Azoxystrobin Human Health Risk Assessment DP Nos. D423691, D418374 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

MEMORANDUM 

DATE: April 7, 2015 

WASHINGTON, D.C. 20460 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Azoxystrobin. Human Health Aggregate Risk Assessment for Permanent 

Tolerances on Imported Asian Pear, Imported Tea, and Imported Coffee; 

Establishment of Permanent Tolerances on Ti Palm and for Crop Group 

Conversions for Stone Fruits Group 12-1 2 and Tree Nut Group 14-1 2 Crop 

Groups. 

PC Code: 128810 

Decision Nos.: 495749, 486446 

Petition Nos.: 3E8228; 4E83 I 9 

Risk Assessment Type: Single Chemical/Aggregate 

TXR No.: NA 

MRID No.: NA 

FROM: Kristin Rury, Risk Assessor 

Steve Funk, Senior Chemist 

DP Barcodes: 0423691 , 04 18374 

Registration Nos.: NA 

Regulatory Action: Section 3 Registration, Import Tolerances 

Case No.: 7020 

CAS No.: 131860-33-8 

40 CFR: § 180.507 

Whang Phang, Senior Toxicologist 

Risk Assessment Branch 3 (RAB 3) 

Health Effects Division (7509P) 

THROUGH: Christine Olinger, Branch Chief .f, r /3. ~ 'fl0 p,, 

Risk Assessment Branch 3 (RAB 3) r ~ 

Health Effects Division (7509P) 

TO: Rachel Holloman/Shaja Joyner 

Fungicide Herbicide Branch 

Registration Division (7505P) 

And 

Andrew Ertman/Barbara Madden 

Minor Use Branch 

Registration Division (7505P) 

Page 1 of 34 
Azoxystrobin Human Health Risk Assessμient DP Nos. D423691, D418374 

1.0 Executive Summary ....... .......... ......................................... .... ................................... .... .... .. 4 

2.0 HED Recommendations ....................................... ............ ........................... .... .... .... .... ... ... 7 

2.2 Tolerance Considerations ........... ... ........ .... .................................. .... .............................. 7 

2.2.1 Enforcement Analytical Method .......................... ....... .... .... ... ........ ................ ......... .... .. 7 

2.2.2 Recommended Tolerances ............................ ........ .................................. ........ .... ..... ...... 7 

2.2.3 Revisions to Petitioned-For Tolerances ............................................. ........................... 8 

2.2.4 International Harmonization ....... ...................................... ........ ........... ........................ 8 

3.0 Introduction ........ ................................................................................................................ 9 

3.1 Chemical Identity ........ ........... ... ................................................. ............ ........................ 9 

3.2 Physical/Chemical Characteristics ..... ................... ................................... .... .... .... .... .... 9 

3.3 Pesticide Use Pattern ............................................... ....... .... ............ .............................. 10 

3.4 Anticipated Exposure Pathways ........ .... .............................................. .... .... .... ........... 11 

3.5 Consideration of Environmental Justice .. ................... ............................................... 11 

4.0 Hazard Characterization and Dose-Response Assessment .................. .... .... ................ 12 

4.1 Summary of Toxicological Effects .............................................................................. 12 

4.2 Safety Factor for Infants and Children (FQPA Safety Factor) ... ............................ 13 

4.2.1 Completeness of the Toxicology Database ......................................................... .... .... 13 

4.2.2 Evidence of Neurotoxicity ........................................................................... ... ..... .... .... . 13 

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal .. ......... 13 

4.2.4 Residual Uncertainty in the Exposure Database ....................................................... 14 

4.3 Toxicity Endpoint and Point of Departure Selections ............................... .. ........... .. 14 

5.0 Dietary Exposure and Risk Assessment.. .......................... ............................................. 16 

5.1 Residues of Concern Summary and Rationale .......................................................... 16 

5.2 Food Residue Profile ............................ ...................... ................... ........ .... .... ............... 16 

5.3 Water Residue Profile ......................... ......................................................................... 17 

5.4 Dietary Risk Assessment ........................................................... ................... .... ............ 18 

5.4.1 Description of Residue Data Used in Dietary Assessment ........ ................................ 18 

5.4.2 Percent Crop Treated Used in Dietary Assessment.. ........ .... .... .......... .. .......... .... .. ... . 18 

5.4.3 Acute Dietary Risk Assessment.. ........... ................................................. ........ .... ......... 19 

5.4.4 Chronic Dietary Risk Assessment ............................................................................... 19 

5.4.5 Cancer Dietary Risk Assessment ..................... ........................................................... 19 

5.4.6 Summary Table .......................... ............... ................... ........ ............. ... ....... ................. 19 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization .. .................. ........ . 20 

6.1 Residential Bystander Post-application Inhalation Exposure ................................. 21 

6.2 Spray Drift ........................................................................ ........... ............... .................. 21 

7.0 Aggregate Exposure/Risk Characterization ......................... .... .... ........... .... .... .... .... .... .. 21 

7.1 Acute Aggregate Risk. ..... ....... ....... .... .... ... ........ ............................................................ 22 

7.2 Short-Term Aggregate Risk ....................................... .... ... ............ ........ .... ........ .... ...... 22 

7.3 Intermediate-Term Aggregate Risk ..................................................................... ...... 23 

7.4 Chronic Aggregate Risk .................. ....... ........ .... .... ... .... .... .... .... ....... ........ ................... 23 

7.5 Cancer Aggregate Risk ................................................................. .... .... .... .... ........ ....... 23 

8.0 Cumulative Exposure/Risk Characterization .......... ..................................................... 23 

9.0 Occupational Exposure/Risk Characterization .. ................... .... ................................... 23 

9.1 Short-/lntermediate-Term Handler Risk ................. ................... ............................... 23 

9.2 Short-/lntermediate-Term Post-Application Risk ............. .... .... ............................... 26 

9.2.1 Dermal Post-application Risk .............................................................................. ....... 26 

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Azoxystrobin Human Health Risk Assessment DP Nos. D423691, D418374

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9.2.2 Inhalation Post-application Risk................................................................................. 26

10.0 References......................................................................................................................... 27

Appendix A. Toxicology Profile................................................................................................ 29

A.1 Toxicology Data Requirements................................................................................... 29

A.2 Toxicity Profiles............................................................................................................ 30

Appendix B. Physical/Chemical Properties............................................................................. 33

Appendix C. Review of Human Research................................................................................ 34
Azoxystrobin Human Health Risk Assessment DP Nos. D423691, D418374

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1.0 Executive Summary

Azoxystrobin is a β-methoxyacrylate fungicide, currently registered for use on a variety of field, 

vegetable, fruit, and nut crops as well as on ornamental plants and turf. It is also used to control 

mold on indoor surfaces. Its biochemical mode of action is inhibition of electron transport. 

This document addresses two separate petitions: (1) one submitted by the Registrant, Syngenta 

Crop Protection, Inc (Syngenta) and (2) a second submitted by the Inter-Regional Research 

Project Number 4 (IR-4). These actions are summarized as follows: 

1. PP# 3E8228: Syngenta has submitted a proposal to add import tolerances without

domestic registrations to the AmistarZtra SC label (Columbia) on coffee, to the 

Azoxystrobin Amistar WP 10% label (South Korea) on Asian pear, and to the Amistar 20 

SC label (Japan) on tea. 

2. PP# 4E8319: IR-4 has submitted a proposal to add azoxystrobin use on Ti palm, and to 

incorporate recent revisions to the crop group listings of the Stone Fruits (Crop Group 12-

12) and Tree Nut (Crop Group 14-12) crop groups on the Abound® Flowable Fungicide 

label (EPA Reg. No. 100-1098). Abound® Flowable Fungicide is a liquid concentrate 

containing 22.9% ai.

This document assesses the exposures and risks from the proposed tolerances of azoxystrobin for 

domestic uses on Ti palm, stone fruits, and tree nuts and on imported coffee, tea, and Asian pear. 

HED has not previously assessed occupational exposure from azoxystrobin use on stone fruits or 

tree nuts with updated policies (i.e., new assumptions for unit exposures and acres treated); 

therefore, occupational exposure corresponding to the proposed crop group updates has been 

assessed according to current exposure policies. This document also reevaluates the existing 

residential scenarios for aggregate risk assessment because the points of departure (PODs) for 

azoxystrobin have recently changed. 

Proposed Use Profile

Azoxystrobin may be applied at a maximum single application rate of 20 fl oz/A (0.33 lb ai/A) to 

Ti palm leaves and roots, 12 fl oz/A (0.20 lb ai/A) to tree nuts, and 15.5 fl oz/A (0.25 lb ai/A) to 

stone fruits. The proposed labels require occupational handlers to wear long-sleeved shirts, long 

pants, shoes, socks, and chemical resistant gloves. The restricted entry interval (REI) listed on 

the Abound® label is 4 hours. 

Exposure Profile

Exposure to azoxystrobin can occur from dietary (food and drinking water), residential, and 

occupational exposure sources. Based on all of the proposed application rates and label 

information, only short- and intermediate-term dermal and inhalation exposures are expected for 

occupational handlers and post-application workers. Based on the existing residential uses of 

azoxystrobin on turf and ornamentals, only short-term dermal and inhalation exposures are 

expected for residential handlers. Short-term residential post-application exposure is expected 

for adults and children. For the proposed domestic uses of azoxystrobin, there is also potential 
Azoxystrobin Human Health Risk Assessment DP Nos. D423691, D418374

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for acute and chronic exposure through food and drinking water; and for the proposed import 

tolerances with no domestic registrations there is only potential through food. 

Toxicity/Hazard

The azoxystrobin database is complete and adequate for risk assessment. In repeat-dose oral 

studies, the liver and bile ducts were consistently the target organs of azoxystrobin toxicity. 

Developmental effects were not seen in rabbit or rat developmental toxicity studies. In the rat 

reproduction study, offspring and parental effects (decreased body weight and increased adjusted 

liver weight) were observed at the same dose. In a 21-day repeated dose dermal study in the rat, 

neither dermal nor systemic toxicity was seen at the limit dose (1,000 mg/kg/day). Furthermore, 

there was no concern for developmental or reproductive effects. Therefore, a hazard was not

identified for short- and intermediate-term dermal exposure scenarios, and a dermal risk 

assessment is not applicable at this time. The acute and chronic dietary points of departure 

(PODs) remain unchanged since the previous risk assessment. However, the inhalation and 

incidental oral PODs have been revised by since the previous assessment. For short- and 

intermediate-term incidental oral and inhalation exposures the POD has been revised to be based 

on the 2-generation reproduction study in rats. The POD is based on decreased pup weights in 

both males and females at the lowest observable adverse effect level (LOAEL) of 165 mg/kg/day 

(no observable adverse effect level (NOAEL) = 35 mg/kg/day). Since inhalation absorption data 

are not available, toxicity by the inhalation route is considered to be equivalent to the toxicity by 

the oral route of exposure. Azoxystrobin is characterized as "not likely" to be a human 

carcinogen. To account for the use of a LOAEL from the acute neurotoxicity study in rats, the 

Agency has applied a 3X Food Quality Protection Act (FQPA) Safety Factor (SF) will be 

adequate to extrapolate a NOAEL in assessing acute risk. The FQPA SF has been reduced to 1X 

for all other exposure durations. Azoxystrobin exhibits low acute mammalian toxicity via oral, 

dermal, and inhalation routes of exposure (Category III or IV for acute lethality and irritation 

studies) and is not a dermal irritant or sensitizer.

Dietary Exposure (Food and Water) and Risk Estimates 

Slightly refined acute and chronic dietary analyses were conducted for the proposed and existing 

uses of azoxystrobin. For both the acute and chronic assessments, the modeled surface water 

estimated drinking water concentration (EDWC) from the currently registered turf application 

scenario was the highest EDWC for all proposed/registered crops and was incorporated directly 

into the dietary assessment. 

The acute assessment incorporated tolerance-level residues for all commodities, except for citrus 

fruits (which used the highest residues from residue trials), assumed that 100% of the crops were 

treated (100% crop treated; CT), and incorporated default processing factors except for where 

tolerances were established for processed commodities or when processing studies showed no 

concentration. The results of the acute dietary analysis for food and drinking water indicate that 

acute dietary risks do not exceed the Agency’s level of concern (< 100% of the aPAD) for the 

U.S. population and all population subgroups. At the 95th percentile, the acute dietary (food and 

drinking water) risk estimates utilized 16% of the acute population adjusted dose (aPAD) for the 

general U.S. population and utilized 40% of the aPAD for children 1-2 years old, the most highly 

exposed subpopulation. 
Azoxystrobin Human Health Risk Assessment DP Nos. D423691, D418374

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The chronic dietary analysis incorporated tolerance-level residues, average %CT estimates when 

available, and default processing factors except for where tolerances were established for 

processed commodities or when processing studies showed no concentration. The chronic 

dietary (food and drinking water) risk estimates utilized 6.0% of the chronic population adjusted 

dose (cPAD) for the U.S. population and utilized 15% of the cPAD for the most highly exposed 

subgroup, children 1-2 years old. 

Aggregate Exposure and Risk Estimates

There is only potential for short-term aggregate exposure to azoxystrobin via the dietary and 

residential pathways; residential exposures include inhalation (adults and children) and incidental 

oral (only children 1 to <2 years). For adults and children 1 to <2 years, the short-term aggregate 

risk estimates are not of concern; the margins of exposure (MOEs) are 2,400 and 280, 

respectively. 

Occupational Exposure and Risk Estimates 

A short- and intermediate-term occupational risk assessment was performed for azoxystrobin use 

on Ti palm, stone fruits, and tree nuts. Based on the proposed use pattern of azoxystrobin, there 

is potential for short- and intermediate-term occupational exposure during handling (mixing, 

loading, and applying) and post-application activities. The occupational handler assessment is

based on inhalation exposures only, since dermal hazard was not identified. The results of the 

occupational handler risk assessment indicate that short- and intermediate-term inhalation MOEs 

are not of concern (i.e., MOEs ≥ 100) with baseline mitigation (no respirator) and engineering 

control for aerial applications (enclosed cockpits)). The MOEs range from 19,000 to 4,300,000 

for occupational handlers. 

Although occupational post-application dermal exposure is expected following treatment of 

agricultural crops, dermal hazard was not identified for azoxystrobin. Therefore, a quantitative 

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

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

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

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

inhalation exposure assessment for azoxystrobin.

Review of Human Research 

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

intentionally exposed to a pesticide or other chemical. These data, which include PHED 1.1; the 

AHETF database; the Residential SOPs, are (1) subject to ethics review pursuant to 40 CFR 26, 

(2) have received that review, and (3) are compliant with applicable ethics requirements. For 

certain studies, the ethics review may have included review by the Human Studies Review 

Board. Descriptions of data sources, as well as guidance on their use, can be found at the 

Agency website1. 

Environmental Justice 

 

1 http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html
Azoxystrobin Human Health Risk Assessment DP Nos. D423691, D418374

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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).

2.0 HED Recommendations

There are no deficiencies that would preclude establishing the recommended tolerances for 

azoxystrobin on the imported commodities: Asian pear, coffee, and tea. Additionally, there are 

no deficiencies that would preclude establishing the recommended tolerance for Ti palm and 

establishing crop group conversions for stone fruits group 12-12 and tree nut group 14-12. The 

specific tolerance recommendations are discussed in Section 2.2. 

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

A gas chromatography with a nitrogen-phosphorus detector (GC/NPD) method, RAM 243/04, is 

available for the enforcement of tolerances for residues of azoxystrobin and its Z-isomer in crop 

commodities. The method has undergone method validation by the Analytical Chemistry Branch 

(ACB)/Biological and Economic Analysis Division (BEAD). The method was revised to 

incorporate comments made by BEAD, and the revised method (designated RAM 243, dated 

5/15/98) has been submitted to FDA for inclusion in Pesticide Analytical Manual (PAM),

Volume II. The limit of quantification (LOQ) is 0.01 ppm for each analyte in crop commodities.

Data have previously been submitted pertaining to the multi-residue methods testing of 

azoxystrobin in conjunction with the grape petition (PP#5F4541). The data indicate that 

azoxystrobin could not be recovered through application of the multi-residue protocols. These 

data have been forwarded to the Food and Drug Administration (FDA) for inclusion in PAM I.

Azoxystrobin may be determined by QuEChERS. 

2.2.2 Recommended Tolerances

The residue definition (40CFR§180.507) complies with the recommendation of the S. Knizner 

5/27/09 memo; no change is needed. For compliance in plant commodities, the sum of 

azoxystrobin and its Z-isomer is determined.

Table 2.2.2. Tolerance Summary for Azoxystrobin

Commodity Proposed Tolerance 

(ppm)

HED-Recommended 

Tolerance (ppm)

Comments 

(correct commodity definition)

Coffee, bean, green 0.03 0.03 Coffee, green bean

Asian Pear 0.07 0.07 Pear, Asian

Tea 10.0 20.0 Tea, dried 

Ti palm, leaves 50 50.0 Ti, leaves

Translation of existing group 2 

(leaves of root and tuber 

vegetables) tolerance. 
Azoxystrobin Human Health Risk Assessment DP Nos. D423691, D418374

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Table 2.2.2. Tolerance Summary for Azoxystrobin

Commodity Proposed Tolerance 

(ppm)

HED-Recommended 

Tolerance (ppm)

Comments 

(correct commodity definition)

Ti palm, roots 0.5 0.5 Ti, roots

Translation of existing subgroup 

1A (root vegetable) tolerance.

Stone Fruit Group 12 Revoke Revoke Crop Group conversion to 12-12

Fruit, stone, Group 12-

12

2.0 2.0 Crop Group conversion.

Harmonization with Codex.

Nut, Tree, Group 14 Revoke Revoke Crop Group conversion to 14-12

Nut, tree, group 14-12 0.02 0.02 Nut, tree, group 14-12, except 

pistachio.

Crop Group conversion. 

Pistachio remains at a higher 

tolerance (0.50 ppm)

2.2.3 Revisions to Petitioned-For Tolerances

The proposed tolerance of 10.0 ppm for tea is insufficient, as the trials were conducted at 50% of 

the label maximum rate. Correction by proportionality to the maximum label rate provides a 

tolerance recommendation of 20 ppm.

2.2.4 International Harmonization

The residue definitions for plants and livestock are not harmonized with Codex; the US and the 

Canadian residue definitions include both the predominant E-isomer and the minor Z-isomer

whereas the Codex includes only the E-isomer.

A Codex Maximum Residue Limit (MRL) has been established for coffee beans at 0.03 mg/kg, 

but no MRLs have been established for Asian pear or tea. Codex recommended an increase in its 

coffee bean tolerance from 0.02 to 0.03 ppm in 2013. The recommended US tolerance for coffee 

is harmonized with Codex. No MRLs have been established in Canada for tea, coffee, or pears. 

Codex has not established an MRL for Ti palm leaves or roots. Canada has not established a 

tolerance for Ti palm leaves or roots. There is no issue of harmonization. 

For the crop group conversions, Codex has established an MRL for stone fruit at 2 mg/kg. 

Canada has a tolerance for peach at 0.8 ppm. For purposes of harmonization with Codex, the 

stone fruits group 12-12 will be increased to 2.0 ppm from the current tolerance of 1.5 ppm for 

stone fruits group 12.

Codex has established an MRL of 0.01 mg/kg for tree nuts. Canada has established tolerances of 

0.02 ppm for the various tree nuts, which is harmonized with the US. The US crop group 

tolerance is based on a residue definition of azoxystrobin plus the Z-isomer (R230310). 

Residues were <0.01 ppm for each component in the almond and pecan trials. Therefore, the 

tolerance estimate is 0.02 ppm, the sum of the components. The Codex residue definition is 

parent only, which support the 0.01 mg/kg MRL. The US tolerance cannot be harmonized with 

Codex.
Azoxystrobin Human Health Risk Assessment DP Nos. D423691, D418374

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3.0 Introduction

Azoxystrobin is a broad-spectrum fungicide and belongs to a class of pesticidal compounds 

called β-methoxyacrylates, which are derived from the naturally occurring strobilurins (Group 11 

fungicide). The biochemical mode of action is inhibition of electron transport. 

3.1 Chemical Identity

Table 3.1. Azoxystrobin Nomenclature.

Compound

Common name Azoxystrobin

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

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

methoxyacrylate

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. No. 100-1098) containing 22.9% ai

Regulated metabolite, Zisomer

Common name Azoxystrobin, Z-isomer

Company experimental name R230310

Chemical name methyl (2Z)-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 and is considered 

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

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

dermal absorption in the rat dermal penetration study. The physicochemical properties of 

azoxystrobin are summarized in Appendix B. 

N N

O O

CN OCH3

O

H3CO

N N

O O

CN

O OCH3

H3CO
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3.3 Pesticide Use Pattern

In addition to the domestic registrations outlined below, Syngenta has submitted a proposal to 

add import tolerances with no domestic registrations to the AmistarZtra SC label (Columbia) on 

coffee at a maximum single application rate of 0.14 lb ai/A, to the Azoxystrobin Amistar WP 

10% label (South Korea) on Asian pear at a maximum single application rate of 0.4 lb ai/A, and 

on tea to the Amistar 20 SC label (Japan) at a maximum single application rate of 0.39 lb ai/A. 

Table 3.3. Summary of Proposed Directions for Use of Azoxystrobin.

Applic. 

Timing, Type, 

and Equip.

Formulation Applic. 

Rate 

lb ai/A

Max. No. 

Applic. per 

Season

Max. Seasonal 

Applic. Rate

lb ai/A

PHI

(days)

Use Directions and 

Limitations

Import Tolerances without Domestic US Registration (PP# 3E8228)

1

Coffee

Foliar with 

ground 

equipment.

AmistarZtra

SC

(200 g/L 

azoxystrobin;

80 g/L

Cyproconazole)

Colombia

0.089-

0.14 3 0.402 15

Start application 90 days 

after principal flowering 

followed by 2 

consecutive applications 

with a 45 day interval. 

Use a mixture volume of 

50 cc per tree after 

diluting 1.8 ml of 

commercial product to 1 

liter of water. Apply 

when the coffee crop 

(leaves, branches, and 

fruits) is dry. The 

reentry interval is 4 

hours.

Asian Pear

Foliar

Azoxystrobin Amistar 

WP 10%

(South 

Korea)

0.403 5 2.0 7

Apply at beginning of 

infestation with a 10 day 

retreatment interval.

Tea

Foliar

Amistar 20 

SC

(0.22 kg/L)4

0.098-

0.39 3 1.17 14

Dilution rate 1 g product 

per 1 L water. Apply 

mixture at a maximum 

of 4000 L/ha.

Domestic US Registrations/Crop Group Conversions Proposed By IR-4 (PP# 4E8319)

Ti Palm

Foliar

Abound 

Flowable

(EPA Reg.

No. 100-

1098)

(2.08 lb/gal)

0.10-

0.33

Not 

specified 2.00 0

Soil Abound 

Flowable

0.0065-

0.013 lb 

ai/1000 

row feet

Not 

specified 2.00 0

Band application 

between rows.
Azoxystrobin Human Health Risk Assessment DP Nos. D423691, D418374

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Table 3.3. Summary of Proposed Directions for Use of Azoxystrobin.

Applic. 

Timing, Type, 

and Equip.

Formulation Applic. 

Rate 

lb ai/A

Max. No. 

Applic. per 

Season

Max. Seasonal 

Applic. Rate

lb ai/A

PHI

(days)

Use Directions and 

Limitations

(EPA Reg. 

No. 100-

1098)

(2.08 lb/gal)

Use for 

soilborne/seedling 

disease control.

Apply in a minimum of 

10 gallons per acre

Tree Nuts

Foliar

Abound® 

Flowable

(EPA Reg.

No. 100-

1098)

(2.08 lb/gal)

0.195 Not 

Specified 1.2 45 Apply every 7-21 days

Stone Fruits (Crop Group 12-12)

Foliar

Abound® 

Flowable

(EPA Reg. 

No. 100-

1098)

(2.08 lb/gal)

0.25 Not 

Specified 1.5 0 Apply every 7-14 days

1Based on foreign label translations provided in Section B of the petition. There are no domestic registrations for 

the proposed new uses on coffee, Asian pear, and tea.

2Calculated based on a maximum of 8333 trees per ha.

31 g product is diluted to 1 liter. Calculated from an application of 4500 liters spray solution per ha.

4Density 1.1 g/cm3

.

3.4 Anticipated Exposure Pathways

Humans may be exposed to azoxystrobin in food and drinking water since azoxystrobin may be 

applied directly to growing crops and application may result in azoxystrobin reaching surface 

and ground sources of drinking water. In an occupational setting, applicators 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 fields. 

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

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

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

exposure assessment. 

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

(http://www.epa.gov/environmentaljustice/resources/policy/exec_order_12898.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 
Azoxystrobin Human Health Risk Assessment DP Nos. D423691, D418374

Page 12 of 34

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 U.S. Department of 

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

(NHANES/WWEIA) and are used in pesticide risk assessments for all registered food uses of a 

pesticide. These data are analyzed and categorized by subgroups based on age and ethnic group. 

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

exposure assessments are performed when conditions or circumstances warrant. Whenever 

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

for adult applicators and for toddlers, youths, and adults entering or playing on treated areas 

post-application are evaluated. Spray drift can also potentially result in post-application 

exposure and it is also being considered whenever appropriate. Further considerations are also 

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

specialized software and models that consider exposure to other types of possible bystander

exposures and farm workers as well as lifestyle and traditional dietary patterns among specific 

subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

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

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

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

poses a human health hazard. Since the previous assessment, the inhalation and incidental oral 

PODs have been revised and the changes have been summarized below; all other PODs have 

remained unchanged since the previous assessment. 

4.1 Summary of Toxicological Effects

Repeated oral dosing of azoxystrobin resulted in decreased body weights, decreased food intake 

and utilization, increased diarrhea, and other clinical toxicity observations (increased urinary 

incontinence, hunched postures, and distended abdomens) in rats. In addition, liver effects,

characterized by increased liver weights, increased serum levels of alkaline phosphatase and 

gamma glutamyltransferase, decreased serum levels of albumin, and gross and histological 

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

were found after oral administration. 

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

levels tested including the LOAEL. Decreases in body weight and food utilization were noted in 

the rat subchronic neurotoxicity study. There were no indications of treatment-related 

neurotoxicity in either the acute or subchronic neurotoxicity studies. 

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

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

exhibited decreased body weight gain. No adverse treatment-related developmental effects were 

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

weight and increased adjusted liver weight) were observed at the same dose.
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There was no evidence of carcinogenicity in rats and mice. As a result, EPA has classified 

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

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

expected to be expressed in whole animals.

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

is not an eye or skin irritant and is not a skin sensitizer.

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

EPA has retained an FQPA SF of 3X, in assessing acute dietary risk to account for the use of a 

LOAEL from the acute neurotoxicity study in rats in deriving the acute reference dose used for 

assessing acute dietary exposure for all populations including infants and children. The Agency 

believes that a 3X FQPA SF (as opposed to a 10X) will be adequate to extrapolate a NOAEL in 

assessing acute risk based on the following considerations:

a. the LOAEL is based on a transient effect (diarrhea in rats) expected to be 

relatively insignificant in nature. This effect is also seen in other chemicals of the 

same class;

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

studies using repeat dosing through dietary administration in rats or mice, and not 

through gavage dosing in rabbits; and 

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

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

Furthermore, EPA has determined that for short-term, intermediate-term and chronic risk 

assessments the available data show that it would be safe for infants and children to reduce the 

FQPA SF to 1X. These determinations are also based on the considerations in the sections 

below: 

4.2.1 Completeness of the Toxicology Database

The toxicity database for azoxystrobin is complete and adequate for risk assessment. A 

subchronic inhalation toxicity study (TXR# 0056307) and an immunotoxicity study (TXR# 

0057071) are not required for azoxystrobin at this time. 

4.2.2 Evidence of Neurotoxicity

Clinical signs, including transient diarrhea and decreased body weight, body weight gain, and 

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

considered indicative of neurotoxicity; there were no other effects seen in those studies that 

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

or additional uncertainty factors to account for neurotoxicity.

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal
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There is no evidence that azoxystrobin results in increased quantitative sensitivity to developing 

fetuses in rats or rabbits in the prenatal developmental studies or in young rats in the 2-

generation reproduction study. In the reproduction study, the offspring and the parental effects 

occurred at the same dose level.

4.2.4 Residual Uncertainty in the Exposure Database

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

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

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

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

upper-bound inputs including assuming 100% of the proposed and registered crops treated, and 

tolerance-level residues for all existing and proposed commodities, except citrus fruits where the 

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

was partially refined, and used tolerance-level residues for all commodities and (% CT) estimates 

when available (Screening Level Usage Analysis (SLUA), 10/14/14). Although the acute and 

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

ensures that actual exposures/risks from residues in food will not be underestimated. The 

drinking water assessment utilized water concentration values generated by models and 

associated modeling parameters which are designed to produce conservative, health protective, 

high-end estimates of water concentrations which are not likely to be exceeded. The dietary 

(food and drinking water) exposure assessment does not underestimate the potential exposure for 

infants, children, or women of child bearing age. 

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

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

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

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

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

4.3 Toxicity Endpoint and Point of Departure Selections

A detailed hazard characterization and a discussion of the POD selection is presented in the 

previous azoxystrobin risk assessment (K. Rury, D389702, 01/18/2012). The inhalation and 

incidental oral PODs have been revised by the risk assessment team since the previous 

assessment. For short- and intermediate-term incidental oral and inhalation exposures, the POD 

is now based on the 2-generation reproduction study in rats. For incidental oral and inhalation 

exposures, the results from the 2-generation reproduction study in rats were selected to establish 

the toxicity endpoints and PODs for short-and intermediate-term exposures. There are three 

candidate studies to be considered for selecting PODs for incidental oral and inhalation risk

assessment because the durations of exposure and sensitivity of the effects are relevant. The 

NOAELs of these three studies are very similar as indicated below: 
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NOAEL (mg/kg/day) LOAEL (mg/kg/day)

2-generation reproduction-rats 35 (offspring) 165 (offspring)

Developmental toxicity-rats 25 100

90-Day oral toxicity – rats 20 211

The NOAEL (35 mg/kg/day) from the reproduction study, where the pups were adversely 

affected as demonstrated by decreased in pup body weight at various intervals ranging from 8-

21% relative to the controls, will be protective of the effects seen in the developmental toxicity 

study (LOAEL = 100 mg/kg/day) and in the 90-day oral toxicity study (LOAEL=211 

mg/kg/day). The difference in the NOAELs derived from these three studies were also 

influenced by the dose selection. Therefore, the NOAEL of 35 mg/kg/day of the developmental 

study was selected as the POD for incidental oral and inhalation risk assessments. Since 

inhalation absorption data are not available, toxicity by the inhalation route is considered to be 

equivalent to the toxicity by the oral route of exposure. 

Azoxystrobin is characterized as "not likely" to be a human carcinogen, and a cancer risk 

assessment is not needed. 

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

1

Exposure/

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, Level of 

Concern for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary

(All 

Populations)

LOAEL = 200 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 

3X

Acute RfD = 

0.67mg/kg/day

aPAD = 0.67

mg/kg/day

Acute Neurotoxicity - Rat. LOAEL 

= 200 mg/kg/day based on diarrhea 

at two-hours post dose at all dose 

levels tested.

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) & 

Intermediateterm (1-6 

months)

NOAEL = 35 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 

1X

Residential LOC for 

MOE = 100

2-generation reproduction study –

rats 

LOAEL = 165 mg/kg/day based on 

decreased pup weights in both males 

and females (↓8-21%).

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).

Inhalation2

Short-Term 

(1-30 days) &

IntermediateTerm

(1-6 months)

Oral NOAEL3

= 35

UFA = 10X

UFH = 10X

FQPA SF = 

1X

Occupational & 

Residential LOC for 

MOE = 100

2-generation reproduction study –

rats 

LOAEL = 165 mg/kg/day based on 

decreased pup weights in both males 

and females (↓8-21%).
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Table 4.3.1. Summary of Toxicological Doses and Endpoints for Azoxystrobin for Use in Dietary, NonOccupational and Occupational Human Health Risk Assessments.

1

Exposure/

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, Level of 

Concern for Risk 

Assessment

Study and Toxicological Effects

Cancer

(oral, dermal, 

inhalation)

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

1. Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response 

data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally 

relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse 

effect level. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = 

potential variation in sensitivity among members of the human population (intraspecies). FQPA SF = FQPA 

Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin 

of exposure. LOC = level of concern. N/A = not applicable.

2. To protect for the body weight decreases seen in the pups, a 69 kg body weight was used for estimating shortand intermediate-term inhalation doses because the pup body weight decrease also influenced by the maternal 

health. 

3. Toxicity via the inhalation route is assumed to be equivalent to the oral route.

5.0 Dietary Exposure and Risk Assessment 

5.1 Residues of Concern Summary and Rationale

The residues of concern for dietary risk assessment and the tolerance expression are summarized 

in Table 5.1. The residue definition and residues of concern have not changed since the previous 

risk assessment. Further information on the metabolism and degradation may be found in the 

HED Metabolism Assessment Review Committee Decision memo (W. Wassell, D251683, 

12/30/1998). 

Table 5.1. Summary of Metabolites and Degradates to be included in the Risk Assessment and 

Tolerance Expression for Azoxystrobin1

Matrix Residues included in Risk 

Assessment

Residues included in Tolerance 

Expression

Plants Primary Crop Azoxystrobin + Z-isomer Azoxystrobin + Z-isomer

Rotational Crop Azoxystrobin + Z-isomer Azoxystrobin + Z-isomer

Livestock Ruminant Azoxystrobin Azoxystrobin

Poultry Azoxystrobin Azoxystrobin

Drinking Water Azoxystrobin Not Applicable

1 HED Metabolism Assessment Review Committee Decision Memo; D251683, 12/30/98, W. Wassell

5.2 Food Residue Profile

There are adequate residue data on plant food and feed commodities for the purposes of risk 

assessment and tolerance assessment. 

New food commodity uses for azoxystrobin include Asian pear, tea, coffee, and Ti palm leaves 

and roots. These contribute minor incremental increases in exposure. There are no significant 

differences from prior assessments.
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Crop field trials generally reflect foliar applications with some soil applications (e.g., Ti palm). 

Residues from foliar applications are generally quantifiable and significant. Residues do 

concentrate in some processed commodities such as oils (peanut oil) and reduced water content 

commodities (tomato paste). However, residues did not concentrate in instant coffee or roasted 

coffee beans. Trials with banana and citrus fruits indicate that the residues remain mainly on the 

surface (peel) and do not extensively translocate. Residues also decline with time.

Livestock feeding studies indicate low transfer of residues to meat and milk with the highest 

transfer in liver. Quantifiable residues were not found in any poultry commodities.

Storage stability studies show that azoxystrobin and its Z-isomer are stable on food commodities 

stored under frozen conditions for extended periods (1 to 2 years). The available studies cover 

all existing crop field trial studies supplied in support of tolerance requests.

The metabolism in rotational crops is similar to that in primary crops but with larger amounts of 

conjugated metabolites than found in the primary rotational crop studies. Residues are very low 

in rotational crops, and the plant-back interval is 0 days for all crops with registered uses, except 

buckwheat and millet.

5.3 Water Residue Profile

The drinking water residues for the proposed uses of azoxystrobin were provided by the 

Environmental Fate and Effects Division (EFED) (Ibrahim Abdel-Saheb, D422726, 09/11/2014)

including use of the new surface and ground water models (Surface Water Concentration 

Calculator; SWCC, and Pesticide Root Zone Model - Ground Water; PRZM-GW). EFED 

estimates drinking water concentrations of a chemical based on the highest rate of application of 

the chemical on all registered and proposed crops. Existing uses on turf result in the highest 

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

applications) (T. Nguyen; D278783, D279444, and D279561; 02/04/2002). Therefore, EFED 

recommended that the EDWCs from turf use be incorporated into the dietary exposure 

assessment for the proposed uses of azoxystrobin, as they are the most conservative. Water 

residues were incorporated in the Dietary Exposure Evaluation Model software with the Food 

Commodity Intake Database (DEEM-FCID) into the food categories “water, direct, all sources” 

and “water, indirect, all sources.” 

Table 5.3. Estimated Drinking Water Concentrations (EDWCs) For Use in Azoxystrobin Dietary 

Assessment.

Scenario

Model

(application rate lb ai/A, 

frequency, interval)

Surface Water

(μg/L) 1

Ground Water 

(μg/L) 

(Acute/Chronic)

Peak

(1-in-10 yr)

365-day 

Average

(1-in-10 yr)

Entire 

Simulation 

Mean

SCI-GROW2

Turf

SWCC

(0.55, 9x, 10 d)

70.2 48.5 38.5 3.1

1 Bolded values are recommended for use in the human health risk assessment

1 SCI-GROW = Screening Concentration In Ground Water
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5.4 Dietary Risk Assessment

Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments 

were conducted using DEEM-FCID Version 3.16, which is based on NHANES 2-day food 

consumption data from 2003-2008. 

5.4.1 Description of Residue Data Used in Dietary Assessment

A slightly refined acute dietary analysis was conducted. The assumptions of the dietary 

assessment included tolerance-level residues for all commodities except citrus fruits (which used 

the highest residues from residue trials) and 100% CT for all crops. DEEM default processing 

factors were assumed except for where tolerances were established for processed commodities or 

when processing studies showed no concentration. Field trial data were translated from the 

representative commodities to the non-representative commodities according to HED SOP 

2000.1:”Guidance for Translation of Field Trial Data from Representative Commodities in the 

Crop Group Regulation to other Commodities in Each Crop Group/Subgroup.”

The chronic assessment was based on the assumption of tolerance-level residues for all 

commodities and average percent crop treated (%CT) estimates when available (J. Alsadek, 

SLUA, 10/14/2014). DEEM default processing factors were assumed except for where 

tolerances were established for processed commodities or when processing studies showed no 

concentration. 

The addition of coffee, tea, and Asian pears does not alter the dietary burdens of azoxystrobin to 

ruminants or poultry, and the existing tolerances for ruminant commodities will not be exceeded 

with the proposed uses on coffee, tea, and pears. 

The modeled surface water EDWC from the turf application scenario (currently registered) was 

incorporated directly into the dietary assessments (highest EDWC for all proposed/registered 

crops). The highest estimates for acute exposure, 70.2 ppb, and chronic exposure, 48.5 ppb, 

were used in the analysis. The new uses on Asian pears, tea, and coffee do not impact the water 

values, as there are no requested domestic uses.

5.4.2 Percent Crop Treated Used in Dietary Assessment

The acute assessment assumed that 100% of the proposed and existing crops were treated with 

azoxystrobin. However, the following average percent crop treated (%CT) estimates were used 

in the chronic dietary risk assessments for the following currently registered crops (J. Alsadek, 

SLUA, 10/14/2014): almonds, 20%; apricots, 10%; artichokes, 20%; asparagus, <2.5%; barley, 

<2.5%; green beans, 15%; blueberries, 15%; broccoli, 10%; cabbage, 10%; caneberries, 5%; 

cantaloupes, 20%; carrots, 10%; cauliflower, <2.5%; celery, 10%; corn, <2.5%; cotton, <2.5%; 

cotton (seed treatment), 25%; cucumbers, 20%; dry beans/peas, <2.5%; eggplant, 30%; garlic, 

70%; grapefruit, 20%; grapes, 5%; hazelnuts, 5%; lemons, <2.5%; lettuce, <2.5%; nectarines, 

<2.5%; onions, 5%; oranges, 5%; peaches, 5%; peanuts, 20%; peanuts (seed treatment), 30%; 

green peas, <2.5%; pecans, 5%; peppers, 20%; pistachios, 5%; plums/prunes, <2.5%; potatoes, 

40%; potatoes (seed treatment), <1%; pumpkins, 20%; rice, 40%; soybeans, 5%; soybeans (seed 
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treatment), <1%; spinach, 10%; squash, 20%; strawberries, 25%; sugar beets, 10%; sugar beets 

(seed treatment), <2.5%; sweet corn, 15%; tangelos, 25%; tangerines, 10%; tobacco, 15%; 

tomatoes, 25%; walnuts, >2.5%; watermelons, 15%; wheat, 5%; wheat seed (seed treatment), 

<1%. For all other crops in the chronic assessment, 100% CT was assumed.

5.4.3 Acute Dietary Risk Assessment

The results of the acute dietary analysis for food and drinking water indicate that acute dietary 

risks do not exceed the Agency’s level of concern (< 100% of the aPAD) for the U.S. population 

and all subgroups. At the 95th percentile, the acute dietary (food and drinking water) risk 

estimates utilized 16% of the acute population adjusted dose (aPAD) for the general U.S. 

population and utilized 40% of the aPAD for children 1-2 years old, the most highly exposed 

population subgroup. 

5.4.4 Chronic Dietary Risk Assessment

The results of the chronic dietary analysis for food and drinking water indicate that chronic

dietary risks do not exceed the Agency’s level of concern (< 100% of the aPAD) for the U.S. 

population and all subgroups. The chronic dietary (food and drinking water) risk estimates 

utilized 6.0% of the chronic population adjusted dose (cPAD) for the U.S. population and 

utilized 15% of the cPAD for the most highly exposed population subgroup, children 1-2 years

old. 

5.4.5 Cancer Dietary Risk Assessment

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

dietary exposure assessment was not performed. 

5.4.6 Summary Table

Table 5.4.6. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Azoxystrobin. 

Population Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary

Dietary Exposure 

(mg/kg/day) % aPAD Dietary Exposure(mg/kg/day) % cPAD

General U.S. Population 0.110459 16 0.010724 6.0

All Infants (< 1 year old) 0.131716 20 0.017593 9.8

Children 1-2 years old 0.269743 40 0.027728 15

Children 3-5 years old 0.228330 34 0.022261 12

Children 6-12 years old 0.129649 19 0.013336 7.4

Youth 13-19 years old 0.094863 14 0.008376 4.7

Adults 20-49 years old 0.096366 14 0.009213 5.1

Adults 50+ years old 0.089088 13 0.009308 5.2
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Table 5.4.6. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Azoxystrobin. 

Population Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary

Dietary Exposure 

(mg/kg/day) % aPAD Dietary Exposure(mg/kg/day) % cPAD

Females 13-49 years old 0.097704 15 0.008883 4.9

The values for the highest exposed population for each type of risk assessment are bolded.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

This document addresses the proposed new agricultural uses of azoxystrobin; therefore, new 

residential exposure is not expected. However, there are currently registered uses of 

azoxystrobin by both commercial and residential handlers on residential use sites, including turf, 

ornamentals, indoor uses (carpet and hard surfaces), and in paints. Each of these existing 

residential use patterns has previously been re-assessed by HED to incorporate up to date 

policies in the Residential SOPs (K. Rury, D294387, 03/30/2012). Furthermore, the inhalation 

and incidental oral PODs have changed since the previous assessment. Therefore, the scenarios 

for aggregate risk assessment have been updated to account for these changes. 

Table 6.0 reflects the residential risk estimates that are recommended for use in the aggregate 

assessment for azoxystrobin. The proposed uses do not impact the aggregate risk assessment; 

however, the scenarios that do impact the aggregate assessment have been re-evaluated in this 

assessment to reflect the revised incidental oral and inhalation PODs. 

 The recommended residential exposure for use in the adult aggregate assessment reflects 

inhalation exposure from handlers applying paint via airless sprayers.

 The recommended residential exposure for use in the children 1 to <2 years old aggregate 

assessment reflects inhalation and hand-to-mouth exposures from post-application 

exposure to indoor applications to carpets.

Table 6.0. Recommendations for the Residential Exposures for the Azoxystrobin Aggregate Assessment.1

Lifestage

Handler Exposure 

(mg/kg/day)2 Residential 

Handler Total 

MOE3

Post-application Exposure 

(mg/kg/day)

Residential Postapplication Total 

Exposure 

(mg/kg/day)4

Residential Postapplication 

MOE5

Inhalation Inhalation Oral

Short-Term

Adult 

0.0041

(Inhalation 

Handler Exposure 

- Airless Paint 

Sprayers)

8,600 N/A N/A N/A N/A

Child 1 to 

<2 years old N/A N/A

0.00000000048

(Post-application 

Inhalation, Surface 

Directed Sprays) 

0.0983

(Hand-toMouth 

from 

Indoor 

Application 

to Carpets)

0.0983 360

1 N/A = not applicable. Adult post-application exposures do not need to be aggregated with the handler exposures, and children 

handler exposures are not expected. For adults, the residential total exposure is equivalent to the inhalation exposure (Table 

5.1). For children 1 to < 2 years old, total residential exposure combines high-end inhalation and post-application incidental 

oral exposure (Table 5.2). These tables are located in DP394287 (K. Rury, 03/30/2012).

2 Handler exposure represents high-end handler exposure (i.e. the highest handler exposure of all scenarios assessed).
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3 Total MOE = Inhalation MOE = NOAEL / Inhalation Exposure. Short-Term Inhalation NOAEL = 35 mg/kg/day.

4 Post-application exposure represents high-end inhalation and/or incidental oral exposure for the relevant exposure duration.

5 Total MOE = NOAEL ÷ (Inhalation Exposure + Incidental Oral Exposure). Inhalation NOAEL & Incidental Oral NOAEL = 

35 mg/kg/day.

6.1 Residential Bystander Post-application Inhalation Exposure

Volatilization of pesticides may be a source of post-application inhalation exposure to 

individuals nearby pesticide applications. The agency sought expert advice and input on issues 

related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 

Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on 

March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The 

agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a 

subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). During Registration 

Review, the agency will utilize this analysis to determine if data (i.e., flux studies, route-specific 

inhalation toxicological studies) or further analysis is required for azoxystrobin.

A quantitative residential post-application inhalation exposure assessment was completed as part 

of this assessment to re-evaluate the scenarios for aggregate risk assessment using the revised 

inhalation POD. The screening-level indoor inhalation post-application MOEs for surface 

directed applications were 73,000,000,000 (children 1 to < 2 years old) and 270,000,000,000 

(adults). 

6.2 Spray Drift

Spray drift is a potential source of exposure to those nearby pesticide applications. This is 

particularly the case with aerial application, but, to a lesser extent, spray drift can also be a 

potential source of exposure from the ground application methods (e.g., groundboom and 

airblast) employed for azoxystrobin. The agency has been working with the Spray Drift Task 

Force (a task force composed of various registrants which was developed as a result of a Data 

Call-In issued by EPA), 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). 2 The agency has also developed a policy on how to 

appropriately consider spray drift as a potential source of exposure in risk assessments for 

pesticides. The potential for spray drift will be quantitatively evaluated for each pesticide during 

the Registration Review process which ensures that all uses for that pesticide will be considered 

concurrently. The approach is outlined in the revised (2012) Standard Operating Procedures 

For Residential Risk Assessment (SOPs) - Residential Exposure Assessment Standard Operating 

Procedures Addenda 1: Consideration of Spray Drift. This document outlines the quantification 

of indirect non-occupational exposure to drift. 

7.0 Aggregate Exposure/Risk Characterization

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 

 

2 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
Azoxystrobin Human Health Risk Assessment DP Nos. D423691, D418374

Page 22 of 34

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 utilized the Residential Standard Operating Procedures (SOPs) implemented 

in January of 2012 and the updated PODs for incidental oral and inhalation scenarios. HED 

confirms that there are no risks of concern resulting from the proposed or existing uses of 

azoxystrobin. 

7.1 Acute Aggregate Risk

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

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

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

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

water exposure estimates are 16% of the aPAD for the general U.S. population, and 40% for the 

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

7.2 Short-Term Aggregate Risk

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

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

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

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

residential exposure scenarios considered in the aggregate assessment, see K. Rury, D394287, 

03/30/2012.

The general US population (inhalation) aggregate MOE is 2,400. Therefore, adult aggregate

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

1-2 years old, including incidental oral exposures from treated carpets, is 280, which indicates 

that aggregate exposure and risk is greater than 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- and Intermediate Term Aggregate Risk Calculations.

Population

Short- and Intermediate-Term Scenarios

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

Adults 35 100 0.35 0.010724 0.0041 0.014824 2,400

Child 35 100 0.35 0.027728 0.0983 0.126028 280

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

2 Maximum Allowable Exposure (mg/kg/day) = NOAEL (35 mg/kg/day)/LOC (100). 
Azoxystrobin Human Health Risk Assessment DP Nos. D423691, D418374

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3 Residential Exposure = [Oral exposure + Inhalation Exposure]. For updated residential scenarios for aggregate risk 

assessment, see K. Rury, D418012 and D423961, 12/17/2014. 

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

5 Aggregate MOE = [NOAEL (35 mg/kg/day)/ (Avg Food & Water Exposure + Residential Exposure)]. 

7.3 Intermediate-Term Aggregate Risk

Intermediate-term residential exposure is not expected for azoxystrobin due to the intermittent 

application by homeowners. Therefore, the intermediate-term aggregate risk would be 

equivalent to the chronic dietary exposure estimate. 

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

This document presents an assessment of the proposed uses of azoxystrobin on Ti palm, stone 

fruits, and tree nuts. HED has not previously assessed azoxystrobin use on stone fruit or tree 

nuts with the new unit exposure and acres treated assumptions, so occupational exposure 

corresponding to the proposed crop group updates has been assessed according to current 

exposure policies. 

9.1 Short-/Intermediate-Term Handler Risk
Azoxystrobin Human Health Risk Assessment DP Nos. D423691, D418374

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There is potential for short- and intermediate-term occupational exposure to azoxystrobin during 

both handler [mixing, loading, and application (via the dermal and inhalation routes)] and postapplication activities (via the dermal route) based on the proposed uses.

The occupational handler assessment is based on inhalation exposures only since no dermal 

hazard was identified. Additionally, for inhalation exposures, the POD selected is considered 

protective of both short- and intermediate-term durations. The results of the occupational handler 

risk assessment indicate that short- and intermediate-term inhalation MOEs are not of concern 

(i.e., MOEs > 100) with baseline mitigation (no respirator) and engineering control for aerial 

applications (enclosed cockpits)). The MOEs range from 19,000 to 4,300,000 for occupational 

handlers. 
Azoxystrobin Human Health Risk Assessment DP Nos. D423691, D418374

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Table 6.1.1. Occupational Handler Non-Cancer Short- and Intermediate-Term Exposure and Risk Estimates for Azoxystrobin.

Exposure Scenario Crop or Target LOC

Inhalation Unit 

Exposure (μg/lb 

ai)1 Maximum

Application Rate

Area Treated 

or Amount 

Handled Daily2

Inhalation

Baseline Dose 

(mg/kg/day)3 MOE4

Mixer/Loader

Mixing/Loading Liquids for 

Aerial Application

Orchard Crops5

100 0.219 0.33 lb ai/A 350 0.00037 95,000

Mixing/Loading Liquids for 

Airblast Application

Orchard Crops5

100 0.219 0.33 lb ai/A 40 acres 0.000042 840,000

Mixing/Loading Liquids for 

Chemigation Application

Orchard Crops5

100 0.219 0.33 lb ai/A 350 acres 0.00037 95,000

Applicator

Aerial Application Orchard Crops5 100 0.0049 0.33 lb ai/A 350 acres 0.0000082 4,300,000

Airblast Application Orchard Crops5 100 4.71 0.33 lb ai/A 40 acres 0.000901 39,000

Flagger

Flagging for Aerial 

Application Orchard Crops5 100 0.35 0.33 lb ai/A 350 acres 0.00059 720,000

Mixer/Loader/Applicator

Mixing/Loading/Applying 

with Mechanically 

Pressurized Handgun –

Foliar & Ground Directed

Orchard Crops5

100 3.9 0.033 lb ai/A 1000 gal 0.0018 19,000

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table”; Level of mitigation: Baseline, PPE, Eng. Controls. Aerial applicators = Eng. Controls, all other estimates 

are baseline PPE.

2 Exposure Science Advisory Council Policy #9.1.

3 Inhalation Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (A or gal/day) ÷ BW (69 kg).

4 Inhalation MOE = Inhalation NOAEL (ST = 35 mg/kg/day) ÷ Inhalation Dose (mg/kg/day); LOC=100.

5 Orchard crops = Stone Fruits, Tree Nuts, and Ti Palm. The proposed application rate is the highest for Ti palm, so it has been used as a worst-case screen for this group. 

 
Azoxystrobin Human Health Risk Assessment DP Nos. D423691, D418374

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9.2 Short-/Intermediate-Term Post-Application Risk

9.2.1 Dermal Post-application Risk

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

potential for exposure following azoxystrobin application. However, an appropriate dermal 

endpoint was not identified for azoxystrobin. Therefore, an assessment of occupational dermal 

post-application exposure to azoxystrobin was not conducted. A chemical-specific 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. 

Restricted Entry Interval

Abound® Flowable Fungicide EPA Reg. No. 100-1098

Azoxystrobin is classified as Toxicity Category III based upon data for acute dermal toxicity, 

Toxicity Category III for acute inhalation toxicity, Toxicity Category IV for primary skin 

irritation, and Toxicity Category III for primary eye irritation. Typically, the REI specified on 

the proposed label is based on the acute toxicity of the active ingredient. Under 40 

CFR§156.208 (c) (2) (iii), active ingredients classified as Acute III or IV for acute dermal, eye 

irritation, and primary skin irritation are assigned a 12-hour REI. However, it is noted that the 

proposed product label has a 4-hr REI listed. REIs may be further reduced from 12 hours if 

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

accordance with the Pesticide Registration (PR) Notice 95-3 [Reduction of Worker Protection 

Standard (WPS) Interim Restricted Entry Intervals (REIs) for Certain Low Risk 

Pesticides]3. Based only on the acute toxicity categories, azoxystrobin is a possible candidate for 

a 4-hr REI, however, RD should ensure that the additional criteria listed in PR Notice 95-3 are 

met for the active ingredient and the end-use product.

9.2.2 Inhalation Post-application Risk

There are multiple potential sources of post-application inhalation exposure to individuals 

performing post-application activities in previously treated fields. These potential sources 

include volatilization of pesticides and resuspension of dusts and/or particulates that contain 

pesticides. The agency sought expert advice and input on issues related to volatilization of 

pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel 

(SAP) in December 2009, and received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The agency has 

evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent 

Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA-HQOPP-2014-0219). During Registration Review, the agency will utilize this analysis to determine 

if data (i.e., flux studies, route-specific inhalation toxicological studies) or further analysis is 

required for azoxystrobin.

In addition, the Agency is continuing to evaluate the available post-application inhalation 

exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the 

 

3 Available: http://www.epa.gov/PR_Notices/pr95-3.html
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Agency will continue to identify the need for and, subsequently, the way to incorporate 

occupational post-application inhalation exposure into the agency's risk assessments.

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

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

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

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

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

inhalation exposure scenarios.

The Worker Protection Standard for Agricultural Pesticides contains requirements for protecting 

workers from inhalation exposures during and after greenhouse applications through the use of 

ventilation requirements.[40 CFR 170.110, (3) (Restrictions associated with pesticide 

applications)]. 

It should be noted that there is the potential for inhalation exposure during the mechanical 

sweeping and windrowing of the tree nuts. However, since there is a long PHI of 45 days, the 

post-application inhalation exposure potential is negligible and was not quantitatively assessed.

Furthermore, inhalation exposure during dusty mechanical activities such as shaking and 

mechanical harvesting is another potential source of post-application inhalation 

exposure. However, the airblast applicator scenario is believed to represent a reasonable worst 

case surrogate estimate of post-application inhalation exposure during these dusty mechanical 

harvesting activities. The non-cancer inhalation risk estimate for commercial airblast application 

is not of concern (i.e., MOE > 100)

10.0 References

K. Rury. Azoxystrobin. Occupational and Residential Exposure Assessment for Proposed Uses 

on Ti Palm, and on Ornamentals and Vegetable Transplants Grown Outdoors and in 

Greenhouses. This assessment also includes updates to the Stone Fruit Group 12-12 and Tree 

Nut Group 14-12 Crop Groups. D418012 and D423961. 12/17/2014. 

K. Rury. Azoxystrobin. Human Health Risk Assessment for the Proposed Use on Sugarcane. 

D394285. 04/30/2012. 

M. Negussie. Azoxystrobin: Revised Human Health Risk Assessment for Use on Ginseng 

(Import), Rye, and Oats, and Section 3 Amendments to Revise the Established Tolerances on 

Cereal Grains (Barley and Wheat) Due to Changes of Pre-Harvest Intervals. D402285 and 

D402289. 03/21/2013. 

S. Funk. Azoxystrobin. Petition for the Establishment of Permanent Tolerances on Imported 

Pear, Imported Tea, and Imported Coffee. Petition for the Establishment of Permanent 

Tolerance on Ti Palm, and for Crop Group Conversions for Stone Fruit Group 12-12 and Tree 

Nut Group 14-12. Summary of Analytical Chemistry and Residue Data. D423334 and 

D423718. 11/12/2014. 
Azoxystrobin Human Health Risk Assessment DP Nos. D423691, D418374

Page 28 of 34

S. Funk. Azoxystrobin: Acute and Chronic Aggregate Dietary (Food and Drinking Water) 

Exposure and Risk Assessments for Section 3 Petitions for the Establishment of Tolerances on 

Coffee, Pear, and Tea (Import, PP#3E8228). Petition for the Establishment of Tolerances and 

Registration for Use on Ti Palm Roots and Leaves (PP#4E8319) and Crop Group Conversions 

for Stone Fruit Group 12-12 and Tree Nut Group 14-12. D423337 and D423720. 10/29/2014. 

I. Abdel-Saheb. Drinking Water Exposure Assessment for new use of Azoxystrobin on 

Ornamental Plants and Vegetable Transplants. D422726. 09/11/2014. 
Azoxystrobin Human Health Risk Assessment DP Nos. D423691, D418374

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Appendix A. Toxicology Profile 

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.500) for non-food use for azoxystrobin are below. 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

waived*

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

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

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

yes

yes

yes

yes

yes

yes

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

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

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

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

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

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

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

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

870.5375 Mutagenicity—Structural Chromosomal Aberrations...

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

yes

yes

yes

yes

yes

yes

yes

yes

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

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

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

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

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

no

no

yes

yes

no

-

-

yes

yes

no

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

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

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

yes

no

yes

yes

yes

waived**

Special Studies for Ocular Effects

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

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

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

yes

no

yes

-

-

-

1CR = Conditionally Required

* The requirement for a subchronic inhalation toxicity study has been waived (TXR#0056307)

** The requirement for an immunotoxicity study has been waived (TXR#0057071)
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A.2 Toxicity Profiles

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

Guideline

No. Study Type MRID # Results

Toxicity 

Category

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

Females

IV

870.1200 Acute Dermal -

Rat

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

Females

III

870.1300 Acute Inhalation -

Rat

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

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

The combined LC50 was not calculated

due to mortality pattern

III

870.2400 Primary Eye 

Irritation - Rabbit

43678128 Slight to moderate erythema and slight chemosis in 

all rabbits within one hour, but effects resolved 

within 48 hours of treatment.

III

870.2500 Primary Skin 

Irritation - Rabbit

43678130 Very slight erythema and edema that persisted for 

three days on one rabbit and for one hour on 

another.

IV

870.2600 Dermal 

Sensitization -

Guinea Pig

43678132 No erythema or edema were found 38 or 48 hrs 

after challenge with test material.

Not a 

dermal 

sensitizer

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

Study Guideline/Study MRID Results

870.3100

90-Day oral toxicity in rats

43678135 (1992) 

Acceptable/guideline

0, 200, 2000, 4000 ppm

M: 0, 20.4, 211.0, 443.8 

mg/kg/day

F: 0, 22.4, 223.0, 448.6 

mg/kg/day

NOAEL = 20 mg/kg/day

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

gain in both sexes, clinical observations of distended 

abdomens and reduced body size, and clinical 

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

Study Guideline/Study MRID Results

870.3800

Reproduction and fertility 

effects in rats

43678144 (1994)

Acceptable/guideline

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

Parental/Systemic NOAEL = 32 mg/kg/day

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

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 (for body 

weight) 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 43678147 (1992)

Acceptable/guideline

The in vitro test in human lymphocytes was positive

for the induction of chromosomal aberrations in both 
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Table A.2.2. Azoxystrobin Toxicity Results From Repeated Dosing and Other Studies.

Study Guideline/Study MRID Results

Cytogenetics chromosomal 

aberration 

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

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 and food utilization in both sexes.

870.7485

Metabolism and 

pharmacokinetics

43678150

43678151

43678152

43678153

43678154

1 or 100 mg/kg (single 

gavage) or 1 mg/kg (14-

day repeated)

Following oral administration as a single gavage 

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

mg/kg, azoxystrobin was widely distributed with the 

liver and kidneys having the highest concentrations; 

however, less than 0.5% of the administered dose 

was detected in the tissues at seven days postdosing. 

The primary route of excretion was via the feces

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

no apparent sex- or dose-related differences in 

distribution or in the pattern of excretion. In a bile 

duct cannulated single high-dose group, assessment 

of biliary excretion suggested approximately 70% 

absorption with ≈32% of the administered dose 

remaining as parent compound in the gastrointestinal 

tract. Absorbed azoxystrobin appeared to be 

extensively metabolized with minor sex-related 

qualitative and quantitative differences in biliary 

metabolites. A metabolic pathway was proposed 

showing hydrolysis and subsequent glucuronide 

conjugation as the major biotransformation process.

870.7600

Dermal penetration (rat)

43678155 (1994)

Acceptable/guideline

0.01, 0.1, 0.9, 13.3 mg/kg

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

Table B. Physicochemical Properties of Technical Grade Azoxystrobin.

Parameter Value Reference

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

3/19/96, J. Garbus pH 6.4

Density 1.25 g/cm3

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

pH 7.0 6.7 mg/L

pH 9.2 5.9 mg/L

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

Octanol 1.4 mg/L

Methanol 20 mg/L

Toluene 55 mg/L

Acetone 86 mg/L

Ethyl Acetate 130 mg/L

Acetonitrile 340 mg/L

Dichloromethane 400 mg/L

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

Dissociation constant, pKa Not dissociable

Octanol/water partition coefficient, 

Log(KOW)

log P = 2.5
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Appendix C. Review of Human Research

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

intentionally exposed to a pesticide or other chemical. These data, which include PHED 1.1; the 

AHETF database; the Residential SOPs (Residential Handlers), are (1) subject to ethics review 

pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable 

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

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

can be found at the Agency website4. 

 

4 http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

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