

8

2

-- -- 0.01 0.01 0.01 0.01 N/A

Total Residues 161<1.002 <4.16 -- -- 2.26 2.38 1.12

8

2

-- -- 1.004 3.80 2.25 2.37 1.15

1

n = no. of samples. For calculation of median, mean, and standard deviation, the LOQ (0.01 ppm) was used for any results

reported as <LOQ in Table C.3.

2

n = no. of field trials; statistical calculations are based on per-trial average values. 

3 LAFT = lowest-average-field-trial; HAFT = highest-average-field-trial.

4 N/A = Not applicable.

Syngenta submitted an acceptable processing study for azoxystrobin on potato following postharvest treatment. Processing of the tuber RAC with quantifiable residues of azoxystrobin did 

not result in the concentration of residues in potato fractions (processing factors were all <1x). 

Residues of R230310 were below the LOQ in/on all samples of potato RAC, flakes, chips, and 

wet peel. Therefore, processing factors were not calculated. The observed concentration factors 

were less than the theoretical concentration factors. Acceptable methods were used for the 

determination of residues of azoxystrobin and the Z-isomer metabolite. The sample storage 

conditions and durations for azoxystrobin analyses are supported by adequate storage stability 

data. Results are provided in Table 5.2b. 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 26 of 52

Table 5.2b. Residue Data from Potato Processing Studies with Azoxystrobin.

RAC Processed 

Commodity

Total Rate

DAA

Residues (ppm) Processing Factor1,2

g a.i./

2000 

lb

lb a.i./

2000 lb Azoxystrobin R230310 Total 

Residues Azoxystrobin R230310 Total Residues

Potato Tubers

(RAC)

4.1357 0.0091 0 0.938 <0.01 <0.948 -- -- --

Flakes <0.01 <0.01 <0.02 <0.01x NC <0.02x

Chips 0.0111 <0.01 <0.0211 0.01x NC <0.02x

Wet peel 0.846 <0.01 <0.856 0.90x NC <0.90x

1 NC = Not calculated; residues were below the LOQ (<0.01 ppm for all in analytes) in the RAC and processed fraction.

2

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

Livestock

The livestock feedstuffs associated with this petition are potato culls and processed potato waste; 

in addition, there are established tolerances for numerous livestock feedstuffs. The previously 

estimated livestock dietary burdens of azoxystrobin were revised to include the processed potato 

waste (dairy cattle only). 

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

goat, hog, horse, and sheep are adequate; no revision to the existing tolerances is 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)]. No tolerances are 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 amended uses 

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

the existing rotational crop restrictions are needed. The rotational crop restrictions on the label 

for EPA Reg. No. 100-1098 are adequate. 

5.3 Water Residue Profile

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

DP371383, 01/6/2010) were more conservative than the most recent drinking water assessment 

(R. Baris, DP389703/394475, 11/28/2011). 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 crop, 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/.
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 27 of 52

The proposed rates of application for wasabi and dragon fruit are lower than for turf. Therefore, 

the EDWCs reported for turf are representative of these current actions. EDWCs recommended 

for use in the human health risk assessment for all proposed/registered crops are listed in Table 

5.2. 

Table 5.2 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 assumed 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. 

For %CT estimates used in the dietary exposure assessment, see Appendix E. 

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 18% 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 

41.7% of the aPAD. The results are reported in Table 5.4.4. All population subgroups were 

below the level of concern. 

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 

= 9.202 ppm]), used 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 6.7% 

of the cPAD for the general U.S. population. The chronic dietary exposure for the highest 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 28 of 52

reported exposed population subgroup, children 1-2 years old, utilized 15.5% of the cPAD. The 

results are reported in table 5.4.4. All population subgroups were below the level of concern. 

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

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

information for some crops (Appendix E). 

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 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 0.120415 17.97 0.012050 6.7

N/A N/A

All Infants (< 1 year old) 0.146102 21.81 0.015196 8.4

Children 1-2 years old 0.279450 41.71 0.027847 15.5

Children 3-5 years old 0.218767 32.65 0.024065 13.4

Children 6-12 years old 0.144459 21.56 0.015268 8.5

Youth 13-19 years old 0.115468 17.23 0.011208 6.2

Adults 20-49 years old 0.100143 14.95 0.010190 5.7

Adults 50+ years old 0.094256 14.07 0.010004 5.6

Females 13-49 years old 0.102333 15.27 0.009822 5.5

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

References: 

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

Uses on Dragon Fruit, Wasabi, and Post-Harvest Potatoes, 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, 

DP390837, 12/01/2011.

- Azoxystrobin. Human Health Risk Assessment for a Section 3 New/Amended Uses on Non-grass Animal 

Feeds (Crop Group 18), Sorghum, Wheat, Cotton, and Wild Rice, S. Piper, DP344389, 04/30/2008.

Residential exposure and risks from use on turf and indoor surfaces were described in a previous 

separate document (S. Piper, D344389, 04/30/2008). The residential uses for azoxystrobin have 

not changed. 

6.1 Residential Handler Exposure
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 29 of 52

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

applicators to residential settings. However, azoxystrobin is currently registered for use 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, it is registered on indoor carpets/other surfaces by noncommercial applicators, and in treated paints (preservative incorporation). It is assumed that 

most residential use 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. Although PoDs from an oral study were used to assess residential 

handler inhalation risks for azoxystrobin, HED does not believe this assessment is underprotective of adult handlers. Because there was no dermal endpoint chosen for azoxystrobin, risk 

from exposure to azoxystrobin was assessed for the inhalation route only. 

HED’s level of concern 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. 

The worst case residential handler scenario is summarized in Table 6.1. The MOE was 1,400 for 

residential handlers painting with an airless sprayer, and is not of concern to HED (i.e. an MOE 

> 100). 

Table 6.1. Summary of Worst-Case Residential Handler Exposures and Risks.

Scenario

Activity Application 

Rate

Area 

Treated/Amount 

Applied (per day)

Inhalation 

UE (mg/lb 

ai)

Dose 

(mg/kg/day) MOE1

Residential Handler Painting with 

Airless Sprayer

1.0% ai by 

weight 150 lb 0.83 0.078 1,400

1. MOE - NOAEL/Dose where NOAEL is 25 mg ai/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. 

Because no dermal endpoint was chosen for azoxystrobin, and inhalation post-application 

exposures are considered negligible, post-application residential exposure scenarios are not 

combined. As a result, risk assessments have only been completed for post-application scenarios 

in which incidental oral exposures are expected. The MOEs for worst-case post-application 

incidental oral exposures are summarized in Tables 6.2a and 6.2b. The MOEs ranged from 480 

to 420,000 for incidental oral ingestion. All assessed residential exposures and risk estimates 

resulted in MOEs of >100; and therefore, are not of concern to HED. 

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

exposure assessment was also not performed for azoxystrobin at this time primarily because it 

has low vapor pressure (8.2x10-13 mm Hg). However, volatilization of pesticides may be a 

source of post-application inhalation exposure to individuals nearby pesticide applications. The 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 30 of 52

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, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report and may, as appropriate, develop policies and procedures to 

identify the need for and, subsequently, the way to incorporate post-application inhalation 

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

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

for azoxystrobin.

Table 6.2a. Short- and Intermediate-Term Incidental Oral Ingestion Exposure and Risk from Treated Indoor Surfaces.

Scenarios ISR (mg/cm2)

Short-Term 

PDR0-norm 

(mg/kg/day)

IntermediateTerm Potential 

Dose Rate (0-

norm 

(mg/kg/day))

Short-Term 

MOE

IntermediateTerm MOE

Hand-to-Mouth (vinyl/hard 

surfaces) 1.70E-03 0.089 0.042 280 480

Hand-to-Mouth (carpet/textile 

surfaces) 8.34E-04 0.089 0.042 280 480

*Although the intermediate-term MOEs are higher than the short-term MOEs, one should not assume that it is safer to be exposed for a longer 

duration. It is an artifact of dose spacing in toxicity studies, and conservative exposure assumptions.

Table 6.2b. Short- and Intermediate-Term Incidental Oral Ingestion Exposure and Risk from Treated Turf.

Scenarios TTR/GR/SR0 

(μg/cm2or g)

Short-Term PDR0-

norm (mg/kg/day)

Intermediate-Term 

PRD0-norm 

(mg/kg/day)

Short-Term 

MOE

IntermediateTerm MOE

Hand-to-Mouth 0.53 0.014 0.0067 1,800 3,000

Mouthing Grass 2.13 0.0035 0.0035 7,000 5,600

Soil Ingestion 7.1 0.000048 0.000048 530,000 420,000

Combined N/A 0.018 0.01 1,400 1,900

*Although the intermediate-term MOEs are higher than the short-term MOEs, one should not assume that it is safer to be exposed for a longer 

duration. It is an artifact of dose spacing in toxicity studies, and conservative exposure assumptions.

6.3 Combined Exposure

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

be combined and compared to the appropriate toxicity endpoint. Because no dermal endpoint 

was chosen for azoxystrobin, and inhalation post-application exposures are considered 

negligible, post-application residential exposure scenarios are not combined. In addition, 

residential handler and post-application scenarios generally should not be 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 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 31 of 52

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 

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 finds no changes that would affect 

the aggregate safety finding and confirms that there are no risks of concern resulting from postharvest use on tuberous and corm vegetables (subgroup 1C) dragon fruit, wasabi, the changes to 

the requested crop groups, 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 does 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 18% of the aPAD for the U.S. general population, and 

41.7% for the most highly exposed subgroup, children 1-2 years old. 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 32 of 52

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 (i.e. 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 adult (inhalation) aggregate MOE (for males and females) is 280, which indicates that

exposure and risk do not exceed HED’s level of concern (MOE <100). The aggregate MOE for 

children 1-2 years old, including incidental oral exposures from treated carpets and hard 

surfaces, is 210, which indicates that exposure and risk do not exceed HED’s LOC (MOE<100). 

Further refinement 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

Adult Males 25 100 1 0.012050 0.078 0.0901 280

Females 13-49 25 100 1 0.011208 0.078 0.089 280

Children 1-2 25 100 1 0.027847 0.089 0.117 210

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

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

3Residential Exposure = [Oral exposure + Inhalation Exposure]. Source of residential exposure values used in aggregate assessment (Table 6.1

and Table 6.2a).

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

5 Aggregate MOE = [NOAEL (Avg Food & Water Exposure + Residential Exposure)], NOAEL=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. However, intermediate-term exposure could be expected for children 

via incidental oral exposure from treated surfaces. The aggregate MOE for children 1-2 years

old, including incidental oral exposures from treated carpets and hard surfaces, is 360, which 

indicates that exposure and risk do not exceed HED’s LOC (MOE=100). Although intermediateterm MOEs are higher than the short-term MOEs, one should not assume that it is safer to be 

exposed for a longer duration. It is an artifact of dose spacing in toxicity studies, and 

conservative exposure assumptions. Further refinement could be made using anticipated 

residues, monitoring data, and additional % CT estimates, or more refined EDWCs may need to 

be incorporated in future assessments. 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 33 of 52

Table 7.3. Intermediate-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

Children 1-2 20 100 1 0.027847 0.042 0.070 360

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 

6.2a).

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

5

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 

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 Dragon Fruit, Wasabi, and Post-Harvest Potatoes, 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, 

DP390837, 12/01/2011.

- Azoxystrobin. Human Health Assessment Scoping Document in Support of Registration Review, B. 

O’Keefe, DP365660, 12/07/2009. 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 34 of 52

9.1 Short-/Intermediate-Term Handler Risk

Azoxystrobin is proposed for use as a foliar application to wasabi, dragon fruit and as a postharvest treatment to tuberous and corm vegetables (subgroup 1C). Application methods, 

maximum application rates and use sites are summarized in Table 3.3.1. Based on the proposed 

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

exposure during handling (mixing & loading) and post-application activities (sorting, packing 

and culling). 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). There are no requirements for personal protective equipment on either 

proposed label. 

HED evaluated the proposed uses and requested changes to the azoxystrobin crop group 

tolerances and determined that an ORE assessment is needed only for the post-harvest tuberous 

and corm (subgroup 1C) use. These new uses, and the uses included in the revised crop groups, 

have either been adequately assessed by HED or are expected to result in lower exposures than 

uses previously assessed. For a summary of recent ORE assessments, refer to the 2009 

azoxystrobin scoping document (B. O’Keefe, D365660, 12/07/2009). 

HED’s level of concern 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 occupational exposure. Occupational 

exposure and risk estimates resulting in MOEs greater than or equal to 100 will not be of concern 

to HED.

Summaries of the short- and intermediate-term risks for occupational handlers applying 

azoxystrobin to post-harvest tuberous and corm vegetables (subgroup 1C, represented by postharvest potato) are included in Table 9.1. No dermal hazard was identified for azoxystrobin, 

therefore, only a quantitative inhalation exposure assessment was performed. The results of the 

occupational handler exposure and risk assessment indicate that total short- and intermediateterm MOEs are not of concern to HED (i.e. an MOE > 100) with baseline attire. The short-term 

inhalation MOE for occupational application of azoxystrobin to post-harvest use sites was 

1,100,000. The intermediate-term MOE for occupational application of azoxystrobin to postharvest use sites was 910,000. 

Table 9.1. Occupational Handler Short- and Intermediate-Term Dermal and Inhalation Exposure and Risk Estimates for 

Post-Harvest Use 

Activity/Exposure 

Scenario

Solution 

Concentration2

(lb ai/gal soln)

Amount 

Treated per 

Day3

(1 gal/lbs of 

potatoes)

Amount 

Processed 

per Day4

(lbs 

boxes/hr)

Inhalation 

UE5(mg/lb 

ai)

ST & IT 

Inhalation 

Daily 

Dose6 (mg 

ai/kg/day)

ST MOE7 IT 

MOE8

Open 

Mixing/Loading 

Liquids

0.0195 1/4000 180,000 0.000219 0.000022 1,100,000 910,000

1. Liquid Formulation - Abound® Flowable Fungicide EPA Reg. No. 100-1098

2. Solution Concentration - fl oz product/gal water x lb ai/gal x 1 gal/128 fl oz (e.g. 0.6 fl oz/0.5 gal water x 2.08 lb ai/gal x 1 gal/128 oz)

3. Amount Treated Per day - gallons/lb of tubers (e.g. 0.5 gal treats 2,000 lb tubers = 1 gal/4,000 lb tubers). Provided by the registrant, in an email 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 35 of 52

correspondence.

4. Amount Processed per day - lbs boxes per hour. Assumed that a packing facility could potentially pack 2,000 boxes per hour, each weighing 90 

lbs (2,000 boxes/hr x 90 lbs each = 180,000 lbs boxes/hr)

5. Unit Exposure Values - Baseline (e.g. no respirator)

6. Short- a nd Intermediate Term Inhalation Daily Dose - [Amount Processed (lb boxes/hr) x Amount Treated daily (gal/lb) x soln concentration 

(lb ai/gal soln) x Unit Exposure x 8 (hr/day) x absorption factor (1.0)]/body weight

7. Short Term MOE - NOAEL (25 mg/kg/day)/Daily Dose (mg ai/kg/day)

8. Intermediate Term MOE - NOAEL (20 mg/kg/day)/Daily Dose (mg ai/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 involve postharvest applications, resulting in the potential for exposure to azoxystrobin during sorting, 

packing and culling treated vegetables. 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 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 primarily because of its low acute inhalation 

toxicity (Toxicity Category III), and low vapor pressure (8.2x10-13 mm Hg). 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 mixing/loading pesticides after harvest 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. 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.

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 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. 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 WPS does not apply to the post-harvest uses on citrus & tuberous and 

corm vegetables (subgroup 1C) addressed in this document, as outlined in 40 CFR 170.103(i) 

and 170.203(h). Workers should wait for the solution on the fruit/tubers to dry before engaging 

in post-application activities (such as packing, sorting and culling). Workers are assumed to be 

wearing baseline clothing while mixing/loading for post-harvest uses. 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 36 of 52

10.0 References

R. Baris, 11/28/11, DP#389703/394475, Drinking Water Exposure Assessment for New Uses of 

Azoxystrobin on Wasabi, Dragon-fruit and Sugarcane, and the Proposed Tolerances for Residues 

of Azoxystrobin for Use on Onion subgroups, Fruiting Vegetables Subgroups, Small Fruit & 

Berry Subgroups, Oilseed Subgroups; and the Proposed Increased Tolerance for Tuberous & 

Corm Vegetables Subgroup.

M. Negussie, 11/29/11, DP#390838, Azoxystrobin: Acute and Chronic Aggregate Dietary (Food 

and Drinking Water) Exposure and Risk Assessments for Section 3 Petition For Use On 

Tuberous and Corm Vegetables subgroup 1C (post-harvest); Dragon Fruit; Wasabi; and Crop 

Group/Subgroup Expansions for Bulb Vegetables 3-07A and 3-07B; Caneberries 13-07A; 

Bushberries 13-07B; Small Fruit Vine Climbing 13-07F, Except Fuzzy Kiwifruit; Low growing 

Berry 13-07G, Except Cranberry; Low Growing Berry 13-07H, Except Strawberry; Citrus Crop 

Group 10-10; Fruiting Vegetable Crop Group 8-10; and Oilseed Crop Group 20. 

M. Negussie, 11/16/11, DP#390152, Azoxystrobin. Section 3 Petition For Use On Potatoes 

(Post-harvest); Dragon Fruit; Wasabi; and Crop Group Expansions for Bulb Vegetables 3-07A 

and 3-07B; Caneberries 13-07A; Bushberries 13-07B; Small Fruit Vine Climbing 13-07F, 

Except Fuzzy Kiwifruit; Low growing Berry 13-07G, Except Cranberry; Low Growing Berry 

13-07H, Except Strawberry; Citrus Crop Group 10-10; Fruiting Vegetable Crop Group 8-10; 

and Oilseed Crop Group 20. Summary of Analytical Chemistry and Residue Data. 

B. O’Keefe, 12/07/09, DP#365660, Azoxystrobin. Human Health Assessment Scoping 

Document in Support of Registration Review. 

S. Piper, 04/30/08, DP#344389, Azoxystrobin. Human Health Risk Assessment for a Section 3 

New/Amended Uses on Non-grass Animal Feeds (Crop Group 18), Sorghum, Wheat, Cotton, 

and Wild Rice.

K. Rury, 12/01/11, DP#390837, Azoxystrobin. Occupational and Residential Exposure 

Assessment to Evaluate the Risk from Proposed Uses on Dragon Fruit, Wasabi, and Post-Harvest 

Potatoes, 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).

J. Wolf, 01/06/10, DP#371383, Drinking Water Assessment for amended label Quadris TopTM 

fungicide (EPA Reg. No. 100-1313) Azoxystrobin for use on golf course turf (only). 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 37 of 52

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

no

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

CR

-

-

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
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 38 of 52

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 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 39 of 52

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. 389702

Page 40 of 52

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 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 41 of 52

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 POW = 2.5

UV/visible absorption spectrum Not available
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 42 of 52

Appendix C. International Residue Limit Status Sheet.

Table C. Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

40 CFR 180. 507

Plants: 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)

benzeneacetate, including the isomer 

(Z)-

methyl 2-[[6-(2-cyanophenoxy)-4-

pyrimidinyl]

oxy]-α-

(methoxymethylene)benzeneacetate

Azoxystrobin. The 

residue is fat soluble.

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

US Canada Mexico2 Codex3

Berry, low growing, subgroup 13-

07G, except cranberry 10.0

3.0 lowbush blueberries, 

lingonberries

5 berries and other 

small fruits, except 

cranberry, grapes and 

strawberry

10 strawberry 

Bushberry subgroup 13-07B 5.0

3.0 bushberries (crop subgroup 

13-07B)

aronia berries, blueberries, 

buffalo currants, Chilean guava, 

currants, elderberries, European 

barberries, gooseberries, 

highbush blueberries, highbush 

cranberries, honeysuckle, 

huckleberries, jostaberries, 

lingonberries, lowbush 

blueberries, native currants, salal 

berries saskatoon berries 

(juneberries), sea buckthorn

5 berries and other 

small fruits, except 

cranberry, grapes and 

strawberry

Caneberry subgroup 13-07A 5.0

5.0 caneberries (crop subgroup

13-07A)

blackberries, loganberries, 

raspberries, wild raspberries

5 berries and other 

small fruits, except 

cranberry, grapes and 

strawberry

Cottonseed subgroup 20C 0.7 0.7 cotton seed

Dragon-fruit 2.0 2 mangoes 0.7 mango 
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 43 of 52

Table C. Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

Fruit, citrus, group 10-10 15.0

10 citrus fruits ; Australian 

desert limes, Australian finger 

limes, Australian round limes, 

Brown River finger limes, 

calamondins, citrus citrons, 

citrus hybrids, grapefruits, 

Japanese summer grapefruits, 

kumquats, lemons, limes, 

Mediterranean mandarins, 

mount White limes, new Guinea 

wild limes, oranges, pummelos, 

Russell River limes, Satsuma 

mandarins, sweet limes, 

tachibana oranges, Tahiti limes, 

tangelos, tangerines, tangors,

trifoliate oranges, uniq fruits

15 citrus fruits

Fruit small vine climbing, except 

fuzzy kiwifruit subgroup 13-07F 2.0 3 grapes 2 grapes

Onion, bulb, subgroup 3-07A 1.0 1.0 dry bulb onions 10 bulb vegetables

Onion, green, subgroup 3-07B 7.5 7.5 green onions

Pepper/eggplant subgroup 8-10B

3.0 2.0 bell peppers, eggplants, nonbell peppers, pepinos, pepper 

hybrids, 

3 fruiting vegetables 

other than cucurbits 

except mushrooms 

and sweet corn; 

30 peppers chili dried

Rapeseed subgroup 20A 1.0 1.0 rapeseeds (canola)

Sunflower subgroup 20B 0.5 0.5 sunflower seeds 0.5 sunflower seed

Tomato subgroup 8-10A

0.2

2.0 ground cherries, tomatillos 

0.2 tomatoes

0.6 tomato paste

3 fruiting vegetables 

other than cucurbits 

except mushrooms 

and sweet corn 

Vegetable, tuberous and corm, 

subgroup 1C 8.0

8.0 (vegetable, tuberous and 

corm, subgroup 1C (proposed)

0.03 potatoes

1 root and tuber 

vegetables

Wasabi, fresh 50 50 Herbs (crop subgroup 19A; 

fresh leaves)

70 herbs

Wasabi, dry 260 260 Herbs (crop subgroup 19A; 

dried leaves)

300 dried herbs 

(except hops (dry))

Completed: M. Negussie; 10/31/2011

1

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

not those proposed by the applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

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

processed post-harvest 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.
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 44 of 52

Appendix D. Azoxystrobin Metabolites
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 45 of 52
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 46 of 52
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 47 of 52
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 48 of 52
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 49 of 52
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 50 of 52

Appendix E. 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).
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 51 of 52

Appendix E. Screening Level Usage Analysis for Azoxystrobin
Azoxystrobin Human Health Risk Assessment DP No. 389702

Page 52 of 52