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7.4 Chronic Aggregate Risk .............................................................................................. 26

7.5 Cancer Aggregate Risk ................................................................................................ 26

8.0 Cumulative Exposure/Risk Characterization ............................................................... 26

9.0 Occupational Exposure/Risk Characterization ............................................................ 26

9.1 Short-/Intermediate-Term Handler Risk................................................................... 26

9.2 Short-/Intermediate-Term Post-Application Risk .................................................... 28

9.2.1 Dermal Post-Application Risk................................................................................. 28

10.0 References......................................................................................................................... 29

Appendix A. Toxicology Profile................................................................................................ 30

A.1 Toxicology Data Requirements................................................................................... 30

A.2 Toxicity Profiles............................................................................................................ 31

Appendix B. Physical/Chemical Properties............................................................................. 34

Appendix C. International Residue Limit Status Sheet. ........................................................ 35

Appendix D. Review of Human Research................................................................................ 36
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1.0 Executive Summary

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

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

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

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

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

transport. 

Syngenta Crop Protection, Inc. (Syngenta) has proposed azoxystrobin for use on sugarcane. The 

most recent human health risk assessment was conducted to evaluate azoxystrobin use on postharvest potatoes and to update the azoxystrobin use profile to include various crop group 

revisions (K. Rury, D389702, 01/18/2012). Since the last risk assessment, no additional hazard 

data have been submitted. In accordance with the 2007 revised 40 CFR Part 158 Toxicology 

data requirements, a subchronic inhalation toxicity study and an immunotoxicity study were 

required for azoxystrobin. The Agency has waived the inhalation toxicity study data requirement 

for azoxystrobin at this time (TXR# 0056307). An immunotoxicity study remains required for 

azoxystrobin. 

Use Profile

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

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

application rates on sugarcane range from 0.15-0.20 lb ai/A (or 9.0-12.0 fl oz product/A for 

Abound® Flowable Concentrate and 16-22 fl oz product/A for Quilt XcelTM). The Abound®

label specifies that no more than 0.80 lb ai/A of any azoxystrobin containing products should be 

applied per year; and no more than 4 foliar applications of Abound® should be applied per year. 

The Quilt XcelTM label specifies no more than 88 fl oz per acre per year (0.81 lb ai/A) should be 

applied. Both labels require a 45-day pre-harvest interval (PHI) for sugarcane used for animal 

feed, and a 30-day PHI for all other sugarcane treated with azoxystrobin. In addition, Syngenta

is requesting to add sugarcane use on two azoxystrobin manufacturing products: Azoxystrobin 

Millbase Manufacturing Use Product (MUP) (EPA Reg. No. 100-1220) and Azoxystrobin Dry 

Technical Manufacturing Use Concentrate (MUC) (EPA Reg. No. 100-1120). 

Toxicity/Hazard

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

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

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

(TXR# 0056307). In repeat-dose oral studies, the liver and bile ducts were consistently the 

target organs of azoxystrobin toxicity. No developmental effects were seen in rabbit or rat 

developmental toxicity studies and no reproductive or offspring effects were seen in the 2-

generation rat reproduction study. Although azoxystrobin induced a weak mutagenic response in 

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

whole animals (in vivo). Azoxystrobin is classified as ―not likely to be carcinogenic to humans.‖ 
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Azoxystrobin has a low order of acute toxicity via oral, dermal and inhalation routes of exposure 

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

and is not a skin sensitizer. 

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

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

assessing acute risk. No additional safety factor is needed for short-term, intermediate-term, and 

chronic risk assessment. Although an immunotoxicity study is needed to complete the 

toxicological database, there are no concerns for immunotoxicity based on the results of the 

existing studies. There are no indications in the available studies that organs associated with 

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

does not belong to a class of chemicals that would be expected to be immunotoxic. The selected 

toxicity endpoints and PODs for risk assessment are based on the most sensitive and relevant 

data. 

Dietary Exposure (Food and Water)

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

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

Azoxystrobin for use on sugarcane was incorporated into the previous drinking water assessment 

(R. Baris, D389703, 11/28/2011); therefore, estimated drinking water concentrations (EDWCs)

have not changed since the last risk assessment (K. Rury, D389702, 01/18/2012). The 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 (LOC) (<100% of the acute population 

adjusted dose (aPAD)) for all population subgroups and were estimated at 18% of the aPAD for 

the general U.S. 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 DEEM-FCIDTM 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 LOC (<100% of the 

chronic population adjusted dose (cPAD)) for all population subgroups and were estimated at 

6.7% of the cPAD for the general U.S. 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

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

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

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

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

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

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

and post-application activities. The results of the occupational handler exposure and risk 

assessment estimates indicate that total short- and intermediate-term MOEs are not of concern to 

HED (i.e. MOE > 100) with baseline attire. Although occupational dermal exposure is expected 

following treatment of sugarcane, no dermal hazard was identified for azoxystrobin. Therefore, 

a quantitative post-application dermal risk assessment was not conducted. HED assumes that

post-application inhalation exposures are minimal following applications of an active ingredient 

(ai) with low vapor pressure. Since azoxystrobin has low acute inhalation toxicity (Toxicity 

Category III) and a low vapor pressure, 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 data, including studies from the 

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

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

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

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

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

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

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

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

2.0 HED Recommendations

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

sugarcane. 

2.1 Data Deficiencies/Prior Conditions of Registration

The following data are required as a condition of registration: 

870.7800 Immunotoxicity Study

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

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

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

study would be completed in November 2011. The immunotoxicity study remains a 

condition of registration for azoxystrobin under Registration Review and is due in 2012.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method 
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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 no Canadian or Codex Maximum Residue Limits (MRLs) for residues of azoxystrobin 

and its Z-isomer for sugarcane. 

2.2.3 Recommended Tolerances 

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

preclude establishment of permanent tolerances for azoxystrobin in/on sugarcane. The tolerance 

value proposed by the petitioner for sugarcane is adequate and supported; HED recommends a 

tolerance of 0.2 ppm for sugarcane. The Organization for Economic Cooperation and 

Development (OECD) tolerance calculation procedures (March 2011 version) were utilized in 

determining the appropriate tolerance level. 

Table 2.2.3. Tolerance Summary for Azoxystrobin.

Commodity Established 

Tolerance (ppm)

Proposed 

Tolerance 

(ppm)

Recommended 

Tolerance (ppm)

Comments; Correct 

Commodity Definition

Sugarcane, cane N/A 0.2 0.2

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

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

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

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

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

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

2.2.4 Revisions to Petitioned-For Tolerances

There are no revisions to the petitioned-for tolerances. 

2.3 Label Recommendations

860.1200 Directions for Use

The following statement should be removed from the proposed supplemental labels (EPA 

Reg. Nos. 100-1098 and 100-1324): ―Do not apply within 45 days of harvest [45-day 

preharvest interval (PHI)] for animal feed.‖

The following statement should be removed from the proposed supplemental label for 

EPA Reg. No. 100-1098: ―An adjuvant may be used at recommended rates.‖ The 
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following statement should be added: ―A crop oil concentrate (COC) at 5% maximum

(v/v) or a non-ionic surfactant (NIS) at 1% maximum (v/v) may be added.‖

The following statement should be added to the proposed supplemental label for EPA 

Reg. No.100-1324 for use on sugarcane: ―A crop oil concentrate (COC) at 5% maximum 

(v/v) or a non-ionic surfactant (NIS) at 1% maximum (v/v) may be added.‖

The rotational crop restrictions on the registered label for Quilt Xcel® Fungicide (EPA 

Reg. No. 100-1324) should be revised to increase the plant-back interval (PBI) for carrot 

from 0 days to 36 days.

3.0 Introduction

Azoxystrobin is a broad spectrum fungicide used to 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 naturally occurring strobilurins and is structurally related. Azoxystrobin is a -

methoxyacrylate, and acts by inhibiting electron transport. 

Syngenta has requested azoxystrobin be registered for use on sugarcane. 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) (EPA Reg. No. 100-1098) and Quilt 

XcelTM (13.5% ai) (EPA Reg. No. 100-1324). Quilt XcelTM is a multiple active ingredient (MAI) 

product formulation containing both azoxystrobin and propiconazole (11.7%). Propiconazole 

use on sugarcane has been previously assessed (M. Dow, D337829, 04/10/2007). In addition, 

Syngenta is requesting to add sugarcane use on two azoxystrobin manufacturing products: 

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

Azoxystrobin Dry Technical Manufacturing Use Concentrate (MUC) (EPA Reg. No. 100-1120). 

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

chemigation equipment. Proposed single application rates on sugarcane range from 0.15-0.20 lb 

ai/A (or 9-12 fl oz product/A for Abound® and 16-22 fl oz product/A for Quilt XcelTM). The 

Abound® label specifies that no more than 0.80 lb ai/A of any azoxystrobin containing products 

should be applied per year, and no more than 4 foliar applications of Abound® should be applied 

per year. The Quilt XcelTM label specifies no more than 88 fl oz per acre per year (0.81 lb ai/A) 

should be applied. 

3.1 Chemical Identity

The chemical structure and nomenclature of azoxystrobin are presented in Table 3.1.
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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. 100-1098);

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 and is considered 

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

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

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

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

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

physicochemical properties of azoxystrobin are summarized in Appendix B. 

3.3 Pesticide Use Pattern

Syngenta submitted two draft supplemental amended labels adding use on sugarcane for 

Abound® Flowable Fungicide (EPA Reg. No. 100-1098) and Quilt XcelTM (EPA Reg. No. 100-

1324). In addition, Syngenta is requesting to add sugarcane use on two azoxystrobin 

manufacturing products: Azoxystrobin Millbase Manufacturing Use Product (MUP) (EPA Reg. 

N N

O O

CN OCH3

O

H3CO

N N

O O

CN

O OCH3

H3CO
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No. 100-1220) and Azoxystrobin Dry Technical Manufacturing Use Concentrate (MUC) (EPA 

Reg. No. 100-1120). Table 3.3 provides a summary of the proposed use sites of azoxystrobin. 

Table 3.3. Proposed Uses of Azoxystrobin

Product

(EPA 

Registration 

No.)

Use Site Application 

Method

Single 

Application 

Rate Range 

Maximum 

Seasonal 

Application 

Rate 

(lb ai/A)

Comments

Abound®

(100-1098)

22.9%

2.08 lb ai/gal

Sugarcane

Apply 

Liquid via 

Ground, 

Aerial, or 

Chemigation

9-12 fl oz

product/A

0.15-0.20 lb 

ai/A

0.8

Do not apply more than 0.80 lb ai/A of any 

azoxystrobin containing product per season. 

Abound® applications should begin prior to 

rust development and continue throughout 

the season every 14-28 days following 

resistance management guidelines. Do not 

make more than 2 sequential foliar 

applications of Abound® or other Group 11 

fungicide before alternation with another 

fungicide not in Group 11. Do not make 

more than 4 applications of Abound® or 

other Group 11 fungicides per acre per year. 

The label requires a 45-day pre-harvest 

interval (PHI) for sugarcane used for animal 

feed, and a 30-day PHI for all other 

sugarcane treated with azoxystrobin.

Quilt XcelTM 

(100-1324)

13.5%

1.18 lb ai/gal

16-22 fl oz

product/A

0.15-0.20 lb 

ai/A

Do not apply more than 88 fl oz/A (0.8 lb 

ai/A) of Quilt XcelTM per year. Applications 

should begin prior to rust developmental and 

continue throughout the season every 14-28 

days following resistance management 

guidelines. The label requires a 45-day preharvest interval (PHI) for sugarcane used for 

animal feed, and a 30-day PHI for all other 

sugarcane treated with azoxystrobin.

3.4 Anticipated Exposure Pathways

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

proposed new use of azoxystrobin on sugarcane. 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 
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uses of azoxystrobin, but also considers existing uses of azoxystrobin, particularly in the dietary 

exposure assessment. 

3.5 Consideration of Environmental Justice

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

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

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

(http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. As a part of every pesticide risk 

assessment, OPP considers a large variety of consumer subgroups according to well-established 

procedures. In line with OPP policy, HED estimates risks to population subgroups from 

pesticide exposures that are based on patterns of that subgroup’s food and water consumption, 

and activities in and around the home that involve pesticide use in a residential setting. 

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

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

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

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

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

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

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

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

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

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

submitted to the Agency in 2012. 

4.1 Toxicological Effects

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. Dietary administration of azoxystrobin 

to rats resulted in decreased body weights, decreased food intake and utilization, increased 

diarrhea, and other clinical toxicity observations (increased urinary incontinence, hunched 

postures, and distended abdomens). In addition, liver effects, characterized by increased liver 
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weights, increases in alkaline phosphatase and gama glutamyltransferase, decreases in albumin,

and gross and histological lesions in the liver and bile ducts, were seen in rats. In dogs, effects 

on liver/biliary function were found after oral administration. 

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

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

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

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

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

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

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

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

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

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

azoxystrobin as ―not likely to be carcinogenic to humans.‖ Azoxystrobin induced a weak 

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

expected to be expressed in whole animals.

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

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

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

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

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

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

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

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

based on the following considerations:

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

insignificant 

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

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

gavage dosing in rabbits; and 

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

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

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

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

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

4.2.1 Completeness of the Toxicology Database

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

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

Guideline 870.7800) required for pesticide registration; however, the existing data are sufficient 
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for endpoint selection for exposure/risk assessment scenarios, and for evaluation of the 

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

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

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

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

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

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

not need to be applied. 

A subchronic inhalation toxicity study is not required for azoxystrobin at this time (TXR# 

0056307). 

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 is no need for a developmental neurotoxicity study 

or additional UFs to account for neurotoxicity.

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

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

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

study. 

4.2.4 Residual Uncertainty in the Exposure Database

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

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

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

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

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

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

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

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

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

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

drinking water assessment utilized water concentration values generated by models and 

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

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

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

infants, children, or women of child bearing age. 

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

employing surrogate study data, including conservative exposure assumptions based on Day 0 
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dermal/oral contact to turf and surfaces treated at the maximum application rate. These data are 

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

are based upon reasonable ―worst-case‖ assumptions are not expected to underestimate risk. 

4.3 Toxicity Endpoint and Point of Departure Selections

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

Risk Assessment 

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

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

toxicity endpoints and PODs are presented in Table 4.3.1.

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

1

Exposure/

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, Level of 

Concern for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary

(All 

Populations)

LOAEL = 200

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 

3X

Acute RfD = 

0.67mg/kg/day

aPAD = 0.67

mg/kg/day

Acute Neurotoxicity - Rat. LOAEL 

= 200 mg/kg/day based on diarrhea at 

two-hours post dose at all dose levels 

including the LOAEL.

Chronic 

Dietary (All 

Populations)

NOAEL = 18

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 

1X

Chronic RfD = 0.18 

mg/kg/day

cPAD = 0.18

mg/kg/day

Combined Chronic 

Toxicity/Carcinogenicity Feeding 

Study – Rat. LOAEL = 82.4/117 

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

body weights in both sexes and bile 

duct lesions in males.

Incidental 

Oral ShortTerm (1-30 

days)

NOAEL = 25

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 

1X

Residential LOC for 

MOE = 100

Prenatal Developmental Oral 

Toxicity – Rat. LOAEL = 100 

mg/kg/day based on increased 

maternal diarrhea, urinary 

incontinence, and salivation.

Incidental 

Oral 

IntermediateTerm (1-6 

months)

NOAEL = 20

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 

1X

Residential LOC for 

MOE = 100

90-day Feeding Study – Rat. 

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

based on decreased body weight gain 

in both sexes and clinical signs 

indicative of reduced nutrition.

Dermal 

(All 

Durations)

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

– Rat. No dermal or systemic 

toxicity was seen at the limit dose 

(1,000 mg/kg/day).

Inhalation 

Short-Term 

(1-30 days)

Oral NOAEL 

= 25

UFA = 10X

UFH = 10X

FQPA SF = 

1X

Occupational & 

Residential LOC for 

MOE = 100

Prenatal Developmental Oral 

Toxicity – Rat. LOAEL = 100 

mg/kg/day based on increased 

maternal diarrhea, urinary 

incontinence, and salivation.

Inhalation 

IntermediateTerm 

(1-6 months)

Oral NOAEL 

= 20

UFA = 10X

UFH = 10X

FQPA SF=1X

Occupational & 

Residential LOC for 

MOE = 100

90-day Feeding Study – Rat. 

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

based on decreased body weight gain 

in both sexes and clinical signs 

indicative of reduced nutrition.
Azoxystrobin Human Health Risk Assessment DP No. 394285

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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.

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

risk for azoxystrobin was assessed using an oral toxicity study. The Agency sought expert 

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

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

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

SAP’s final report on March 2, 2010 

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

process of evaluating the SAP report and may, as appropriate, re-examine and develop new 

policies and procedures for conducting inhalation risk assessments, including route to route 

extrapolation of toxicity data. If any new policies or procedures are developed, the Agency may 

revisit the need for an inhalation toxicity study for azoxystrobin and/or re-examine the inhalation 

toxicity risk assessment.

5.0 Dietary Exposure and Risk Assessment 

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 (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, DP#390838, 

11/29/2011. 

- Azoxystrobin: Section 3 Petition for Uses On Tuberous and Corm Vegetables Subgroup 1C (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, 01/04/2012. 

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

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

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

Subgroups A, B, C; and Citrus Fruit Group 10-10). K. Rury, DP# 389702, 01/18/2012. 
Azoxystrobin Human Health Risk Assessment DP No. 394285

Page 16 of 36

- 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, 11/28/2011.

- Azoxystrobin. Petition for Registration of Use on Sugarcane (PP#1F7891). Summary of Analytical and 

Chemistry and Residue Data, M. Negussie, DP#393151, DP#393155, DP#393156, DP#393157, 03/14/2012. 

- 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, 01/16/2010. 

5.1 Metabolite/Degradate Residue Profile

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

Pathway Comparison

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

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

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

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

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

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

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

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

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

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

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

5.1.2 Residues of Concern Summary 

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

Tolerance Expression.

Matrix

Residues included in

Risk Assessment

Residues included in

Tolerance Expression

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

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

Livestock Ruminant Azoxystrobin Azoxystrobin

Poultry Azoxystrobin Azoxystrobin

Drinking Water Azoxystrobin Not Applicable

5.2 Food Residue Profile
Azoxystrobin Human Health Risk Assessment DP No. 394285

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

tolerances of azoxystrobin on sugarcane. 

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 commodities under frozen conditions. 

Proposed Uses 

Other than the sugarcane field trial data (MRID 48496901), no new residue field trial data were 

submitted to support the proposed tolerances. Six field trials were conducted in the United States 

during the 2008-2009 growing season. Although geographic representation is technically 

inadequate, HED concludes that the available data are sufficient to support registration of 

azoxystrobin on sugarcane because trials were conducted in zones representing 100% of 

sugarcane production in the U.S., and there is not a great deal of variability in the residue values 

across the trial sites. A summary of the residue data from the sugarcane field trials is provided in 

Table 5.2.a.

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

Commodity Analyte Total App. 

Rate 

(lb ai/A) 

PHI Residue Levels (ppm)1

n Sample 

Min.

Sample 

Max.

LAFT2 HAFT2 Median Mean Std. 

Dev.

Sugarcane (proposed use = 0.15-0.20 lb ai/A total application rate, 30-day PHI & 45-day PHI for animal feed)

Sugarcane Azoxystrobin 0.761-0.802 27-30 6 <0.01 0.111 0.029 0.089 0.049 0.053 0.024

R230310 6 <0.01 <0.01 0.01 0.01 0.01 0.01 N/A

Total Residues 6 <0.02 <0.121 0.039 0.099 0.059 0.063 0.024

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

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

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

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

residues of azoxystrobin, Z-isomer (R230310), and total residues (azoxystrobin and Z-isomer) 

did not concentrate in molasses or refined sugar. All of the processing factors calculated in this 

study were less than the maximum theoretical concentration factors for sugarcane (11.8x for 

sugar and 20x for molasses). 

Acceptable methods were used for the determination of residues of azoxystrobin and the Zisomer metabolite. The sample storage conditions and durations for azoxystrobin analyses are 

supported by adequate storage stability data. Results of the sugarcane processing study are 

provided in Table 5.2b. 
Azoxystrobin Human Health Risk Assessment DP No. 394285

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1The LOQ = 0.01 ppm. Per trial averages are calculated using the LOQ for all residues reported as <LOQ.

2

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

Livestock

The only livestock feedstuff associated with this petition is sugarcane molasses; this commodity 

is fed to beef and dairy cattle but is not fed to poultry or swine. The dietary burdens of 

azoxystrobin to livestock, based on reasonably balance diets, were calculated most recently in 

D390152 (M. Negussie, 01/04/2012). Dietary burdens were 51.3 and 40.4 ppm for beef and 

dairy cattle, respectively, and 14.4 and 15.0 ppm for poultry and swine, respectively. Dietary 

burdens were calculated based on tolerances of cereal grain, non-grass animal feeds, canola, 

cotton, and soybean commodities. The addition of sugarcane to the dietary burden calculation 

would not be expected to alter the dietary exposure of ruminants to azoxystrobin. Sugarcane 

molasses contributes no more than 0.03 ppm azoxystrobin to the dietary burden, about 0.1% of 

the existing burden. 

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

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

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

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

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

for poultry tissues or eggs. 

Rotational Crops

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

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

sugarcane does not result in increased maximum seasonal application rates of azoxystrobin, no 

changes to the existing rotational crop restrictions are needed. However, revisions to the 

rotational crop restrictions are recommended for EPA Reg. No. 100-1324; the label should be 

revised to increase the PBI for carrot from 0 days to 36 days. 

5.3 Water Residue Profile

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

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

wasabi, dragon-fruit and sugarcane (R. Baris, D389703/394475, 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 use, has the highest application rate (0.55 lb ai/A, 9 applications per year with a 10-

day interval between applications). The assessment was completed with the Tier 1 screening 

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

RAC Processed 

Commodity

Total Rate

(lb ai/A) PHI Average of Total (Azoxystrobin and Z-isomer) Residues (ppm)1 Processing Factor2

Sugarcane Cane

(RAC)

3.93-3.94 27-30

0.420 --

Molasses 0.218 0.52x

Refined 

Sugar <0.02 <0.05x
Azoxystrobin Human Health Risk Assessment DP No. 394285

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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/.

The proposed rates of application for sugarcane are lower than for turf. Therefore, the EDWCs 

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

for all proposed/registered crops are listed in Table 5.2. For ground water, the estimated 

drinking water concentration is 3.1 ppb. 

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. 

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

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

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

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

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

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

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

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

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

5.4.2 Acute Dietary Risk Assessment

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

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

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

water utilized 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 
Azoxystrobin Human Health Risk Assessment DP No. 394285

Page 20 of 36

42% of the aPAD. The results are reported in Table 5.4.4. All population subgroups were below 

the LOC. 

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

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

residue trials [Grapefruit = 5.447 ppm, Orange = 4.014 ppm, Orange, peel = 5.538 ppm, Lemon 

= 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 

reported exposed population subgroup, children 1-2 years old, utilized 16% of the cPAD. The 

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

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

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

information for the crops listed in Section 5.4.1. 

5.4.4 Summary Table

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

Population Subgroup

Acute Dietary 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 18 0.012050 6.7

N/A N/A

All Infants (< 1 year old) 0.146102 22 0.015196 8.4

Children 1-2 years old 0.279450 42 0.027847 16

Children 3-5 years old 0.218767 33 0.024065 13

Children 6-12 years old 0.144459 22 0.015268 8.5

Youth 13-19 years old 0.115468 17 0.011208 6.2

Adults 20-49 years old 0.100143 15 0.010190 5.7

Adults 50+ years old 0.094256 14 0.010004 5.6

Females 13-49 years old 0.102333 15 0.009822 5.5

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

References: 
Azoxystrobin Human Health Risk Assessment DP No. 394285

Page 21 of 36

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

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

This document addresses the proposed new agricultural use of azoxystrobin on sugarcane; 

therefore, no new residential exposure is expected. However, there are currently registered uses 

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

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

residential use patterns has previously been assessed by HED and the resulting exposures and 

risk estimates do not exceed HED’s LOC. However, HED has recently updated the residential 

standard operating procedures (SOPs) and body weights to be used in all human health 

assessments. Therefore, all the existing residential use patterns have been reassessed for 

residential handler and post-application exposures using these new procedures and data (K. Rury, 

D394287, 03/30/2012). 

6.1 Residential Handler Exposure

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

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

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

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

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

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

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

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

body weight assumptions. It is assumed that most residential 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. Because there was no dermal 

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

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

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

adult handlers. 

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

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

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

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

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

Table 6.1 lists the updated assessments of residential handler exposures and risk estimates using 

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

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

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

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

gardens and trees using a hose-end sprayer). 
Azoxystrobin Human Health Risk Assessment DP No. 394285

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Table 6.1. Residential Handler Summary of Registered Azoxystrobin Use Sites

Activity Application 

Rate

Area 

Treated/Amount 

Applied 

(per day)

Inhalation 

UE 

(mg/lb ai)1

Short-Term 

Inhalation 

Dose2

(mg/kg/day)

Short-Term 

Inhalation 

MOE3

Painting with Airless Sprayer 1.0% ai by 

weight 15 one-gallon cans 0.56 0.0149 2,400

Painting with a Brush 1.0% ai by 

weight 2 one-gallon cans 0.2 0.0005 50,000

Indoor Manually-Pressurized Handwand 

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

Indoor Manually-Pressurized Handwand 

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

M/L/A Wettable Powders to Turf [Hose 

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

M/L/A Wettable Powder to Turf 

[Manually Pressurized Handwand or 

Backpack Sprayer]

0.011 (lb ai/gal) 5 gallons 1.1 0.00076 33,000

M/L/A Wettable Powders in WSB to 

Turf [Hose End Sprayer] 0.95 (lb ai/A) 0.5 acres 0.034 0.0002 120,000

M/L/A Wettable Powder in WSB to Turf 

[Manually Pressurized Handwand or 

Backpack Sprayer]

0.011 (lb ai/gal) 5 gallons 0.018 0.000012 2,000,000

M/L/A Wettable Powder Azoxystrobin to 

Gardens and Trees [ManuallyPressurized Handwand or Backpack 

Sprayer]

0.000125 (lb 

ai/gal) 5 gallons 1.1 0.0000086 2,900,000

M/L/A Wettable Powder Azoxystrobin to 

Gardens and Trees [Hose-End Sprayer]

0.000125 (lb 

ai/gal) 11 gallons 0.0014 0.000000024 1,000,000,000

M/L/A Wettable Powder Water Soluble 

Packets Azoxystrobin to Gardens and 

Trees [Manually-Pressurized Handwand 

or Backpack Sprayer]

0.000125 (lb 

ai/gal) 5 gallons 0.018 0.00000014 180,000,000

M/L/A Wettable Powder Water Soluble 

Packets Azoxystrobin to Gardens and 

Trees [Hose-End Sprayer]

0.000125 (lb 

ai/gal) 11 gallons 0.034 0.00000059 43,000,000

1. Inhalation Unit Exposures taken from the 2012 Residential SOPs

2. Inhalation Dose = (Daily Unit Exposure (mg/lb ai) x application rate x area treated daily or amount applied per day)/body weight (80 kg)

3. Inhalation MOE = NOAEL (25 mg/kg/day for short-term exposures)/Daily Dose (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. No 

dermal endpoint was chosen for azoxystrobin; therefore, a dermal post-application risk 

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

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

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

duration only. Tables 6.2a and 6.2b lists the updated assessments of residential post-application 

exposures and risk estimates. The MOEs ranged from 250 to 810,000 for incidental oral 

ingestion. The MOE for adults was 220,000,000 and was 52,000,000,000 for children for indoor 

post-application inhalation exposure. The new exposure and risk estimates for all residential 
Azoxystrobin Human Health Risk Assessment DP No. 394285

Page 23 of 36

post-application uses result in risk estimates that are greater than the LOC MOE of 100, and 

therefore are not of concern to HED. 

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

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

0056307). 

Table 6.2a. Exposure and Risk from Post-Application Exposure to Azoxystrobin - Children

Scenarios Short-Term Dose 

(mg/kg/day)1 Short-Term MOE2

Post-Application Inhalation (Indoor) 0.00000000087 52,000,000,000

Incidental Oral Indoor Scenarios

Hand-to-Mouth (vinyl/hard surfaces) 0.0327 760

Hand-to-Mouth (carpet/textile surfaces) 0.0982 250

Object-to-Mouth (vinyl/hard surfaces) 0.0087 2900

Object-to-Mouth (carpet/hard surfaces) 0.013 1900

Incidental Oral Treated Turf Scenarios

Hand-to-Mouth Liquid 0.0142 1,800

Object-to-Mouth Liquid 0.00043 57,000

Soil Ingestion (Liquid) 0.000031 810,000

Hand-to-Mouth Granular 0.0142 18,000

Object-to-Mouth Granular 0.000087 290,000

Soil Ingestion (Granular) 0.000031 810,000

Granular Ingestion 0.082 2,500

1. Inhalation Dose = ((((Inhalation Rate (m3/hr) (0.64 for adults, 0.33 children)* mass of ai (mg))/(ACH (0.45 (1/hr))*Vol of room (33 

m

3

))*(1-(((ACH (0.45 (1/hr))*EXP(-(1.4E-11(1/hr)*ET (18 hrs children))))-(1.4E-11(1/hr)*EXP(-(ACH*ET (hrs)))))/(ACH (0.45)-

1.4E-11 (1/hr)))))*Inhalation Absorption/Inhalation POD)

Hand-to-Mouth Dose = [(Hand residue loading (mg/cm2) x Fraction of hand mouthed (0.13) x surface area of 1 hand (150 cm2) x 

Exposure Time (1.5 hrs/day) x #Replenishment intervals/hr (4) x (1-((1-Fraction Saliva Extraction (0.48))^(Number of hand-tomouth events per hour (events/hr)/Number of replenishment intervals/hr (4))]/ body weight (11 kg)

Object-to-Mouth Dose = ((Object Residue (μg/cm2)*CF1 (1.0E-3 mg/μg)*Object Surface Area Mouthed/Event (10 

cm2/event))*(Exposure Time (1.5 hrs/day)*#Replenishment intervals/hr (4))*(1-((1-Extraction by Saliva (0.48))^(#Object-to-Mouth 

Events/hr (8.8 events/hr)/#Replenishment intervals/hr))))/Body Weight (11kg)

Soil Ingestion = (Soil Residue (7.0746975 μg/g) *Ingestion Rate (50 mg/day)*Conversion Factor (0.000001))/body weight (11 kg)

Granule Ingestion = ((% ai in the product)*Ingestion Rate (0.3 g/day)*Conversion Factor (1000))/body weight (11 kg)

2. MOE = NOAEL/LOAEL/Daily Dose (mg ai/kg/day); Inhalation NOAEL = 25 mg/kg/day, Acute oral NOAEL (for assessing 

granular ingestion) = 200 mg/kg/day. 

Table 6.2b. Exposure and Risk from Post-Application Exposure to Azoxystrobin - Adults

Scenarios Short-Term Dose1

(mg/kg/day) Short-Term MOE2

Post-Application Inhalation (Indoor) 0.00000000011 220,000,000,000

1. Inhalation Dose = ((((Inhalation Rate (m3/hr) (0.64 for adults, 0.33 children)* mass of ai (mg))/(ACH (0.45 (1/hr))*Vol of room (33 

m

3

))*(1-(((ACH (0.45 (1/hr))*EXP(-(1.4E-11(1/hr)*ET (16 hrs adults))))-(1.4E-11(1/hr)*EXP(-(ACH*ET (hrs)))))/(ACH (0.45)-

1.4E-11 (1/hr)))))*Inhalation Absorption/Inhalation POD)

2. MOE = NOAEL (25 mg/kg/day for short-term exposures)/Daily Dose (mg ai/kg/day)

6.3 Combined Exposure

FQPA requires residential exposures that could reasonably be expected to occur on the same day 
Azoxystrobin Human Health Risk Assessment DP No. 394285

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

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

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

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

azoxystrobin were not combined. 

6.4 Residential Bystander Post-Application Inhalation Exposure

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

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

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

protective of most post-application inhalation exposure scenarios.

6.5 Spray Drift

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

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

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

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

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

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

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

Agency is now requiring interim mitigation measures for aerial applications that must be placed 

on product labels/labeling. The Agency has completed its evaluation of the new database 

submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is 

developing a policy on how to appropriately apply the data and the AgDRIFT computer model to 

its risk assessments for pesticides applied by air, orchard airblast and ground hydraulic methods. 

After the policy is in place, the Agency may impose further refinements in spray drift 

management practices to reduce off-target drift with specific products with significant risks 

associated with drift.

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risks from three major sources: food, drinking water and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (e.g. a NOAEL or PAD), or the risks themselves can be aggregated. When 

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

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

residential scenarios were aggregated. 

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

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

concern resulting from sugarcane use, nor from utilizing the new Residential SOPs to estimate 

residential exposure and risk.
Azoxystrobin Human Health Risk Assessment DP No. 394285

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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 18% of the aPAD for the general U.S. population, and 42% for the 

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

7.2 Short-Term Aggregate Risk

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

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

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

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

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

The adult (inhalation) aggregate MOE (for adult males) is 460, and the adult (inhalation) 

aggregate MOE for females 13-49 years was 470. 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 200, 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-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 0.012 0.042 0.054 460

Females 13-49

years

25 100 1 0.011 0.042 0.089 470

Children 1-2

years

25 100 1 0.028 0.098 0.13 200

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

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

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

6.1 and Table 6.2a). Exposure estimate for Children 1-2 years includes post-application inhalation exposure (0.00000000087 mg/kg/day)+ 

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

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

5. Aggregate MOE = [NOAEL , 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. In the previous risk assessment, both short- and intermediate-term 

incidental-oral residential risks were included in the aggregate risk assessment for azoxystrobin
Azoxystrobin Human Health Risk Assessment DP No. 394285

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

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

should be included in the aggregate risk assessment. 

7.4 Chronic Aggregate Risk

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

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

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

exposure assessment. 

7.5 Cancer Aggregate Risk

Azoxystrobin is considered ―not likely to be carcinogenic to humans;‖ therefore, an aggregate 

cancer risk assessment has not been conducted. 

8.0 Cumulative Exposure/Risk Characterization

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

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

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

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

EPA has not assumed that azoxystrobin has a common mechanism of toxicity with other 

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

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

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

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

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

9.0 Occupational Exposure/Risk Characterization

References:

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

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

9.1 Short-/Intermediate-Term Handler Risk

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

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

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

exposure during handling (mixing, loading, and applying) 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 chemicalresistant gloves, and no respirator). Both the Quilt XcelTM and Abound® require handlers to 

wear long sleeved shirts, long pants, chemical resistant gloves, shoes, and socks. Quilt XcelTM 

also requires the use of protective eyewear. 
Azoxystrobin Human Health Risk Assessment DP No. 394285

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Sugarcane farms are typically large in scale; the share of sugarcane production in the US of 

farms larger than 2,000 acres is disproportionately high1,2. Therefore, based on HED ExpoSAC 

Policy No. 9.1 and information gathered on typical sugarcane farm size, sugarcane was treated as 

a ―high acreage crop.‖ 

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

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

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

risk assessment for azoxystrobin is 100X for 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 sugarcane 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 

intermediate-term MOEs are not of concern to HED (i.e. an MOE > 100) with baseline attire. 

The short-term inhalation MOEs range from 38,000 to 230,000 for occupational application of 

azoxystrobin to sugarcane. The intermediate-term MOEs range from 30,000 to 180,000 for 

occupational application of azoxystrobin to sugarcane. 

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

Estimates for Azoxystrobin on Sugarcane 

Scenario 

Maximum Single 

Application Rate 

(lb ai/A)1

Acres 

Treated 

per Day2

Inhalation 

Baseline Unit 

Exposure 

(mg/lb ai)3

Inhalation 

Daily Dose4

(mg/kg/day)

Baseline 

Inhalation 

MOE5

Short-Term Occupational Handler

M/L for Aerial Applications 0.2 1200 0.000219 0.000657 38,000

M/L for Groundboom Applications 0.2 200 0.000219 0.0001095 230,000

M/L for Chemigation Applications 0.2 350 0.000219 0.000191625 130,000

Aerial Application 0.2 1200 0.000068 0.000204 120,000

Groundboom Application 0.2 200 0.00034 0.00017 150,000

Flagger 0.2 350 0.00035 0.00030625 82,000

Intermediate-Term Occupational Handler

M/L for Aerial Applications 0.2 1200 0.000219 0.000657 30,000

M/L for Groundboom Applications 0.2 200 0.000219 0.0001095 180,000

M/L for Chemigation Applications 0.2 350 0.000219 0.000191625 100,000

Aerial Application 0.2 1200 0.000068 0.000204 98,000

Groundboom Application 0.2 200 0.00034 0.00017 120,000

Flagger 0.2 350 0.00035 0.00030625 65,000

 

1

http://www.sweetenerusers.org/sugarstructure.pdf

2

http://www.ipmcenters.org/cropprofiles/docs/FLsugarcane.pdf
Azoxystrobin Human Health Risk Assessment DP No. 394285

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

Estimates for Azoxystrobin on Sugarcane 

Scenario 

Maximum Single 

Application Rate 

(lb ai/A)1

Acres 

Treated 

per Day2

Inhalation 

Baseline Unit 

Exposure 

(mg/lb ai)3

Inhalation 

Daily Dose4

(mg/kg/day)

Baseline 

Inhalation 

MOE5

1. Application Rates based on the proposed labels Abound® Flowable Fungicide (EPA Reg. No. 100-1098) and Quilt Xcel® 

Fungicide (EPA Reg. No. 100-1324).

2. Acres Treated based on ExpoSAC Policy #9 - Standard Values for Daily Acres Treated in Agriculture (7/5/2000) and information 

gathered on sugarcane production in the US. 

3. Unit Exposures based on the Occupational Pesticide Handler Unit Exposure Surrogate Reference Table (9/26/2011) available at: 

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

4. Inhalation Dose = (Daily unit exposure (mg/lb ai) * application rate (lb ai/A) * acres treated daily) / body weight (80kg).

5. Inhalation MOE = NOAEL (25 mg/kg/day for short-term exposures, 20 mg/kg/day for intermediate-term exposures)/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 application 

to sugarcane, resulting in the potential for exposure to azoxystrobin during scouting, hand 

weeding, and possibly hand harvesting. However, no appropriate dermal endpoint was identified 

for azoxystrobin. Therefore, an assessment of occupational dermal post-application exposure to 

azoxystrobin was not conducted. A chemical-specific dislodgeable foliar residue (DFR) study is 

available for the use of azoxystrobin 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. However, 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 is in the 

process of evaluating the SAP report as well as available post-application inhalation exposure 

data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies 

and procedures, to identify the need for and, subsequently, the way to incorporate occupational 

post-application inhalation exposure into the Agency's risk assessments. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for azoxystrobin.

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

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

handlers. Handler exposure resulting from mixing/loading pesticides after harvest is likely to 

result in higher exposure than post-application exposure. Therefore, it is expected that these 
Azoxystrobin Human Health Risk Assessment DP No. 394285

Page 29 of 36

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 usually is the shortest 

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

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

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

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

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

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

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

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

propiconazole, is acceptable under the WPS. 

10.0 References

R. Baris, 11/28/2011, 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, 11/29/2011, 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, 03/14/2012, DP#393151, DP#393155, DP#393156, DP#393157, Azoxystrobin: 

Petition for Registration of Use on Sugarcane (PP#1F7891). Summary of Analytical Chemistry 

and Residue Data. 

K. Rury, 03/30/2012, DP#394287, Azoxystrobin. Occupational and Residential Exposure 

Assessment to Evaluate the Risk from Proposed Use on Sugarcane.

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

fungicide (EPA Reg. No. 100-1313) Azoxystrobin for use on golf course turf (only). 
Azoxystrobin Human Health Risk Assessment DP No. 394285

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Appendix A. Toxicology Profile 

A.1 Toxicology Data Requirements

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

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

Study

Technical

Required Satisfied

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

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

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

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

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

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

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

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

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

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

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

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

yes

yes

yes

no

CR1

yes

yes

yes

no

yes*

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

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

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

yes

yes

yes

yes

yes

yes

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

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

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

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

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

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

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

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

870.5375 Mutagenicity—Structural Chromosomal Aberrations...

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

yes

yes

yes

yes

yes

yes

yes

yes

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

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

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

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

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

no

no

yes

yes

no

-

-

yes

yes

no

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

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

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

yes

no

yes

yes

yes

no

Special Studies for Ocular Effects

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

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

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

yes

no

yes

-

-

-

1CR = Conditionally Required

* The requirement for a subchronic inhalation toxicity study has been waived (TXR#0056307)
Azoxystrobin Human Health Risk Assessment DP No. 394285

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A.2 Toxicity Profiles

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

Guideline

No. Study Type MRID # Results

Toxicity 

Category

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

Females

IV

870.1200 Acute Dermal -

Rat

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

Females

III

870.1300 Acute Inhalation -

Rat

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

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

The combined LC50 was not calculated

due to mortality pattern

III

870.2400 Primary Eye 

Irritation - Rabbit

43678128 Slight to moderate erythema and slight chemosis in 

all rabbits within one hour, but effects resolved 

within 48 hours of treatment.

III

870.2500 Primary Skin 

Irritation - Rabbit

43678130 Very slight erythema and edema that persisted for 

three days on one rabbit and for one hour on 

another.

IV

870.2600 Dermal 

Sensitization -

Guinea Pig

43678132 No erythema or edema were found 38 or 48 hrs 

after challenge with test material.

Not a 

dermal 

sensitizer

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

Study Guideline/Study MRID Results

870.3100

90-Day oral toxicity in 

rats

43678135 (1992) 

Acceptable/guideline

0, 200, 2000, 4000 ppm

M: 0, 20.4, 211.0, 443.8 

mg/kg/day

F: 0, 22.4, 223.0, 448.6 

mg/kg/day

NOAEL = 20 mg/kg/day

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

gain in both sexes, clinical observations of distended 

abdomens and reduced body size, and clinical 

pathology findings attributable to reduced nutritional 

status.

870.3150

90-Day oral toxicity in 

dogs

43678136 (1993)

Acceptable/guideline

M & F: 0, 10, 50, 250 

mg/kg/day 

NOAEL = 50 mg/kg/day

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

clinical observations and clinical chemistry 

alterations indicative of effects on liver/biliary 

function in both sexes.

870.3200

21-Day dermal toxicity in 

rats

43678137 (1994)

Acceptable/guideline

M & F: 0, 200, 500, 1000

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

LOAEL > 1000 mg/kg/day.

870.3700a

Prenatal developmental in 

rats

43678142 (1994)

Acceptable/guideline

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

Maternal NOAEL = 25 mg/kg/day

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

clinical signs of increased diarrhea, urinary 

incontinence, and salivation.

Developmental NOAEL = 100 mg/kg/day

LOAEL > 100 mg/kg/day.

870.3700b

Prenatal developmental in 

rabbits

44058701 (1995)

Acceptable/guideline

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

Maternal NOAEL = 150 mg/kg/day

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

weight gain.

Developmental NOAEL = 500 mg/kg/day
Azoxystrobin Human Health Risk Assessment DP No. 394285

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

Study Guideline/Study MRID Results

LOAEL > 500 mg/kg/day.

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 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 

43678147 (1992)

Acceptable/guideline

The in vitro test in human lymphocytes was positive

for the induction of chromosomal aberrations in both 
Azoxystrobin Human Health Risk Assessment DP No. 394285

Page 33 of 36

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

Study Guideline/Study MRID Results

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/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. 394285

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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 POW = 2.5

UV/visible absorption spectrum Not available
Azoxystrobin Human Health Risk Assessment DP No. 394285

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Appendix C. International Residue Limit Status Sheet.

Azoxystrobin (PC Code 128810; 10/13/11)

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

Residue Definition: 

US Canada Mexico2 Codex3

40 CFR 180.507:

Plant: sum of azoxystrobin, [methyl( E )-

2-(2-(6-(2-cyanophenoxy) pyrimidin-4-

yloxy)phenyl)-3-methoxyacrylate], and 

the Z-isomer 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)benze

neacetate,

including the isomer (Z)-

methyl 2-[[6-(2-

cyanophenoxy)-4-

pyrimidinyl]oxy]--

(methoxymethylene)benz

eneacetate

Azoxystrobin.

The residue is fat 

soluble. 

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

US Canada Mexico2 Codex3

Sugarcane, cane 0.2

Completed: M. Negussie; 10/14/2011 

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 = postharvest treatment, such as treatment of stored grains. PoP = 

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

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.
Azoxystrobin Human Health Risk Assessment DP No. 394285

Page 36 of 36

Appendix D. Review of Human Research

Studies reviewed for ethical conduct:

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

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

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

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

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

June 21, 2011.

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