UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

MEMORANDUM 

Date: December 4, 2015 

SUBJECT: Azoxystrobin: Human Health Draft Risk Assessment for Registration Review 

PC Code: 128810 

Decision No.: 511551 

Petition No.: NA 

DP Ba rcode: 0430443 

Registration No.: NA 

Regulatory Action: Registration Review 

Risk Assessment Type: Aggregate Risk Assessment Case No.: 7245 

TXR No.: NA CAS No. : 13 1860-33-8 

MRID No.: NA 40 CFR: § 180.507 

FROM: 

THROUGH: 

TO: 

Kristin Rury, Biologist ¥-~ /J,f'/ · C _ Whang Phang, Senior To icol ~~ ~ ~ --

Meheret Negussic, Chemist lfe/.e.,,-ef- μe~ 

Risk Assessment Branch 3 (RAB 3) 

Health Effects Division (7509P) 

Risk 

i~ Assessthy C. 

m

Dole

ent 

, 

and 

Industria

Science 

l Hygien

Support 

ist 

Branch 

-;--~ (RASSB{' C •~ Antimicrobials Division 

~i tine Otinger, Branch Chief ~/j Risk Assessment Branch 3 (RAB 3) /#._ - ... __ _..;.... __ _ Health Effects Division (7509P) 

Veronica Dutch, Risk Manager Reviewer 

Jill Bloom, Team Leader 

Pesticide Re-evaluation Division (PRO) (7508P) 

As part of Registration Revi ew, PRD of the Office of Pesticide Programs (OPP) has requested 

that HED evaluate the hazard and exposure data and conduct occupational and residential 

exposure assessments, as needed, to estimate the risk to human health that will result from the 

currently registered uses of pesticides. This memorandum serves as HED's dra ft human health 

risk assessment of the dietary, occupational, and residential exposure; and aggregate risk from 

Page 1 of 75 
the registered uses of azoxystrobin. The most recent quantitative human health risk assessment 

was performed in 2015 (K. Rury, 0423691 and 0418374, 04/07/2015). The following risk 

assessment updates have been made: 

• A route-specific inhalation toxicity study using formulated azoxystrobin was 

incorporated into the toxicity database and selected for inhalation risk assessment; 

• The registered antimicrobial uses of azoxystrobin have been reevaluated according to 

current policies; 

• The registered residential uses of azoxystrobin have been reevaluated using the updated 

inhalation risk assessment point of departure and the revised Residential Standard 

Operating Procedures (SOPs); 

• An aggregate exposure assessment was completed, including updated residential 

exposure estimates; 

• A non-occupational spray-drift exposure/risk assessment was completed; and 

• An occupational exposure assessment for the registered uses was completed reflecting 

recent updates to the azoxystrobin risk assessment points of departure, HEO's SOPs, and 

policy changes for body weight assumptions. 

A summary of the findings and an assessment of human risk resulting from the registered uses of 

azoxystrobin are provided in this document. 

Page 2of75 
Page 3 of 75

1.0 Executive Summary ........................................................................................................... 5

2.0 HED Conclusions and Recommendations....................................................................... 9

2.1 Data Deficiencies......................................................................................................... 9

2.2 Tolerance Considerations .......................................................................................... 9

2.2.1 Enforcement Analytical Method ............................................................................... 9

2.2.2 Recommended Tolerances....................................................................................... 10

2.2.3 International Harmonization................................................................................... 11

2.2.4 Label Recommendations from Occupational Assessment.................................... 11

2.2.5 Label Recommendations from Residential Assessment........................................ 11

3.0 Introduction...................................................................................................................... 11

3.1 Chemical Identity ..................................................................................................... 12

3.2 Physical Chemical Properties.................................................................................. 12

3.3 Pesticide Use Pattern................................................................................................ 13

3.4 Anticipated Exposure Pathways.............................................................................. 16

3.5 Consideration of Environmental Justice ................................................................ 16

4.0 Hazard Characterization and Dose-Response Assessment.......................................... 17

4.1 Toxicology Studies Available for Analysis ............................................................. 17

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME) ......................... 17

4.2.1 Dermal Absorption................................................................................................... 18

4.3 Toxicology Effects.................................................................................................... 18

4.4 Safety Factor for Infants and Children (FQPA Safety Factor)............................ 19

4.4.1 Completeness of the Toxicity Database .................................................................. 19

4.4.2 Evidence of Neurotoxicity ........................................................................................ 20

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal........ 20

4.4.4 Residual Uncertainty in the Exposure Database ................................................... 20

4.5 Toxicity Endpoint and Point of Departure Selections........................................... 21

4.5.1 Dose-Response Assessment...................................................................................... 21

4.5.2 Recommendations for Combining Routes of Exposure for Risk Assessment..... 23

4.5.3 Cancer Classification and Increased Tumor Incidence Risk Assessment 

Recommendation..................................................................................................................... 24

4.6 Endocrine Disruptor Screening Program .............................................................. 24

5.0 Dietary Exposure and Risk Assessment......................................................................... 25

5.1 Residues of Concern Summary ............................................................................... 25

5.2 Food Residue Profile ................................................................................................ 25

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

5.4 Dietary Assessment – Conventional Agricultural Uses......................................... 26

5.4.1 Description of Residue Data Used in Dietary Assessment.................................... 26

5.4.2 Percent Crop Treated Used in Dietary Assessment .............................................. 27

5.4.3 Acute Dietary Risk Assessment............................................................................... 27

5.4.4 Chronic Dietary Risk Assessment........................................................................... 27

5.4.5 Summary Table......................................................................................................... 27

5.5 Dietary Exposure – Antimicrobial Uses ................................................................. 28

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

6.1 Residential (Non-Occupational) Handler Risk ...................................................... 28

6.1.1 Residential Handler Risk – Conventional Uses ..................................................... 28

6.1.2 Residential Handler Risk – Antimicrobial Uses .................................................... 30
Page 4 of 75

6.2 Residential Post-Application Exposure/Risk Estimates........................................ 31

6.2.1 Residential Post-Application Exposure/Risk Estimates – Conventional Uses.... 31

6.2.2 Residential Post-Application Exposure/Risk Estimates – Antimicrobial 

Azoxystrobin Uses................................................................................................................... 33

6.3 Residential Risk Estimates for Use in Aggregate Assessment.............................. 35

6.4 Residential Bystander Post-Application Exposure................................................ 36

7.0 Non-Occupational Spray Drift Exposure and Risk Estimates .................................... 36

8.0 Aggregate Exposure/Risk Characterization.................................................................. 37

7.1 Acute Aggregate Risk............................................................................................... 37

7.2 Short-Term Aggregate Risk .................................................................................... 38

7.3 Intermediate-Term Aggregate Risk........................................................................ 38

7.4 Chronic Aggregate Risk........................................................................................... 38

7.5 Cancer Aggregate Risk ............................................................................................ 39

9.0 Cumulative Exposure/Risk Characterization ............................................................... 39

10.0 Occupational Exposure/Risk Characterization ............................................................ 39

10.1 Short- and Intermediate-Term Handler Risk – Conventional Azoxystrobin Uses

39

10.2 Short- and Intermediate-Term Handler Risk – Antimicrobial Uses................... 42

10.3 Occupational Post-Application Exposure/Risk Estimates.................................... 42

10.3.1 Occupational Post-Application Inhalation Exposure/Risk Estimates................. 43

10.3.2 Occupational Post-Application Dermal Exposure/Risk Estimates...................... 44

11.0 Public Health and Pesticide Epidemiology Data........................................................... 45

12.0 References......................................................................................................................... 46

Appendix A. Toxicology Profile and Executive Summaries .................................................. 48

A.1 Toxicology Data Requirements ............................................................................... 48

A.2 Toxicity Profiles........................................................................................................ 49

Appendix B. Physical/Chemical Properties............................................................................. 52

Appendix C. Review of Human Research................................................................................ 53

Appendix D. Occupational Exposure/Risk Summary Tables................................................ 54

Appendix F. Calculation of Inhalation Human-Equivalent Concentrations (HECs) and 

Human-Equivalent Doses for Azoxystrobin............................................................................. 73
Page 5 of 75

1.0 Executive Summary

The Health Effects Division (HED) and the Antimicrobials Division (AD) have conducted a 

human health draft risk assessment (DRA) to evaluate all existing registrations of the active 

ingredient (ai) azoxystrobin, an β-methoxyacrylate fungicide used to control mold and fungus on 

agricultural crops, agricultural seeds, residential areas, and on indoor surfaces. This assessment 

was conducted as part of Registration Review. 

Use Profile

Azoxystrobin is currently formulated as liquid, dry flowable, granular, and dust end-use products 

(EUPs) containing between 0.31% and 50% ai. Azoxystrobin is registered for use on numerous 

fruit and vegetable crops growing in both fields and greenhouses. Azoxystrobin is also 

registered for use on bananas, plantains, citrus, and tuberous and corm vegetables as a postharvest treatment. Azoxystrobin may also be used on golf course turf, lawns, sports fields, 

ornamentals, conifers, roses, cut flowers, interior plantscapes, and sod. Seed treatment uses of 

azoxystrobin include the following commodities: barley; Brassica (cole) leafy vegetables, crop 

group 5; bulb vegetables, crop group 3; canola; corn (field, pop, sweet); cotton; cucurbit 

vegetables, crop group 9; eggplant; leafy vegetables, crop group 4; leaves of root and tuber 

vegetables, crop group 2; legume vegetables (succulent or dried), crop group 6; okra, peanut; 

peppers; potato; rice; root vegetables, crop subgroup 1A; soybean; sunflower; tomato; triticale; 

tuberous and corm vegetables (except potato), crop subgroup 1D; turf; watercress; and wheat. 

The antimicrobial uses of azoxystrobin for mold control on indoor surfaces include material 

preservation in paints and coatings, rubber and plastics, textiles, paper and paperboard products 

and drywall, and as a mold spray inside residential areas including structural wood, subflooring, 

drywall and carpet.

Azoxystrobin may be applied to agricultural commodities using ground, aerial, chemigation, and 

handheld equipment. Handheld application equipment is used in/around residential areas. Seed 

treatment is expected to occur in commercial treatment facilities only. All registered labels 

require occupational handlers to wear baseline personal protective equipment (PPE) and 

chemical resistant gloves. Some labels require the addition of protective eyewear, dust mist 

respirators, coveralls, and aprons. Those products requiring PPE beyond baseline attire and 

chemical resistant gloves are co-formulations with other active ingredients. The restricted entry 

intervals range from 4 hours to 24 hours; those labels requiring REIs longer than 12 hours are all 

co-formulations with other active ingredients. 

Exposure Profile 

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

applied directly to growing crops and following harvest, and application may result in 

azoxystrobin reaching surface and ground sources of drinking water. In an occupational setting, 

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

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

fields. In a residential setting, residential adult handlers may be exposed while handling 

azoxystrobin, and adults and children may be exposed following application of azoxystrobin 
Page 6 of 75

both indoors and outdoors. Non-occupational exposure resulting from spray drift from 

agricultural applications onto residential areas may also occur. 

Hazard Characterization

The azoxystrobin database is complete for risk assessment, with the exception of a subchronic 

inhalation toxicity study on technical azoxystrobin. In repeat-dose oral studies, the liver and bile 

ducts were consistently the target organs of azoxystrobin toxicity. Developmental effects were 

not seen in rabbit or rat developmental toxicity studies. In the rat reproduction study, offspring 

and parental effects (decreased body weight and increased adjusted liver weight) were observed 

at the same dose in both offspring and parental animals. Therefore, the azoxystrobin toxicity 

data show no increased susceptibility in the young. The dietary and incidental oral points of 

departure (PODs) and levels of concern (LOCs) have not changed since the previous risk 

assessment. A dermal POD has not been selected because there was no dermal or systemic 

toxicity seen up to the limit dose in a route-specific dermal toxicity study, and no developmental 

or reproductive effects were seen in the azoxystrobin database. However, for short- and 

intermediate-term inhalation exposure assessment, the POD was selected during Registration 

Review based on a route-specific inhalation toxicity study in rats with the soluble concentrate 

(SC) formulation of azoxystrobin. For inhalation exposures, the standard interspecies 

extrapolation uncertainty factor (UF) can be reduced from 10X to 3X due to the calculation of 

human equivalent concentrations (HECs) accounting for pharmacokinetic (not 

pharmacodynamic) interspecies differences. For intraspecies variation, 10X is applied. An 

additional 10X is applied for a database uncertainty factor to account for the requirement for an 

inhalation toxicity study on the technical active ingredient (a.i.) because the available 28-day 

inhalation study was tested on only approximately 8% a.i., whereas most of the marketed 

products contained 30 - 50% a.i. Therefore, the level of concern (LOC) for inhalation exposures 

is a margin of exposure (MOE) less than 300 (3X for interspecies extrapolation, 10X for 

intraspecies variation, and 10X for database uncertainty). 

Azoxystrobin is characterized as "not likely" to be a human carcinogen. The Food Quality 

Protection Act (FQPA) Safety Factor (SF) has been reduced to 1X for non-acute exposure 

durations and non-inhalation exposure routes. For assessing acute risk, EPA is retaining a

FQPA safety factor (SF) of 3X to account for the use of a lowest observed adverse effect level 

(LOAEL) from the acute neurotoxicity study to derive an acute reference dose. Azoxystrobin 

exhibits low acute mammalian toxicity via oral, dermal, and inhalation routes of exposure 

(Category III or IV for acute lethality and irritation studies) and is not a dermal irritant or 

sensitizer.

Residue Chemistry

The residue chemistry database is adequate to support current Registration Review data 

requirements. Adequate metabolism (crops, livestock, and rotational crops), storage stability, 

magnitude of the residue, and processing data are available to support the registered uses. 

Adequate methods are available for enforcement of the currently established tolerances. 

Dietary Exposure Assessment

A slightly refined acute dietary analysis was conducted based on the assumption that 

azoxystrobin residues are present at tolerance-levels for all commodities, except citrus fruits 
Page 7 of 75

(which used the highest residues from residue trials), and the assumption that 100% of registered 

crops are treated. The chronic assessment was based on the assumption of tolerance-level 

residues for all commodities, average percent crop treated (%CT) estimates and default 

processing factors were assumed when available. Estimated Drinking Water Concentrations 

(EDWCs) were provided by the Environmental Fate and Effects Division (EFED) and 

incorporated directly into the dietary exposure analysis.

Acute and chronic dietary exposure and risk estimates are below HED’s LOC for the U.S. 

population and all population subgroups. Combined acute dietary exposure from food and 

drinking water at the 95th percentile of exposure is equivalent to 16% of the acute population 

adjusted dose (aPAD) for the general U.S. population. The population subgroup with the highest 

estimated acute dietary exposure is children 1-2 years old, with an estimated exposure at the 95th

percentile equivalent to 40% of the aPAD. 

The chronic dietary exposure estimates are 6% of the chronic population adjusted dose (cPAD)

for the general U.S. population and 15% of the cPAD for children 1-2 years old, the most highly 

exposed population subgroup. 

Azoxystrobin is considered “not likely to be carcinogenic to humans”; therefore a cancer dietary 

risk assessment was not conducted. 

Residential Exposure and Risk Assessment – Conventional Uses 

There is potential residential exposure from the existing conventional uses of azoxystrobin. All 

existing conventional residential uses were previously reassessed to reflect HED’s 2012 

Residential SOPs1(K. Rury, DP394287, 03/30/2012; K. Rury, D418012 and D423847, 

12/17/2014). However, the inhalation PODs have changed since the previous assessment. 

Therefore, the conventional inhalation scenarios have been reevaluated to incorporate changes to

the azoxystrobin toxicity database. Some of the residential handler inhalation risk estimates for 

the registered conventional uses of azoxystrobin are of concern (MOE < 300). However, the 

registered residential conventional uses of azoxystrobin do not result in any risks of concern for 

post-application incidental oral exposures. 

Residential Exposure and Risk Assessment – Antimicrobial Uses 

There is potential residential exposure from the existing antimicrobial uses of azoxystrobin. The 

inhalation PODs have changed since the previous assessment. Therefore, the antimicrobial 

inhalation scenarios have been reevaluated to incorporate changes to the azoxystrobin toxicity 

database. Residential handler inhalation exposures were assessed for applying azoxystrobintreated paint and for applying mold spray. The MOEs are of concern (MOE < 300) for the mold 

spray scenario, and for the airless sprayer and brush/roller painting scenarios for applying 

azoxystrobin treated paints.

There is the potential for residential post application exposure to flooring made from 

azoxystrobin treated vinyl, plastic toys manufactured from azoxystrobin treated plastic, and 

carpets treated with the azoxystrobin mold spray. Incidental oral MOEs for treated/impregnated 

 

1 Available: http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-proceduresresidential-pesticide
Page 8 of 75

vinyl flooring, treated plastic toys, and object-to-mouth exposures from treatments on hard 

surfaces and carpets were not of concern. Residential post-application inhalation MOEs were 

also not of concern for adults or children 1 to < 2 years old following surface directed mold 

sprays. 

Non-Occupational Spray Drift Assessment 

A quantitative spray drift assessment for azoxystrobin is not required because the maximum 

application rate to a crop/target site multiplied by the adjustment factor for drift of 0.26 is less 

than the maximum direct spray residential turf application rate of 0.99 lb ai/A2for any

azoxystrobin products. The turf post-application MOEs have been previously assessed and are 

based on the revised SOPs for Residential Exposure Assessment. 

Aggregate Exposure Assessment – Conventional and Antimicrobial Uses

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

residential pathways; residential exposures for the aggregate assessment include incidental oral 

(only children 1 to <2 years) exposures only. Adult and children inhalation exposures are not 

aggregated with dietary exposures because the effects seen in the inhalation toxicity study (the 

basis for the inhalation POD) are portal of entry effects and differ from those seen in the shortterm oral toxicity studies used for aggregate assessment. For children 1 to <2 years, the shortterm aggregate risk estimates are not of concern; the margin of exposure (MOE) is 300 for 

children 1 to < 2 years old. 

Occupational Exposure – Conventional Agricultural uses

Some occupational handler risk estimates resulted in inhalation MOEs of concern with baseline

PPE; some scenarios resulted in MOEs of concern using maximum levels of PPE or engineering 

controls for agricultural, post-harvest, and seed treatment uses (MOEs < 300). 

Because no dermal POD was selected for azoxystrobin, an occupational post-application 

exposure assessment was not completed. Post-application inhalation exposure following the 

planting of azoxystrobin-treated seeds is unlikely because sustained levels of contact with treated 

seed after placement in soil or other growing media is not expected; therefore post-application 

exposure is expected to be negligible and a quantitative post-application assessment was not 

required for the seed treatment uses of azoxystrobin. Based on the Agency's current practices, a 

quantitative non-cancer occupational post-application inhalation exposure assessment was not 

performed for the outdoor agricultural uses azoxystrobin at this time. If new policies or 

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

post-application inhalation exposure assessment for azoxystrobin. However, there is the 

potential for occupational post-application inhalation exposures in post-harvest treatment 

facilities. There are some occupational post-application inhalation risk estimates of concern for 

the registered post-harvest uses of azoxystrobin at baseline and maximum PPE mitigation (MOE

< 300). 

Occupational Exposure - Antimicrobial Uses

Occupational handler inhalation exposures were assessed for open pouring during paint 

preservation and resulted in a risk estimate of concern (MOE < 300) at baseline. If a PF10 

 

2 0.33 lb ai/A x 0.26 ≤ 0.99 lb ai/A
Page 9 of 75

elastomeric half face respirator is worn, the MOE is increased to 300 and is no longer of concern. 

Application of preserved paint using an airless sprayer and brush/rollers result in risk estimates 

of concern (MOE < 300). These risks cannot be mitigated with respiratory protection because 

only the materials preservative component is an EPA-registered pesticide product; the paints 

themselves are not EPA-registered pesticide products and thus are not required to bear pesticide 

labeling. 

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.3” 

Human Studies

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

intentionally exposed to a pesticide to determine their exposure. Appendix C provides additional 

information on the review of human research used to complete the risk assessment. There is no 

regulatory barrier to continued reliance on these studies, and all applicable requirements of 

EPA’s Rule for the Protection of Human Subjects of Research (40CFR Part 26) have been 

satisfied.

2.0 HED Conclusions and Recommendations

HED is recommending minor commodity definition and significant figure changes to the 

established tolerance values as noted in Section 2.2.2. 

There are some occupational handler and post-application inhalation risk estimates of concern at 

the label-specified PPE. In some cases, additional respiratory protection is not appropriate for 

mitigating inhalation risk estimates of concern. Additionally, some residential handler inhalation 

risk estimates were of concern for the registered uses of azoxystrobin. 

2.1 Data Deficiencies

Toxicology 

HED is recommending that an inhalation toxicity study on technical azoxystrobin be required. 

In absence of that study, a database uncertainty factor will be applied for assessing inhalation 

exposure risks. 

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method 

A gas chromatography method with nitrogen-phosphorus detection (GC/NPD) Method, RAM 

243/04, is available for the enforcement of tolerances for residues of azoxystrobin and its Zisomer in crop commodities. The method has undergone method validation by the Analytical 

 

3

http://www.epa.gov/compliance/environmentaljustice/resources/policy/exec_order_12898.pdf
Page 10 of 75

Chemistry Branch (ACB)/Biological and Economic Analysis Division (BEAD). The method 

was revised to incorporate comments made by BEAD, and the revised method (designated RAM 

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

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

commodities.

Data have previously been submitted pertaining to the multiresidue methods testing of 

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

azoxystrobin could not be recovered through application of the multiresidue protocols. These 

data have been forwarded to FDA for inclusion in PAM I.

Azoxystrobin may be determined by the “Quick Easy Cheap Rugged Effective and Safe”

(QuEChERS) method. 

2.2.2 Recommended Tolerances

Table 2.2.2. Tolerance Recommendations for Azoxystrobin

Commodity

Established 

Tolerance 

(ppm)

Recommended 

Tolerance (ppm) Comments

Tolerance Revisions for Correct Commodity Definition

Grain, aspirated fractions 420 420 Grain, aspirated grain fractions

Tolerance Revisions for Significant Figure

Corn, field, refined oil 0.3 0.30

Cottonseed subgroup 20C 0.7 0.70

Ginseng1 0.5 0.50

Pea and bean, dried shelled, 

except soybean, subgroup 6C

0.5 0.50

Pea and bean, succulent 

shelled, subgroup 6B

0.5 0.50

Peanut 0.2 0.20

Peanut, refined oil 0.6 0.60

Rye, grain 0.2 0.20

Soybean, seed 0.5 0.50

Sugarcane, cane 0.2 0.20

Sunflower subgroup 20B 0.5 0.50

Tomato, paste 0.6 0.60

Tomato subgroup 8-10A 0.2 0.20

Vegetable, root, subgroup 1A 0.5 0.50

Wheat, grain 0.2 0.20

Tolerance Revisions for Significant Figure Changes

Hog, fat 0.010 0.01

Hog, meat byproducts 0.010 0.01
Page 11 of 75

2.2.3 International Harmonization

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

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

whereas the Codex includes only the E isomer.

There are Codex and Canadian maximum residue limits (MRLs) established for residues of 

azoxystrobin. The US and Codex MRLs are in harmony on subgroups 13-07A and 07B, coffee 

bean, cotton seed, cranberry, citrus fruits, grapes, peanut, rice, soybean, sunflower, legume 

vegetables, and wheat. The US livestock tolerances are not harmonized with Codex. The US and 

Canadian tolerances are harmonized for several plant and livestock commodities. 

HED is not proposing revisions to the established tolerances for harmonization purposes. The 

registrant could propose revisions depending on trading priorities. Refer to Appendix C. 

2.2.4 Label Recommendations from Occupational Assessment

Labels vary considerably with respect to requirements for work attire and PPE. For example, 

some labels do not specify any requirements for work attire, while others require respirators and 

coveralls over long-sleeve shirt and long pants. Like work attire and PPE, restricted entry 

intervals (REIs) also vary considerably across labels (e.g., 4 hours versus 48 hours). Thus, label 

corrections/revisions should be consistently made to default to end-use product and/or technical 

grade active ingredient acute (ocular, dermal, oral, and/or inhalation) toxicity requirements. 

Additional PPE, such as respiratory protection, beyond end-use product acute toxicity 

requirements, should be considered as described in the context of any risks of concern identified 

in this assessment.

It is recommended that the material preservation labels be amended to include the use of 

respiratory protection for open pouring.

2.2.5 Label Recommendations from Residential Assessment 

Some azoxystrobin products are intended for use by residential applicators on home lawns or 

residential areas but require certain clothing and/or PPE to be worn. Thus, standard assumptions 

for residential/consumer applicator specific assessments, such as wearing shorts and a t-shirt 

without PPE like chemical-resistant gloves or respirators, would represent non-compliance with 

currently registered products. If products containing azoxystrobin are meant to be marketed 

towards and applied by homeowners on residential turf, ornamentals, and in homes, HED 

recommends that the label requirements for clothing and/or PPE be reevaluated or separate 

consumer-specific labels be developed. 

Note to PRD: It is recommended that the EPA registered label Reg. No. 100-1093 be split into 

two separate labels: one label for conventional uses, and one label for antimicrobial uses that 

would be regulated by AD. 

3.0 Introduction
Page 12 of 75

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

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

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

Azoxystrobin is formulated as liquid, dry flowable, granular, and dust formulated end-use 

products. It can be used on agricultural crops, for treating seed, as a post-harvest application, 

and on outdoor and indoor residential areas. 

The most recent previous risk assessment was completed earlier in 2015 (K. Rury, D423691 and 

D418374, 04/07/2015). 

3.1 Chemical Identity 

Table 3.1. Azoxystrobin Nomenclature.

Compound

Common name Azoxystrobin

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

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

methoxyacrylate

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

benzeneacetate

CAS registry number 131860-33-8

End-use products (EP) Abound® Flowable Fungicide (EPA Reg No. No. 100-1098) containing 22.9% ai

Regulated metabolite, Zisomer

Common name Azoxystrobin, Z-isomer

Company experimental name R230310

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

methoxyacrylate

3.2 Physical Chemical Properties 

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; 

N N

O O

CN OCH3

O

H3CO

N N

O O

CN

O OCH3

H3CO
Page 13 of 75

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

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

azoxystrobin are summarized in Appendix B. 

3.3 Pesticide Use Pattern 

The registered uses and application rates are summarized in Tables 3.3.1 and 3.3.2. 

Table 3.3.1. Summary of Directions for the Agricultural Uses of Azoxystrobin1.

Formulation

Applic. 

Timing, Type, 

and Equip.

Use Site

Max. Single 

Applic. Rate 

(lb ai/A)

Max. Seasonal 

Applic. Rate 

(lb ai/A)

RTI (days)2

Liquid Ground, Aerial, 

Chemigation

Almonds; Artichoke, globe; 

Asparagus; Canberries; Brassica

Head and Stem Subgroup; Bulb 

vegetables; Celery; Citrus; 

Cranberry; Cucurbits; Grapes 13-

07F; Leafy vegetables; Legume 

vegetables; Pistachios; Soybean; 

Stone fruit; Tropical fruit; Wasabi; 

Watercress

0.25 1.5

Bulb vegetables, Cucurbits, 

Leafy vegetables, Vegetables 

root and tuber tuberous and 

corm = >5 

Soybean = NS 

Tropical fruit = 10-14 

All other crops = >7

Bananas/plantains 0.135 1.08 12-14 

Cereal grains (Barley, Oats, Rye); 

Wheat; Triticale 0.2 0.4 NA (max 2 applications)

Bushberry Subgroup 13-07B;

Brassica leafy greens; 0.25 0.75 7-14 

Low growing berries; Fruiting 

vegetables; 0.25 1.0 >7

Canola 0.25 0.45

Make one application at early 

bud, one at 45 days pre 

harvest, and one at 30 days 

pre harvest

Carrots, Potatoes; Vegetables, 

leaves of root and tuber group and 

root subgroup; Vegetables, tuberous 

and corm group

0.33 2.0 7-14

Liquid

Ground, Aerial, 

Chemigation

Chickpeas 0.18 N/S NS

Christmas Trees; Corn (field, pop, 

sweet seed); Conifers; Roses; 0.25 2.0 >7

Cotton 0.15 0.4 14-21

Air and ground Filberts 0.2 N/S NS

Ground, Aerial, 

Chemigation Grasses grown for seed; Mint 0.25 0.8 Grasses = 10-14 Mint = 7-10 

Ground only Herbs and spices 0.25 1.5 7

Ground, Aerial, 

Chemigation

Non-grass animal feeds, forage, 

fodder, straw, and hay 0.25 0.25 NS

Oilseeds, Crop Group 20 0.25 0.4 NS

Onion (green, dry, and bunching) 0.23 N/S N/S

Peanuts 0.4 0.8 NS (ground directed)

10-14 (foliar)

Pecans; Tree nuts; 0.20 1.2 7-21
Page 14 of 75

Table 3.3.1. Summary of Directions for the Agricultural Uses of Azoxystrobin1.

Formulation

Applic. 

Timing, Type, 

and Equip.

Use Site

Max. Single 

Applic. Rate 

(lb ai/A)

Max. Seasonal 

Applic. Rate 

(lb ai/A)

RTI (days)2

Rice; Wild rice 0.3 0.7 7-14

Sorghum 0.25 0.75 NS

Sugarcane 0.2 0.8 14-28

Tobacco 0.2 0.52 7-14

Tomato, subgroup 8-10A 0.1 0.6 7-21

Post-harvest bananas/plantains 0.00034 lb 

ai/gal NA NA

Post-harvest citrus 0.148 lb 

ai/gal NA NA

Post-harvest tuberous and corm 

vegetables

0.00000049 

lb ai/lb NA NA

Golf course turf; Lawns; Sports 

Fields 0.99 NS >10

Ornamentals 0.24 NS 7-14

Cut flowers 0.06 NS >7

Greenhouse ornamentals 0.26 NS >7

Greenhouse vegetables 0.18 NS >7

Greenhouse tomatoes 0.10 NS 7-10

Liquid Seed Treatment 

Equipment

Barley, Bell Pepper, Brassica, Bulb 

Vegetables, Corn (field, pop, 

sweet), Cotton, Cucurbits, 

Eggplant, Leafy Vegetables, 

Legume Vegetables, Non-Bell 

Pepper, Okra, Ornamental Bulbs, 

Ornamental Seed, Peanuts, Potato, 

Root Vegetables, Sunflower, 

Sorghum, Tomato, Triticale, 

Tuberous and Corm Vegetables, 

Turf, Watercress, Wheat 

0.000244 (lb 

ai/lb seed) NA NA

Rice 0.000070 (lb 

ai/lb seed) NA NA

Soybean 0.00003 (lb 

ai/lb seed) NA NA

Cotton 0.00018 (lb 

ai/lb seed) NA NA

Dry Flowable

Ground, Aerial, 

Chemigation, 

Handheld (if 

applicable)

Almonds; Artichoke, globe; 

Asparagus; Caneberries; Brassica

Head and Stem Subgroup; Bulb 

vegetables; Celery; Legume 

Vegetables, dry and succulent; 

Citrus; Cranberry; Cucurbits; 

Grapes 13-07F; Leafy Vegetables; 

Pistachios; Soybean; Stone fruit; 

Tropical Fruit; Watercress

0.25 1.5

Bulb vegetables, cucurbits, 

leafy vegetables, = >5 

Grapes, Tropical fruit = >10 

Soybeans = NS

All other crops = >7

Bananas/Plantains 0.135 1.08 12-14

Dry Flowable Cereal Grains; Wheat; Triticale 0.2 0.4 NS
Page 15 of 75

Table 3.3.1. Summary of Directions for the Agricultural Uses of Azoxystrobin1.

Formulation

Applic. 

Timing, Type, 

and Equip.

Use Site

Max. Single 

Applic. Rate 

(lb ai/A)

Max. Seasonal 

Applic. Rate 

(lb ai/A)

RTI (days)2

Bushberry Subgroup 13-07B; 

Brassica leafy greens; Mint 0.25 0.75 >7

Strawberry; Fruiting Vegetables 

except tomatoes 0.25 1.00 >7

Canola 0.125 0.86 NS

Carrots 0.33 0.48 7-14

Christmas trees; Corn (field, pop, 

seed, sweet); Conifers; Roses 0.25 2.00 >7

Cotton 0.15 NA One application per season

Dry Flowable

Ground, Aerial, 

Chemigation Grasses grown for seed 0.25 0.8 10-14

Ground only Herbs and Spices 0.25 1.5 7

Ground, 

Chemigation Wasabi 0.25 NS NS

Ground, Aerial, 

Chemigation

Oilseeds crop group 20 0.25 0.45 NS

Peanuts – soilborne 0.4 8.0 NS

Peanuts – foliar 0.3 10-14

Potatoes; Vegetables, leaves of root 

and tuber; Vegetables, tuberous and 

corm

0.33 2.0 >5

Rice 0.3 0.7 7-14

Tomatoes 0.1 0.8 >5

Tree Nuts 0.2 1.2 7-21

Turf 0.95 NS NS

Ornamentals 0.04 0.0125 NS

Post-Harvest 

Spray 

Equipment

Post-Harvest Bananas/Plantains 400 (ppm) NA NA

Seed Treatment 

Equipment Cotton 0.0002 lb ai/lb seed NA NA

Granular Ground, Aerial, 

Handheld Turf, Lawn and Golf course 0.95 5.0 14-28

Dust Seed Treatment 

Equipment Peanuts 0.00008 lb ai/lb seed NA NA

1. NS = Not specified, NA = Not applicable

2. RTIs are based on the following representative labels: 

a. Liquid: EPA Reg. No. 89442-21 

b. Liquid greenhouse: EPA Reg. No. 100-1506 

c. Dry Flowable: EPA Reg. No. 100-1093 

d. Granulars: EPA Reg. No. 100-1275

Table 3.3.2. Azoxystrobin Antimicrobial Uses. 

Use Application Rate Application 

Method Comment

Material Preservation Uses

Ceiling Tiles 0.048 to 0.33% ai in in wet slurry Open Pour 

Liquid N/A

Latex Caulks, Sealants, Adhesives 0.015 to 0.305% ai Open Pour N/A
Page 16 of 75

Table 3.3.2. Azoxystrobin Antimicrobial Uses. 

Use Application Rate Application 

Method Comment

and Binders Liquid

Textiles, Fabrics, Canvas and 

Cordage 0.015 to 0.23% ai Open Pour Liquid Not for apparel

Rubber and Plastic Products 0.076 to 0.23% ai Open Pour 

Liquid

Not for use in food and beverage 

containers including plastic piping 

carrying water or beverages and piping 

for food processing equipment

Paints, Stains and Coatings 0.029 to 0.305% ai Open Pour

Liquid N/A

Paper, Wallboard and Paperboard 

Products 48 to 190 ppm ai in dry paper Open PourLiquid N/A

Residential and Public Access Premises

Indoor Residential Mold Spray 0.0078 lb ai per gallon Handwand 

Sprayer EPA Registration #100-1093

3.4 Anticipated Exposure Pathways 

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

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

and ground sources of drinking water. In an occupational setting, applicators may be exposed 

while handling the pesticide prior to application as well as during application. There is also 

potential for post-application exposure for workers re-entering treated fields. In residential 

settings, adult handlers may be exposed during application of azoxystrobin, and adult and 

children may be exposed following application. There is a potential for spray drift that may 

result in exposures in residential and non-occupational settings.

This risk assessment considers all of the aforementioned exposure pathways based on the

existing uses of azoxystrobin.

3.5 Consideration of Environmental Justice 

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

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

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

(http://www.epa.gov/environmentaljustice/resources/policy/exec_order_12898.pdf). As a part of 

every pesticide risk assessment, OPP considers a large variety of consumer subgroups according 

to well-established procedures. In line with OPP policy, HED estimates risks to population 

subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water 

consumption, and activities in and around the home that involve pesticide use in a residential 

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

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

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

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

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

exposure assessments are performed when conditions or circumstances warrant. Whenever 

appropriate, non-dietary exposures based on home use of pesticide products and associated risks 
Page 17 of 75

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

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

exposure and it was considered in this analysis. Further considerations are also currently in 

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

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

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

4.0 Hazard Characterization and Dose-Response Assessment 

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

available database to establish points of departure for the risk assessment. A detailed discussion 

of certain POD selections (acute dietary, chronic dietary, dermal, and incidental oral) is 

presented in the previous azoxystrobin risk assessment (K. Rury, D389702, 12/18/2012). The 

inhalation POD has been revised by the risk assessment team since the previous assessment. 

4.1 Toxicology Studies Available for Analysis 

The toxicology data for azoxystrobin are sufficient and adequate for selecting toxicity endpoints 

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

 Subchronic oral toxicity studies in rats and dogs,

 21- Day dermal toxicity study in rats,

 28-Day inhalation toxicity study with SC formulation,

 Developmental toxicity studies in rats and rabbits,

 2-Generation reproduction study in rats,

 chronic toxicity study in dogs,

 Carcinogenicity study in mice and Combined chronic toxicity/carcinogenicity study in 

rats,

 A battery of the required genotoxicity studies,

 Metabolism study in rats,

 Acute and subchronic neurotoxicity studies, and

 Dermal penetration study in rats

HED recommended that the required immunotoxicity study not be required based on the 

evaluation of entire toxicity dataset which indicated no potential for immunotoxicity (TXR 

0057071).

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

Following oral administration azoxystrobin was absorbed and distributed broadly. Biliary 

excretion data suggested that approximately 70% of administered dose was absorbed while 

approximately 32% remained in gastrointestinal tract and was eliminated as the parent compound. 

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

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

administered dose was detected in the tissues examined, including liver and kidney, on the 7th

day after dosing which suggests minimal potential for bioaccumulation. There were no apparent 

sex-related differences in distribution. The absorbed azoxystrobin appeared to be extensively 
Page 18 of 75

metabolized. A metabolic pathway, consistent with the data on metabolite identification and 

quantitation, was proposed showing hydrolysis and subsequent glucuronide conjugation as the 

major biotransformation process. A total of 15 metabolites were detected in the excreta and 

subsequently identified. The glucuronide conjugate (metabolite V) was the most prevalent 

biliary metabolite in both males and females. The primary route of elimination was via the feces 

(73-89% of the administered dose) followed by the urine (9-18%). The fecal vs. urinary route 

of excretion did not vary considerably with dose. There were no apparent sex- or dose-related 

differences in the pattern of excretion. 

4.2.1 Dermal Absorption 

In an acceptable dermal absorption study with 24 male rats, percutaneous absorption was 

minimal (< 4.2%). Time-course data indicated that most absorption occurred during the first 0.5 

hours and that this represented approximately 0.9% of the administered dose. The low dermal 

absorption was also supported by the results of a 21-day rat dermal toxicity study, where no adverse 

effects were seen up to the limit dose (1,000 mg/kg/day).

4.3 Toxicology Effects

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

azoxystrobin. Liver and biliary effects were seen in rats (increased liver weights, gross and 

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

observations including fluid feces and salivation) and clinical chemistry alterations (including 

increased serum levels of alkaline phosphatase, and gamma-glutamyl transferase; and decreases 

in serum albumin). These effects seen are indicative of changes to liver/biliary function. 

Decreased body weight (rats and mice) and decreased body weight gain (rats and rabbits) were 

also consistent findings across studies and species. Other effects including decreased food 

intake/utilization, increased diarrhea and other clinical toxicity observations such as urinary 

incontinence, salivation, hunched postures and distended abdomens were also seen in various 

studies (developmental toxicity, reproduction, and 90 day oral toxicity) in rats. Inhalation 

exposure to a soluble concentrate (SC) formulation of azoxystrobin resulted in adverse 

microscopic changes in the nasal cavity and larynx.

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

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

reproduction study, decreased body weights and increased adjusted liver weights were observed 

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

increased susceptibility in the young. 

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

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

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

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

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

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

09/03/1998). 
Page 19 of 75

Although azoxystrobin induced a weak mutagenic response in the mouse lymphoma assay (nonlinear, slight but significant increases in the mutation frequency of mouse lymphoma cells), the 

activity expressed in vitro is not expected to be expressed in whole animals (G. Dannan. 

09/25/2000; HED Doc No. 014329). There was no evidence of carcinogenicity in rats and mice 

at acceptable tested dose levels; azoxystrobin is classified as “not likely to be carcinogenic to 

humans.” 

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

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

and is not a skin sensitizer. 

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

For assessing acute dietary risk, EPA is retaining an FQPA factor of 3X to account for the use 

of a LOAEL from the acute neurotoxicity study to derive an acute reference dose. The Agency 

believes that a 3X FQPA SF (as opposed to a 10X) will be adequate to extrapolate a no 

observed adverse effect level (NOAEL) in assessing acute risk based on the following 

considerations:

 The LOAEL is based on a transient effect (diarrhea in rats) expected to be relatively 

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

 The diarrhea was only seen in studies using gavage dosing in the rat, but not in studies using 

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

in rabbits.

 The very high dose level needed to reach the acute oral lethal dose (LD) 50 (>5000 mg/kg), 

and the overall low toxicity of azoxystrobin.

The decision to reduce the FQPA safety factor to 1X for the assessment of the remaining 

exposure scenarios is based on the following findings:

The FQPA SF was reduced to 1X for all other oral exposure scenarios for the following reasons:

 The point of departures (PODs) used for short-term, intermediate-term, and chronic risk 

assessments were based on clearly defined NOAELs.

 No increased susceptibility was seen in rats and rabbits exposed in utero and/or 

postnatally to azoxystrobin.

 The database was complete with exception of considering inhalation route of exposure.

 No residual uncertainty was found in the exposure database.

The details are presented below.

4.4.1 Completeness of the Toxicity Database 
Page 20 of 75

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

and PODs for risk assessment, with the exception of a subchronic inhalation toxicity study on 

technical azoxystrobin. Although a subchronic inhalation toxicity study on soluble concentrate 

(SC) formulation is available, the results of the study indicated adverse microscopic changes 

occurred in the nasal cavity and the larynx at a rather low concentration of the tested formulation 

(approximately 8% of azoxystrobin). In contrast, most of the azoxystrobin formulations 

available in the market contain 30 to 50% azoxystrobin. Therefore, HED recommends requiring 

an inhalation toxicity study on technical azoxystrobin. In absence of that study, a database 

uncertainty factor is to be apply for assessing inhalation exposure risks only. 

4.4.2 Evidence of Neurotoxicity

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

indicative of neurotoxicity as discussed in Section 4.3. There is no need for a developmental 

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

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young 

Animal

No increased susceptibility was seen in rats and rabbits exposed in utero and/or postnatally to

azoxystrobin.

4.4.4 Residual Uncertainty in the Exposure Database 

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

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

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

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

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

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

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

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

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

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

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

assessment utilized water concentration values generated by models and associated modeling 

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

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

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

women of child bearing age. 

In addition, the residential exposure assessments are based on the 2012 Residential SOPs 

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

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

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. 
Page 21 of 75

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose-Response Assessment 

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

available database to establish points of departure for the risk assessment. A detailed discussion 

of certain POD selections (acute and chronic dietary, dermal, and incidental oral) is presented in 

the previous azoxystrobin risk assessments (K. Rury, D389702, 01/18/2012 and K. Rury, 

D423691 and D418374, 04/07/2015). The inhalation PODs have been revised by the risk 

assessment team since the previous assessment. 

Short and intermediate term inhalation exposure: The route specific subchronic inhalation 

study in rats with SC formulation was selected to evaluate inhalation exposures with a NOAEL 

of 3.8 μg/L. The LOAEL of 11.2 μg/L was based on adverse microscopic changes seen in the 

nasal cavity and the larynx. Human equivalent concentrations (HECs) for residential and 

occupational scenarios were derived using the NOAEL and the regional deposited-dose ratio 

(RDDR). The RDDR accounts for the particulate diameter [mass median aerodynamic diameter 

(MMAD) and geometric standard deviation (GSD)] and estimates the different dose fractions 

deposited along the respiratory tract. The RDDR also accounts for interspecies differences in 

ventilation and respiratory tract surface areas. For the subchronic inhalation toxicity study with 

SC formulation, a RDDR was estimated at 0.181 based on the extrathoracic effects seen at the 

LOAEL of 11.2 μg/L, with a MMAD of 3.5 μm and GSD of 2.71.

Human-equivalent doses (HEDs) were subsequently calculated from the HECs for residential 

and occupational handler scenarios. For occupational handlers, human-equivalent doses of 

0.029, 0.059, and 0.103 mg/kg/day correspond to breathing rates of 8.3 L/min, 16.7 L/min, and 

29 L/min. For residential handlers of conventional products, the human-equivalent dose of 0.02 

mg/kg/day is only calculated for the 16.7 L/min breathing rate. For residential handlers of 

antimicrobial products, the human equivalent dose of 0.059 mg/kg/day is calculated for the 16.7 

L/min breathing rate based on 8 hours of handler exposures. HEC and human-equivalent dose 

calculations are summarized in the Appendix F. 

The standard interspecies extrapolation uncertainty factor (UF) can be reduced from 10X to 3X 

due to the calculation of HECs accounting for pharmacokinetic (not pharmacodynamic) 

interspecies differences. For intraspecies variation, 10X is applied. An additional 10X 

uncertainty factor is applied for a database uncertainty factor to account for the requirement for 

an inhalation toxicity study on technical active ingredient and as a FQPA Safety Factor to assess 

inhalation exposure risks to residential handlers and residential post-application exposures. 

Therefore, the level of concern (LOC) for occupational and residential inhalation exposures is an 

MOE less than 300 (3X for interspecies extrapolation, 10X for intraspecies variation, and 10X 

for database uncertainty). 

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

assessment is not needed. 
Page 22 of 75

The toxicity endpoints and points of departure are presented in Tables 4.5.1 and 4.5.2.

Table 4.5.1. Summary of Toxicological Doses and Endpoints for Azoxystrobin for Use in Dietary, NonOccupational Human Health Risk Assessments.1

Exposure/

Scenario Point of Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Acute Dietary

(All 

Populations) LOAEL = 200 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 3X

Acute RfD = 

0.67mg/kg/day

aPAD = 0.67 

mg/kg/day

Acute Neurotoxicity - Rat. 

LOAEL = 200 mg/kg/day based 

on diarrhea at two-hours post 

dose at all dose levels tested.

Chronic 

Dietary (All 

Populations) NOAEL = 18 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Chronic RfD = 

0.18 

mg/kg/day

cPAD = 0.18 

mg/kg/day

Combined Chronic 

Toxicity/Carcinogenicity Feeding 

Study – Rat. LOAEL = 82.4/117 

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

reduced body weights in both 

sexes and bile duct lesions in 

males.

Incidental 

Oral ShortTerm (1-30 

days) & 

Intermediateterm (1-6 

months)

NOAEL = 35 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Residential 

LOC for MOE 

= 100

2-generation reproduction study –

rats 

LOAEL = 165 mg/kg/day based 

on decreased pup weights in both 

males and females (↓8-21%).

Dermal

(All 

Durations)

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

Study – Rat. No dermal or 

systemic toxicity was seen at the 

limit dose (1,000 mg/kg/day).

Inhalation2

(All 

Durations)

Rat inhalation

NOAEL=3.8 μg/L

UFA=3

UFH=10

FQPA SF = 

UFDB=10+

LOC = 300

28-Day inhalation toxicity study 

in rats on SC formulation

LOAEL = 12.2 μg/L based on 

adverse histopathological changes 

in the larynx (squamous 

metaplasia) and nasal cavity 

(metaplasia of the respiratory 

epithelium.). There was an 

increase severity with increases in 

the test concentrations. 

Conventional 

Residential Uses:

HEC3 = 0.688 

mg/cubic meter

HED4 =0.02 

mg/kg/day

(16.7 L/min)

Antimicrobial 

Residential Uses++:

HEC3 = 0.516 

mg/cubic meter

HED4 = 0.059 

mg/kg/day 

(16.7 L/min)

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 
Page 23 of 75

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

Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of 

concern. N/A = not applicable.

2. To protect for the body weight decreases seen in the pups, a 69 kg body weight was used for estimating short- and intermediate-term 

inhalation doses because the pup body weight decrease also influenced by the maternal health. 

3. HEC = rat NOAEL*(daily duration adjustment)*weekly daily duration adjustment *RDDR*

4. HED = HEC*human specific conversion factor*daily duration

+: An inhalation study on active ingredient (a.i.) is recommended. This safety factor is to account for lack of a study with the a.i.

++AD assumes that the exposure duration for residential painting and mold spraying is 8 hours per day (Ventilation rate = 16.7 LPM).

Table 4.5.2. Summary of Toxicological Doses and Endpoints for Azoxystrobin for Use in 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

Dermal

(All 

Durations) No hazard was identified for this exposure scenario.

21-Day Repeated Dose Dermal 

Study – Rat. No dermal or 

systemic toxicity was seen at the 

limit dose (1,000 mg/kg/day).

Inhalation2

(All 

Durations)

Rat inhalation

NOAEL=3.8 μg/L

UFA=3

UFH=10

UFDB=10+

LOC = 300

28-Day inhalation toxicity study in 

rats on SC formulation

LOAEL = 12.2 μg/L based on 

adverse histopathological changes 

in the larynx (squamous 

metaplasia) and nasal cavity 

(metaplasia of the respiratory 

epithelium.). There was an 

increase severity with increases in 

the test concentrations. 

Occupational handler

HEC3 = 0.516 

mg/cubic meter

HED4(mg/kg/day)

0.029 (8.3 L/min)++

0.059 (16.7 L/min) ++

0.103 (29 L/min) ++

Cancer

(oral, dermal, 

inhalation)

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

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

beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed 

adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = extrapolation from animal to human 

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

Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of 

concern. N/A = not applicable.

2. To protect for the body weight decreases seen in the pups, a 69 kg body weight was used for estimating short- and intermediate-term inhalation 

doses because the pup body weight decrease also influenced by the maternal health. 

3. HEC = rat NOAEL*(daily duration adjustment)*weekly daily duration adjustment *RDDR*

4. HED = HEC*human specific conversion factor*daily duration

+: An inhalation study on active ingredient (a.i.) is recommended. This safety factor is to account for lack of a study with the a.i.

++: Three ventilation rates corresponding to three HEDs used for assessing occupational inhalation exposures.

4.5.2 Recommendations for Combining Routes of Exposure for Risk 

Assessment

Human health risk assessment must consider exposures from three major routes: oral, dermal, 

and inhalation exposures. Although azoxystrobin is registered for use in residential areas, the 

inhalation and incidental oral PODs are based on the different effects seen in different routespecific studies; therefore, exposures from these routes should not be combined. No dermal 

hazard was identified in the azoxystrobin database; therefore dermal exposures are not evaluated 

or combined with any other exposure route for occupational and residential handlers and postapplication scenarios and non-occupational spray drift assessments. 
Page 24 of 75

4.5.3 Cancer Classification and Increased Tumor Incidence Risk 

Assessment Recommendation

Azoxystrobin is classified as “Not likely to be Carcinogenic to Humans.” Cancer risk 

assessments do not need to be conducted. 

4.6 Endocrine Disruptor Screening Program

As required by the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal 

Food, Drug, and Cosmetic Act (FFDCA), EPA reviews numerous studies to assess potential 

adverse outcomes from exposure to chemicals. Collectively, these studies include acute, 

subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, 

developmental, reproductive, and general or systemic toxicity. These studies include endpoints 

which may be susceptible to endocrine influence, including effects on endocrine target organ 

histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, 

reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates 

acute tests and chronic studies that assess growth, developmental and reproductive effects in 

different taxonomic groups. As part of its most recent registration decision for azoxystrobin, 

EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment 

scenarios from the existing hazard database. However, as required by FFDCA section 408(p), 

azoxystrobin is subject to the endocrine screening part of the Endocrine Disruptor Screening 

Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

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

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

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

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

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

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of 

chemicals identified for EDSP screening was published on June 14, 20134and includes some 

pesticides scheduled for registration review and chemicals found in water. Neither of these lists 

should be construed as a list of known or likely endocrine disruptors. 

 

4

See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals.
Page 25 of 75

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

chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website.5

5.0 Dietary Exposure and Risk Assessment 

5.1 Residues of Concern Summary 

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

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

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

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

12/30/1998). 

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

Tolerance Expression for Azoxystrobin1

Matrix Residues included in Risk 

Assessment

Residues included in Tolerance 

Expression

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

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

Livestock Ruminant Azoxystrobin Azoxystrobin

Poultry Azoxystrobin Azoxystrobin

Drinking Water Azoxystrobin Not Applicable

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

5.2 Food Residue Profile 

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

assessment and tolerance assessment. 

Crop field trials generally reflect foliar applications. Residues from foliar applications are 

generally quantifiable and significant. Residues do concentrate in some processed commodities 

such as oils (citrus oil, field corn oil, peanut oil) and reduced water content commodities (citrus 

pulp, dried basil, tomato paste). 

Residue chemistry studies are supported by adequate storage stability data which demonstrate 

that azoxystrobin and its Z-isomer are stable for at least 24 months in water-, starch-, protein-, 

oil-, and acid-containing materials under frozen conditions. 

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

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

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

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

 

5 http://www.epa.gov/endo/
Page 26 of 75

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

buckwheat and millet.

5.3 Water Residue Profile 

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

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

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

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

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

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

those modeled with the Pesticide Root Zone Model (PRZM-GW). Water residues were 

incorporated in the Dietary Exposure Evaluation Model software with the Food Commodity 

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

indirect, all sources.” 

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

Assessment.

Scenario

Model

(application rate lb ai/A, 

frequency, interval)

Surface Water

(μg/L) 1

Ground Water 

(μg/L) 

(Acute/Chronic)

Peak

(1-in-10 yr)

365-day 

Average

(1-in-10 yr)

Entire 

Simulation 

Mean

SCI-GROW2

Turf

SWCC

(0.55, 9x, 10 d)

70.2 48.5 38.5 3.1

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

2. SCI-GROW = Screening Concentration In Ground Water

5.4 Dietary Assessment – Conventional Agricultural Uses

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

were previously conducted using DEEM-FCID Version 3.16, which is based on National Health 

and Nutrition Examination Survey (NHANES) 2-day food consumption data from 2003-2008. 

These assessments incorporate all of the existing uses of azoxystrobin; therefore they have not 

been reevaluated here for Registration Review (D422726, S. Funk, 10/29/2014).

5.4.1 Description of Residue Data Used in Dietary Assessment 

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

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

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

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

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

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

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

Crop Group Regulation to other Commodities in Each Crop Group/Subgroup.”
Page 27 of 75

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

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

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

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

concentration. 

The modeled surface water EDWC from the turf application scenario was incorporated directly 

into the dietary assessments (highest EDWC for registered crops). The highest estimates for 

acute exposure, 70.2 ppb, and chronic exposure, 48.5 ppb, were used in the analysis. 

5.4.2 Percent Crop Treated Used in Dietary Assessment

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

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

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

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

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

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

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

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

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

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

40%; potatoes (seed treatment), <1%; pumpkins, 20%; rice, 40%; soybeans, 5%; soybeans (seed 

treatment), <1%; spinach, 10%; squash, 20%; strawberries, 25%; sugar beets, 10%; sugar beets 

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

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

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

5.4.3 Acute Dietary Risk Assessment 

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

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

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

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

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

population subgroup. 

5.4.4 Chronic Dietary Risk Assessment 

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

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

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

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

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

old. 

5.4.5 Summary Table 
Page 28 of 75

Table 5.4.5. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Azoxystrobin1. 

Population Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary

Dietary Exposure 

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

General U.S. Population 0.110459 16 0.010724 6.0

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

Children 1-2 years old 0.269743 40 0.027728 15

Children 3-5 years old 0.228330 34 0.022261 12

Children 6-12 years old 0.129649 19 0.013336 7.4

Youth 13-19 years old 0.094863 14 0.008376 4.7

Adults 20-49 years old 0.096366 14 0.009213 5.1

Adults 50+ years old 0.089088 13 0.009308 5.2

Females 13-49 years old 0.097704 15 0.008883 4.9

1. Dietary exposure estimates remain unchanged since the previous assessment (D423337 and D423720, S. 

Funk, 10/29/2014). The values for the highest exposed population for each type of risk assessment are 

bolded. 

5.5 Dietary Exposure – Antimicrobial Uses 

EPA has established tolerances of azoxystrobin on various fruits and vegetables under Federal 

Food, Drug and Cosmetic Act (FFDCA) Section 408 (40 CFR§180.507). There are no tolerance 

exemptions for azoxystrobin as an active ingredient under FFDCA Section 408. Azoxystrobin 

has not been cleared as a food additive by the US Food and Drug Administration (US FDA) 

under FFDCA Section 409. There are currently no FIFRA-registered antimicrobial uses that 

could result in direct or indirect food contact, thus, antimicrobial uses are not expected to 

contribute to the dietary exposure estimated for the conventional agricultural uses of 

azoxystrobin. Furthermore, the conventional agricultural uses of azoxystrobin do not result in 

dietary exposure risks of concern. Therefore, a quantitative dietary exposure assessment for the 

antimicrobial uses of azoxystrobin is not required during Registration Review.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization 

A residential exposure and risk assessment was completed to include all registered uses of 

azoxystrobin and to incorporate updates to the inhalation POD (K. Rury, D430444, 12/04/2015). 

 

6.1 Residential (Non-Occupational) Handler Risk 

6.1.1 Residential Handler Risk – Conventional Uses

HED uses the term “handlers” to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct tasks related to applications and that 
Page 29 of 75

exposures can vary depending on the specifics of each task. Residential handlers are addressed 

somewhat differently by HED as homeowners are assumed to complete all elements of an 

application without use of any protective equipment. Residential handler exposure is expected to 

be short-term in duration. Intermediate-term exposures are not likely because of the intermittent 

nature of applications by homeowners. The algorithms used to estimate exposure and dose for 

residential handlers can be found in the 2012 Residential SOPs6.

For residential handlers, exposures from application to turf were not combined with exposures 

from treating gardens/trees because concurrent use of separate pesticide products that contain the 

same active ingredient to treat the same or different pests does not typically occur. Additionally, 

combining exposures to these uses is not considered appropriate in light of the already 

conservative assumptions inherent in the assessment. For example, when assessing individual 

short-term residential handler exposure scenarios, EPA assumes exposure occurs to the highest 

registered application rate, day after day, for the same amount of time each day, for up to 30 days 

for short-term exposures. Exposure estimates are compared to points of departure that are 

typically based on weeks of dosing in test animals. Therefore, although the same products allow 

treatment of gardens/trees and turf, these exposures were not combined for residential handlers. 

Some of the residential handler inhalation risk estimates for the registered uses of azoxystrobin 

are of concern. The individual scenarios of concern include: 

 Mixing/loading/applying liquids using a hose-end sprayer to turf, 

 Mixing/loading/applying liquids using a backpack sprayer to turf, 

 Mixing/loading/applying dry flowable formulations using a manually pressurized 

handwand to turf, 

 Mixing/loading/applying a dry flowable formulation using a hose-end sprayer to turf, and 

 Mixing/loading/applying dry flowable formulations using a backpack sprayer to turf. 

 Hand dispersal of granules around/to gardens/trees, 

All other scenarios are not of concern for the registered conventional uses of azoxystrobin in 

residential areas. 

Table 6.1.1. Residential Handler Non-cancer Exposure and Risk Estimates for Azoxystrobin.

Exposure Scenario Formulation

Inhalation Unit 

Exposure 

(mg/lb ai)

Maximum 

Application Rate1

Area Treated 

or Amount 

Handled 

Daily2

Inhalation

Dose 

(mg/kg/day)3

MOE

(LOC = 300)4

Mixer/Loader/Applicator

Manually Pressurized Handwand 

to Gardens/Trees

Liquid

0.018 0.0013 lb ai/gal 5 gal 0.0000015 14,000

Manually Pressurized Handwand 

to Turf 0.018 0.01 lb ai/gal 5 gal 0.000011 1,800

Hose-end Sprayer to 

Gardens/Trees 0.0014 0.0013 lb ai/gal 11 gal 0.00000025 80,000

Hose-end Sprayer to Turf 0.022 0.99 lb ai/A 0.5 acres 0.00014 150

Backpack Sprayer to 0.14 0.0013 lb ai/gal 5 gal 0.000011 1,800

 

6 Available: http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-proceduresresidential-pesticide
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Table 6.1.1. Residential Handler Non-cancer Exposure and Risk Estimates for Azoxystrobin.

Exposure Scenario Formulation

Inhalation Unit 

Exposure 

(mg/lb ai)

Maximum 

Application Rate1

Area Treated 

or Amount 

Handled 

Daily2

Inhalation

Dose 

(mg/kg/day)3

MOE

(LOC = 300)4

Gardens/Trees

Backpack Sprayer to Turf 0.14 0.01 lb ai/gal 5 gal 0.000088 230

Sprinkler Can to Gardens/Trees 0.0014 0.0013 lb ai/gal 5 gal 0.00000011 180,000

Sprinkler Can to Turf 0.022 0.000013 lb ai/ft2 1000 ft2 0.0000036 5,600

Manually Pressurized Handwand 

to Gardens/Trees

Dry Flowable

1.1 0.000125 lb ai/gal 5 gal 0.0000086 2,300

Manually Pressurized Handwand 

to Turf 1.1 0.119 lb ai/gal 5 gal 0.0082 2.4

Hose-end Sprayer to 

Gardens/Trees 0.0014 0.000125 lb ai/gal 11 gal 0.000000024 830,000

Hose-end Sprayer to Turf 0.022 0.95 lb ai/A 0.5 acres 0.00013 150

Backpack Sprayer to 

Gardens/Trees 1.1 0.000125 lb ai/gal 5 gal 0.0000086 2,300

Backpack Sprayer to Turf 1.1 0.119 lb ai/gal 5 gal 0.0082 2.4

Sprinkler Can to Gardens/Trees 0.0014 0.000125 lb ai/gal 5 gal 0.000010 1,900

Sprinkler Can to Turf 0.022 0.0000218 lb ai/ft2 1000 ft2 0.0000060 3,300

Belly Grinder to Turf

Granules

0.039

0.0000218 lb ai/ft2

1200 ft2 0.000013 1,600

Spoon around Gardens/Trees 0.087 1200 ft2 0.000028 700

Spoon to Turf 0.087 100 ft2 0.0000024 8,400

Cup around Gardens/Trees 0.013 1200 ft2 0.000043 4,700

Cup to Turf 0.013 100 ft2 0.00000035 56,000

Hand Dispersal around 

Gardens/Trees 0.38 1200 ft2 0.00012 160

Hand Dispersal to Turf 0.38 100 ft2 0.000010 1,900

Shaker Can around

Gardens/Trees 0.013 1200 ft2 0.0000043 4,700

Shaker Can to Turf 0.013 100 ft2 0.00000035 56,000

1. Shaded MOEs indicate risk estimates of concern (MOE < 300). 

2. Based on HED’s 2012 Residential SOPs (http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/standardoperating-procedures-residential-pesticide).

3. Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre, gal, or ft2) × Area Treated or Amount 

Handled (A/day, gallons/day, or ft2/day) ÷ BW (80 kg).

4. Inhalation MOE = Inhalation HED (0.02 mg/kg/day) ÷ Inhalation Dose (mg/kg/day). LOC = 300. 

6.1.2 Residential Handler Risk – Antimicrobial Uses 

Treated Paint

All three of the antimicrobial end use products that are used for material preservation are added 

to paints. There is potential for residential handler exposure during the application of paints

treated with azoxystrobin as a preservative. The exposure duration is assumed to be short-term 

because it is likely that a residential painter would apply paints for a few days at a time and for 8 

hours per day. 

The MOEs for residential handlers of azoxystrobin preserved paints are summarized in Table 

6.1.2.1. The MOEs are less than the LOC of 300 for both the airless sprayer and brush/roller 
Page 31 of 75

scenarios, which means that the risks are of concern. These risks cannot be mitigated with 

respiratory protection because preserved paints are not EPA registered pesticide products and 

thus do not have labels that could include PPE requirements. 

Antimicrobial Mold Spray

There is one product (EPA Reg. No. 100-1093) registered for indoor residential mold spray use. 

The label indicates that the product can only be used by residential applicators as a preventative 

treatment on up to 800 square feet and for remediation of areas of 10 square feet or less. This 

product is not for use by professional or commercial applicators. There is the potential for 

residential handler inhalation exposure during mold remediation treatments that are applied as a 

spray to wood, drywall, carpets, and non-food hard non-porous surfaces. 

The unit exposures, application rates and amounts of products applied per day were used to 

calculate MOEs as shown in Table 6.1.2.2. The MOE is less than 300 and the risks are of 

concern.

6.2 Residential Post-Application Exposure/Risk Estimates

6.2.1 Residential Post-Application Exposure/Risk Estimates – Conventional 

Uses

Table 6.1.2.1 Azoxystrobin Residential Handler Inhalation MOEs for Preserved Paint 

Scenario Application 

Rate1

Amount Paint 

Applied (lb/day)2

Amount 

Ai 

Handled 

(lb/day)

Unit 

Exposure

(mg/lb ai)3

Daily Dose4

(mg/kg/day)

Inhalation 

MOE5

(LOC =300)

Application of Paint Containing Azoxystrobin

Airless sprayer 

0.31% ai by wt

150 

(15 ga x 10 lb/ga) 0.47 0.56 0.0033 18

Brush/Roller 20

(2 ga x 10 lb/ga) 0.047 0.20 0.00012 170

1. Based upon maximum rate listed on label EPA Reg. No. 39967-86. 

2. HED Standard Operating Procedures (SOPs) for Residential Exposure Assessment (October 22, 2012).

3. HED Occupational Pesticide Handler Unit Exposure Surrogate Reference Table (March, 2013)

4. Daily Dose = [Amount ai Handled (lb) * Unit Exposure (mg/lb)]/ Body Weight (80 kg)

5. MOE = HED (0.059 mg/kg/day for an 8 hour exposure at 16.7 liters/minute) / Daily Dose (mg/kg/day). Shaded MOEs represent risk estimates of 

concern (MOE < 300). 

Table 6.1.2.2. Azoxystrobin Residential Handler Inhalation MOEs for Mold Spray Treatment 

Scenario

Application 

Rate1

(% a.i.)

Amount 

Product 

Applied per 

Day2

Amount Ai 

Handled3

(lb/day)

Unit 

Exposure4

(mg/lb ai)

Daily Dose5

(mg/kg/day)

Inhalation 

MOE6

(LOC = 300)

Low Pressure 

Handwand in Indoor 

Environments

0.0078 lb ai per 

gallon 10 gallons 0.078 1.1 0.0011 54

1. Based on the label directions (2.6 solid ounces of product added to 10 gallons of water) and 50% a.i. in the product.

2. Based on the label directions.

3. Amount ai handled = Application Rate (lb ai/gallon) *Gallons Applied 

4. Unit Exposure Value for Mix Load Apply Wettable Powder Using a Low Pressure Handwand (2012 Residential SOPs)

5. Daily Dose = [Amount ai Handled (lb) * Unit Exposure (mg/lb ai)]/ Body Weight (80 kg)

6. Inhalation MOE = HED (0.059 mg/kg/day) / Daily Dose (mg/kg/day)
Page 32 of 75

There is the potential for post-application exposure for individuals exposed as a result of being in 

an environment that has been previously treated with azoxystrobin. The quantitative 

exposure/risk assessment for residential post-application exposures has been updated here for the 

purposes of the aggregate risk assessment because the inhalation POD has changed since the 

previous full assessment of all the existing residential uses (K. Rury, D394287, 03/30/2012). 

The quantitative exposure/risk assessment for residential post-application exposures is based on 

the scenarios listed in Table 6.2.1. The lifestages selected for each post-application scenario are 

based on an analysis provided as an Appendix in the 2012 Residential SOPs7. While not the only 

lifestage potentially exposed for these post-application scenarios, the lifestage that is included in 

the quantitative assessment is health protective for the exposures and risk estimates for any other 

potentially exposed lifestage. There was no dermal hazard identified for azoxystrobin; therefore 

only incidental oral and inhalation post-application exposures were assessed for the residential 

uses of azoxystrobin.

A series of assumptions and exposure factors served as the basis for completing the residential 

post-application risk assessment. Each assumption and factor is detailed in the 2012 Residential 

SOPsError! Bookmark not defined..

Residential exposure is expected to be short-term in duration. Intermediate-term exposures are 

not likely because of the intermittent nature of applications by homeowners. Granular ingestion 

following treatment of turf is considered episodic in duration. Because the soil half-life is 

relatively short, intermediate-term exposures are not expected. 

The incidental oral scenarios (i.e., hand-to-mouth and object-to-mouth) should be considered 

inter-related and it is likely that they occur interspersed amongst each other across time. 

Combining these scenarios with the dermal exposure scenario would be overly-conservative 

because of the conservative nature of each individual assessment. This assessment should be 

considered a protective estimate of potential post-application exposure for children 1 to < 2 years 

old. Ingestion of granules is considered an episodic event and not a routine behavior. Because 

HED does not believe that this would occur on a regular basis, our concern for human health is 

related to acute poisoning rather than short-term residue exposure. Therefore, an acute dietary 

dose is used to estimate exposure and risk resulting from episodic ingestion of granules. 

The registered residential uses of azoxystrobin do not result in any risks of concern for postapplication incidental oral exposures. 

Table 6.2.1. Residential Post-application Non-cancer Exposure and Risk Estimates for the Conventional Uses of 

Azoxystrobin.

Lifestage

Post-application Exposure Scenario Application Rate1 Dose (mg/kg/day)2 MOEs3

Use Site Route of Exposure

Children 1 to 

< 2 years old

Turf (Liquid/Sprays)

Hand-to-Mouth

0.99 lb ai/A

0.0151 2,300

Object-to-Mouth 0.0046 76,000

Soil Ingestion 0.000034 1,00,000

Turf (Granular) Hand-to-Mouth 0.95 lb ai/A 0.0014 24,000

 

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Table 6.2.1. Residential Post-application Non-cancer Exposure and Risk Estimates for the Conventional Uses of 

Azoxystrobin.

Lifestage

Post-application Exposure Scenario Application Rate1 Dose (mg/kg/day)2 MOEs3

Use Site Route of Exposure

Object-to-Mouth 0.000088 400,000

Soil Ingestion 0.000032 1,100,000

Granular Ingestion 0.31% ai 0.085 2,400

1. Based on registered or proposed labels (Reg. No. 89442-21, and 100-1275).

2. Dose (mg/kg/day) algorithms provided in 2012 Residential SOPs (http://www2.epa.gov/pesticide-science-and-assessing-pesticiderisks/standard-operating-procedures-residential-pesticide).

3. MOE = POD (mg/kg/day) ÷ Dose (mg/kg/day). Incidental oral POD = 35 mg/kg/day where LOC = 100 ; Incidental episodic oral POD = 200 

mg/kg/day, where LOC = 300. 

6.2.2 Residential Post-Application Exposure/Risk Estimates –

Antimicrobial Azoxystrobin Uses

There is the potential for residential post-application incidental oral exposures to vinyl flooring 

made from azoxystrobin treated/impregnated vinyl and plastic toys manufactured from 

azoxystrobin treated plastic. There is the potential for residential post-application incidental oral 

and inhalation exposures from indoor mold spray treatment and indoor carpet and hard surface 

treatment for mold. 

Incidental Oral Exposure – Treated Vinyl Flooring 

Vinyl tiles used for flooring can be treated with azoxystrobin during the manufacturing process. 

Therefore, post-application incidental oral exposures to treated/impregnated vinyl flooring may 

occur. Children (1 to < 2 years old) are the index lifestage for this scenario. Because the 

Residential SOPs deal primarily with conventional pesticides that are applied to surfaces, rather 

than antimicrobials that are incorporated into materials, modifications were made to the surface 

residue equations to include an availability factor (AF) of 0.5 percent8to account for the fact that 

only a small portion of the antimicrobial ingredient incorporated into plastic is at the surface and 

available for exposure. 

The MOE for incidental oral hand-to-mouth exposure to azoxystrobin treated vinyl flooring is 

summarized in Table 6.2.2.1. The MOE is 610 and the risk is not of concern. 

Table 6.2.2.1. Incidental Oral Hand to Mouth MOE for Azoxystrobin Treated Vinyl Flooring.

Application Rate

(percent by 

weight)

Surface 

Residue1

(mg/cm2)

Transfer 

Factor

Hand 

Residue2

(mg/cm2)

Exposure3

(mg/day)

Dose4

(mg/kg/day)

Incidental 

Oral MOE5

0.225 0.0044 1.0 0.0044 0.65 0.057 610

1. Surface Residue (SR) = Density (1300 mg/cm3) * Vinyl Thickness (0.3 cm) * Weight Fraction (AR/100) * Availability Factor (0.5/100)

2. Hand Residue (HR) = SR (mg/cm2) * Transfer Factor (1.0)

3. Exposure = HR (mg/cm2) * FM (0.13) * SAH (150 cm2) * ET (2 hr) * NR (4/hr) * [1 – (1-SE (0.48)FHtM (20/hr)/NR(4)]}

4. Dose = Exposure (mg/day) / BW (11 kg)

5. MOE = NOAEL / Dose where the NOAEL is 35 mg/kg/day and the target MOE is 100.

Incidental Oral Exposure – Indoor Spray Antimicrobial Applications 

There is potential for incidental oral exposures for children’s hand-to-mouth contact with carpet 

 

8 The availability factor is based on migration calculations using Fick’s 1st and 2nd laws of diffusion as programmed in the Arthur D. Little 

Polymer Migration Estimation Model (AMEM) model. 
Page 34 of 75

and hard surfaces treated with azoxystrobin mold spray, as well as post-application inhalation 

exposure from indoor applications of surface sprays for adults and children. A series of 

assumptions and exposure factors served as the basis for completing the residential postapplication risk assessment. Each assumption, factor, and algorithm is detailed in the 2012 

Residential SOPs9. The MOEs for post application exposure to the indoor uses of azoxystrobin 

are summarized in Table 6.2.2.2. Incidental oral exposures were not combined from both treated 

hard surfaces and carpets because of the already conservative assumptions inherent in the 

assessment. When assessing individual short-term residential post-application exposure 

scenarios, EPA assumes exposure occurs to zero-day residues (i.e., day of application residues) 

day after day, for the same amount of time every day (i.e., no day to day variation). hese 

exposure estimates are then compared to points of departure that are typically based on weeks of 

dosing in test animals. For azoxystrobin, the short-term risk assessment has the additional 

conservatism of basing the level of concern for short-term exposure (30-days) on a toxicity study 

involving continuous exposure over 10 weeks for parental animals; and at least 21 days for pups 

while also being exposed in utero.

Table 6.2.2.2. Residential Post-application Non-cancer Exposure and Risk Estimates for the Indoor 

Antimicrobial Uses of Azoxystrobin.

Lifestage

Post-application Exposure Scenario Application Rate1 Dose (mg/kg/day)2 MOEs

(LOC = 100)3 Use Site Route of Exposure

Adult Indoor Mold Surface Directed 

Sprays Inhalation 0.0078 lb ai/gal 0.0000000023 8,800,000

Children 1 to 

< 2 years old

Indoor Mold Surface Directed 

Sprays Inhalation

0.0078 lb ai/gal or 

0.000031 lb ai/ft2

0.0000000084 2,400,000

Indoor Surface Directed Sprays –

Carpets Hand-to-Mouth 0.0902 390

Indoor Surface Directed Sprays –

Hard Surfaces Hand-to-Mouth 0.0301 1,100

Indoor Surface Directed Sprays –

Carpets Object-to-Mouth 0.013 2,700

Indoor Surface Directed Sprays –

Hard Surfaces Object-to-Mouth 0.0087 4,000

1. Based on registered or proposed labels (Reg. No. 89442-21, 100-1275, and 100-1093).

2. Dose (mg/kg/day) algorithms provided in 2012 Residential SOPs (http://www2.epa.gov/pesticide-science-and-assessing-pesticiderisks/standard-operating-procedures-residential-pesticide).

3. MOE = POD (mg/kg/day) ÷ Dose (mg/kg/day). Incidental oral POD = 35 mg/kg/day, inhalation HED (0.02 mg/kg/day). 

Incidental Oral Exposure – Exposure from Plastic Toys 

Plastics and polymers can be treated with an azoxystrobin during production and these plastics 

and polymers can be subsequently used to manufacture toys. Therefore, unless the label 

specifically prohibits use in plastics and polymers used to manufacture toys, it is assumed 

children’s post application incidental oral exposures to treated toys may occur. It is assumed that 

not all plastic toys are treated with azoxystrobin and the toys that are treated will not be used 

every day, therefore, exposure would occur intermittently. Thus, only short-term exposures 

durations were assessed. Children (1 to < 2 years old) are the index lifestage for this scenario.

Each assumption, factor, and algorithm is detailed in the 2012 Residential SOPs10. The MOE for 

incidental oral hand to mouth exposure to azoxystrobin treated toys is summarized in Table 

 

9 http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-procedures-residentialpesticide

10 http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-procedures-residentialpesticide
Page 35 of 75

6.2.2.3. The MOE is 2,500 and the risk is not of concern. 

Table 6.2.2.3. Incidental Oral Object to Mouth MOE for Azoxystrobin Treated Toys.

Weight Fraction Surface 

Residue1

(mg/cm2)

Object Residue2

(mg/cm2)

Exposure3

(mg/day)

Dose4

(mg/kg/day)

Incidental Oral 

MOE5

(LOC = 100)

0.00225 0.0011 0.0011 0.16 0.014 2,500

1. Surface Residue (SR) = WF (0.00225) * Toy Weight (50 grams) * 1000 mg/gm * Availability Factor (0.5/100)

 Toy Surface Area (500 cm2)

2. Object Residue (OR) = SR (mg/cm2) * Transfer Factor (1.0)

3. Exposure = OR (mg/cm2) * Surface Area Mouthed (10 cm2) * Exposure Time (4 hr) * NR (4/hr) * [1 – (1-SE (0.48)FHtM (14/hr)/NR(4)]}

4. Dose = Exposure (mg/day) / BW (11 kg)

5. MOE = NOAEL / Dose where the NOAEL is 35 mg/kg/day and the target MOE is 100.

6.3 Residential Risk Estimates for Use in Aggregate Assessment 

Table 6.3 reflects the residential risk estimates that are recommended for use in the aggregate 

assessment for azoxystrobin. An adult aggregate assessment including residential handler 

inhalation exposures has not been conducted because effects seen in the route-specific inhalation 

toxicity study differ from those seen via the oral route; therefore residential exposures will not be 

aggregated with dietary exposures for adults. The recommended residential exposure for use 

in the children 1 to <2 years old aggregate assessment reflects hand-to-mouth incidental 

oral exposures from treated carpets. 

Ingestion of granules is considered an episodic event and not a routine behavior. Because HED 

does not believe that this would occur on a regular basis, our concern for human health is related 

to acute poisoning rather than short-term residue exposure. Therefore, an acute dietary dose is 

used to estimate exposure and risk resulting from episodic ingestion of granules. For these same 

reasons, the episodic ingestion scenario is not recommended for inclusion in the aggregate 

assessment. 

Table 6.3. Recommended Scenarios for the Residential Exposures for the Azoxystrobin Aggregate Assessment.1

Lifestage

Post-application Exposure (mg/kg/day) Residential Post-application 

Total Exposure 

(mg/kg/day)2

Residential Postapplication MOE3

Inhalation Oral

Short-Term

Child 1 to 

<2 years old N/A 

0.0902

(Hand-to-Mouth exposure from treated 

carpets)

0.0902 390

1. N/A = not applicable. Children handler exposures are not expected. For children 1 to < 2 years old, total residential 

exposure represents high-end post-application incidental oral exposure (Tables 5.2.2.2). 

2. Post-application exposure represents high-end or incidental oral exposure for the relevant exposure duration.

3. Total MOE = NOAEL (35 mg/kg/day) ÷ (Incidental Oral Exposure). 

Since the estimated residential turf post-application exposure for residential turf using default 

TTR values for azoxystrobin is minimal in comparison to the level of concern (i.e., the calculated 

MOE is greater than 10 times higher than the level of concern, MOE = 2,300 compared to the 

LOC of 100), EPA is recommending that the 40CFR TTR data requirement is not needed. In 

this instance, it is unlikely that chemical-specific TTR data would be needed to further refine 

exposure assessments or would add appreciably to our general understanding of the availability 

of turf transferable pesticide residues.
Page 36 of 75

Because no dermal hazard was identified for azoxystrobin, a residential post-application 

assessment on ornamentals was not conducted; therefore a DFR study is not needed for 

azoxystrobin at this time. 

6.4 Residential Bystander Post-Application Exposure 

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

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

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

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

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

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

subsequent Volatilization Screening Analysis 

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

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

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

Per the Residential SOPs, a quantitative residential post-application inhalation exposure 

assessment was performed in the residential post-application section of the ORE chapter.

7.0 Non-Occupational Spray Drift Exposure and Risk Estimates 

Off-target movement of pesticides can occur via many types of pathways and it is governed by a 

variety of factors. Sprays that are released and do not deposit in the application area end up offtarget and can lead to exposures to those it may directly contact. They can also deposit on 

surfaces where contact with residues can eventually lead to indirect exposures (e.g., children 

playing on lawns where residues have deposited next to treated fields). The potential risk 

estimates from these residues can be calculated using drift modeling coupled with methods 

employed for residential risk assessments for turf products.

The approach to be used for quantitatively incorporating spray drift into risk assessment is based 

on a premise of compliant applications which, by definition, should not result in direct exposures 

to individuals because of existing label language and other regulatory requirements intended to 

prevent them.11 Direct exposures would include inhalation of the spray plume or being sprayed 

directly. Rather, the exposures addressed here are thought to occur indirectly through contact 

with impacted areas, such as residential lawns, when compliant applications are conducted. 

Given this premise, exposures for children (1 to 2 years old) and adults who have contact with 

turf where residues are assumed to have deposited via spray drift thus resulting in an indirect 

exposure are the focus of this analysis analogous to how exposures to turf products are 

considered in risk assessment. 

Several azoxystrobin products have existing labels for use on turf, thus it was considered 

whether the risk assessment for that use may be considered protective of any type of exposure 

 

11 This approach is consistent with the requirements of the EPA’s Worker Protection Standard which, 

when included on all labels, precludes direct exposure pathways.
Page 37 of 75

that would be associated with spray drift. It should be noted that the registered residential uses 

on turf result in exposure greater than potential exposure from spray drift; therefore, no new 

residential assessment needs to be completed. If the maximum application rate on crops adjusted 

by the amount of drift expected is less than or equal to existing turf application rates, the existing 

turf assessment is considered protective of spray drift exposure. The currently registered

maximum single application rate of azoxystrobin is 0.33 lb ai/A. The highest degree of spray 

drift noted for any application method immediately adjacent to a treated field (Tier 1 output from 

the aerial application using fine to medium spray quality) results in a deposition fraction of 0.26 

of the application rate. A quantitative spray drift assessment for azoxystrobin is not required 

because the maximum application rate to a crop/target site multiplied by the adjustment factor 

for drift of 0.26 is less than the maximum direct spray residential turf application rate of 0.99 lb 

ai/A12 for any azoxystrobin products. The turf post-application MOEs have been previously 

assessed and are based on the revised SOPs for Residential Exposure Assessment (i.e., see above 

in Section 6.2.1). 

8.0 Aggregate Exposure/Risk Characterization

HED must consider and aggregate (add) pesticide exposures and risks from three major sources: 

food, drinking water, and residential exposures. In an aggregate assessment, exposures from 

relevant sources are added together and compared to quantitative estimates of hazard (e.g. a 

NOAEL or PAD), or the risks themselves can be aggregated. When aggregating exposures and 

risks from various sources, HED considers both the route and duration of exposure. For 

azoxystrobin, potential exposures from food, drinking water and residential scenarios were 

aggregated. 

This assessment has utilized the Residential Standard Operating Procedures (SOPs) implemented 

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

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 

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

exposure to azoxystrobin in food and drinking water, are below the Agency’s LOC. The food 

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

40% for the most highly exposed subgroup, children 1-2 years old. 

 

12 0.33 lb ai/A x 0.26 ≤ 0.99 lb ai/A
Page 38 of 75

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 

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

incidental oral (primary) routes. 

The effects seen in the inhalation toxicity study differ than those seen in the oral toxicity studies. 

Therefore, inhalation exposures and oral exposures are not aggregated for adults and children

and the adult short-term aggregate risks are equivalent to dietary exposures only (See Section 

5.0). 

The most conservative scenario was chosen to assess aggregate risks for children 1 to < 2 years 

old (hand-to-mouth exposure from carpets for children 1 to < 2 years old) with dietary exposures. 

For a description of the residential exposure scenarios considered in the aggregate assessment,

see Section 6.3.

The aggregate MOE for children 1 to < 2 years old, including incidental oral exposures from 

treated carpets, is 300, which indicates that aggregate exposure and risk is greater than HED’s 

LOC (MOE<100) and not of concern. Further refinement using additional % CT estimates or 

more refined EDWCs may need to be incorporated in future assessments. 

Table 7.2. Short- and Intermediate Term Aggregate Risk Calculations.

Population

Short- and Intermediate-Term Scenarios

NOAEL 

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food and 

Water 

Exposure 

mg/kg/day

Residential 

Exposure 

mg/kg/day3

Total 

Exposure 

mg/kg/day4

Aggregate 

MOE (food, 

water, and 

residential)5

Child 35 100 0.35 0.027728 0.0902 0.12 300

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

2. Maximum Allowable Exposure (mg/kg/day) = NOAEL (35 mg/kg/day)/LOC (100). 

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

6.3. 

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

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

7.3 Intermediate-Term Aggregate Risk

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

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

equivalent to the chronic dietary exposure estimate. 

7.4 Chronic Aggregate Risk

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

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

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

exposure assessment. 
Page 39 of 75

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. 

9.0 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 Registration Review, 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://www2.epa.gov/pesticide-science-and-assessing-pesticiderisks/cumulative-assessment-risk-pesticides/

10.0 Occupational Exposure/Risk Characterization

10.1 Short- and Intermediate-Term Handler Risk – Conventional Azoxystrobin 

Uses

HED uses the term handlers to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct job functions or tasks related to 

applications and exposures can vary depending on the specifics of each task. Job requirements 

(amount of chemical used in each application), the kinds of equipment used, the target being 

treated, and the level of protection used by a handler can cause exposure levels to differ in a 

manner specific to each application event. 

No chemical-specific data for assessing human exposures during pesticide handling activities 

were submitted to the Agency for azoxystrobin. It is the policy of HED to use the best available 

data to assess handler exposure. Sources of generic handler data, used as surrogate data in the 

absence of chemical-specific data, include PHED 1.1, the Policy 14 for Seed Treatment, AHETF 

database, the Outdoor Residential Exposure Task Force (ORETF) database, the Post-Harvest 

SOP, or other registrant-submitted occupational exposure studies. Some of these data are 

proprietary (e.g., AHETF data), and subject to the data protection provisions of FIFRA. 

For azoxystrobin, based on the existing uses, both short- and intermediate-term exposures are 

expected for occupational handlers because it could be applied multiple times per season to many 

registered crops. However, the occupational inhalation POD is applicable to both durations; 

therefore the assessment is protective of both short- and intermediate-term exposures. 

The registered azoxystrobin labels require baseline attire (long sleeved shirts, long pants, shoes, 

and socks) and in addition to PPE including chemical resistant gloves; and in some cases, 
Page 40 of 75

protective eyewear, a respirator, or double layer clothing. Only liquid formulation labels that are 

co-formulated with other active ingredients require respirators, and no dry flowable products 

require the use of respirators when handling azoxystrobin

There are some occupational handler risk estimates of concern for the registered uses of 

azoxystrobin at baseline, PPE, and engineering control mitigation. The level of concern (LOC) 

for occupational inhalation risk estimates is an MOE of 300. At baseline, occupational handler 

inhalation MOEs ranged from 1.1 to 50,000. The quantitative exposure/risk assessment 

developed for occupational handlers is based on the scenarios listed in Appendix D.

The following scenarios are of concern with baseline PPE (no respirator): 

 Mixing/loading dry flowables for aerial, airblast, groundboom, and chemigation 

application to all registered crops at maximum registered application rates; 

 Mixing/loading granules for aerial application to sod; 

 Mixing/loading granules for tractor-drawn spreader applications to sod and golf course 

fairways, greens, and tees (all three combined). 

 Mixing/loading liquids for aerial application to orchards/vineyards, sod, typical field 

crops, and high acreage13 field crops at maximum registered application rates; 

 Mixing/loading liquids for chemigation application to orchards/vineyards, sod, typical 

field crops, high acreage field crops; 

 Mixing/loading liquids for groundboom application to sod and high acreage field crops; 

 Applying sprays with airblast application equipment to nursery ornamentals and 

orchards/vineyards; 

 Applying sprays with groundboom application equipment to sod; golf course fairways, 

tees, and greens; typical field crops; and high acreage field crops; 

 Applying granules with aerial application equipment to sod; 

 Applying granules with a tractor-drawn spreader to sod, and golf course fairways, greens, 

and tees; 

 Flagging for aerial application to sod during liquid and granular applications; 

 Mixing/loading/applying dry flowable or liquid formulations with a backpack sprayer to 

orchard/vineyards, Christmas tree farms, and nursery ornamentals; 

 Mixing/loading/applying dry flowable or liquid formulations using a manually 

pressurized handwand to Christmas tree farms, nursery ornamentals, and landscaping; 

 Mixing/loading/applying dry flowable or liquid formulations using a mechanically 

pressurized handwand to orchard/vineyards, Christmas tree farms, nursery ornamentals, 

golf courses, landscaping, and typical field crops; 

 Mixing/loading/applying liquids with a manually pressurized handwand to greenhouse 

ornamentals; 

 

13 Registered azoxystrobin use sites include numerous agricultural commodities. In the assessment, “typical field 

crops” include commodities such as artichokes, berries, Brassica, bulbs, cucurbits, fruiting vegetables, and leafy 

vegetables. The acres treated assumptions are less than for “high acreage field crops” which are commodities grown 

over larger areas, such as cereal grains, rice, soybeans, and sugarcane. 
Page 41 of 75

 Mixing/loading/applying liquids with a mechanically pressurized handwand to 

orchards/vineyards, Christmas tree farms, nursery ornamentals, greenhouse ornamentals, 

landscaping, and typical field crops; 

 Loading/applying granule formulations with a rotary spreader to golf courses; 

 Mixing/loading for post-harvest treatments in a closed system to citrus; 

 Mixing/loading dry flowable formulations in an automated system for post-harvest 

treatment of bananas, 

 Mixing/loading liquids in an automated system for post-harvest treatment for citrus; 

 Applying direct post-harvest sprays using a mechanically pressurized handgun to citrus 

and bananas; 

 Loading/applying, sewing, bagging, and multiple activities for numerous liquid seed 

treatment uses of azoxystrobin; 

 Planting treated barley, legume vegetable, peanut, potato, triticale, tuberous and corm 

vegetable, turf, and wheat seeds with liquid formulations of azoxystrobin; 

 Loading/applying, sewing, bagging, multiple activities for dust seed treatment 

applications to peanuts; 

 Planting peanut seeds treated with dust formulations; 

 Loading/applying, sewing, bagging, and multiple activities for cotton dry flowable seed 

treatment uses of azoxystrobin; and

 Sorting and packing following post-harvest treatment of citrus and bananas.

The following scenarios are of concern with maximum available personal protective equipment

or engineering controls: 

 Mixing/loading dry flowable formulations for aerial or chemigation application to sod 

and high acreage field crops; 

 Mixing/loading granule formulations for aerial application to sod; 

 Mixing/loading/applying dry flowable formulations for backpack sprayer application to 

landscaping; 

 Mixing/loading/applying dry flowable formulations for mechanically pressurized 

handgun applications to golf courses, landscaping, and typical field crops. 

 Mixing/loading/applying liquids for backpack application to landscaping and turf; 

 Mixing/loading/applying liquids for mechanically pressurized handgun applications to 

typical field crops and greenhouse ornamentals; 

 Mixing/loading liquids for post-harvest treatment of citrus in a closed automated system; 

 Mixing/loading liquids for post-harvest treatment of citrus in an open automated system; 

 Mixing/loading/applying liquids for post-harvest treatment of citrus using a mechanically 

pressurized handgun. 

 Loading/applying liquid formulation to sunflower seeds; 

 Sewing bags of treated sunflower seeds following liquid seed treatment; 

 Multiple activities following/during liquid seed treatment for sunflower seed treatment; 

 Planting potato, tuberous and corm vegetable, and turf seeds following liquid seed 

treatment; 

 Loading/applying, sewing, bagging, and multiple activities following/during dust 

treatment of peanut seeds; 
Page 42 of 75

 Loading/applying, sewing, bagging, and multiple activities following dry flowable 

formulation treatment of cotton seeds. 

The Agency matches quantitative occupational exposure assessment with appropriate 

characterization of exposure potential. While HED presents quantitative risk estimates for human 

flaggers where appropriate, agricultural aviation has changed dramatically over the past two 

decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of 

their membership, the use of GPS for swath guidance in agricultural aviation has grown steadily 

from the mid 1990’s. Over the same time period, the use of human flaggers for aerial pesticide 

applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent 

(2012) NAAA survey. The Agency will continue to monitor all available information sources to 

best assess and characterize the exposure potential for human flaggers in agricultural aerial 

applications.

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

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

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

and socks); per the Agency’s Worker Protection Standard stipulations for engineering controls, 

pilots are not required to wear protective gloves for the duration of the application. With this 

level of protection, there are currently no risk estimates of concern for applicators, except for 

aerial application of granules to sod.

10.2 Short- and Intermediate-Term Handler Risk – Antimicrobial Uses 

There is the potential for occupational handler inhalation exposure during the use of 

azoxystrobin as a material preservative in interior and exterior paints, paper, wallboard, ceiling 

tiles, caulks, sealants, adhesives, binders, non-apparel textiles and plastics. The exposure 

duration is assumed to be primarily intermediate to long term because these uses occur in 

manufacturing plants that operate on a year round basis. 

There is also a potential for occupational handler exposure during the application of azoxystrobin 

preserved paints using airless sprayers, brushes and rollers. These exposures are anticipated to 

occur on a short to intermediate term basis because several other preservatives besides 

azoxystrobin are used in paints.

The occupational handler risk estimate (i.e. MOE) for the material preservation uses of 

azoxystrobin is summarized in Appendix D (Table D.7). The MOE is less than the LOC of 300 

(i.e. the target MOE) for paint manufacturing without respirators which means that the risk is of 

concern. If a PF-10 elastomeric half face respirator is worn, the MOE is increased to 300 and is 

no longer of concern.

The MOEs are also of concern for both airless spray and brush/roller paint application. These 

risks cannot be mitigated with respiratory protection because preserved paints are not EPA 

registered pesticide products and thus do not have labels that could include PPE requirements. 

10.3 Occupational Post-Application Exposure/Risk Estimates
Page 43 of 75

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure.

10.3.1 Occupational Post-Application Inhalation Exposure/Risk Estimates 

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

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

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

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

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

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

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

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

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

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

required for azoxystrobin.

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

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

Agency will continue to identify the need for and, subsequently, the way to incorporate 

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

The Worker Protection Standard for Agricultural Pesticides contains requirements for protecting 

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

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

applications)]

Occupational Post-Application Inhalation Exposure Data and Assumptions

Although the post-application exposures due to agricultural applications has not been 

quantitatively evaluated, there is the potential for occupational post-application inhalation 

exposures in post-harvest treatment facilities. During automated treatments, dermal and 

inhalation exposure is anticipated for workers performing sorting and packing tasks. Since the 

workers experience exposure following the treatment, this is technically “post-application” 

exposure; however, unlike other post-application activities (e.g., harvesting, scouting, etc.), this 

treatment is not governed by the Worker Protection Standard (WPS) and potential re-entry 

intervals (REIs). Additionally, for workers in the warehouse or packaging facility not directly 

involved in the automated treatment process, there is potential for indirect inhalation exposure. 
Page 44 of 75

Exposures for these various scenarios are assessed using HED ExpoSAC Policy/Guidance

“Assessment of Occupational Exposure for Post-Harvest Commodity Pesticide Treatments” (M. 

Crowley, 23-MAR-2012). A series of assumptions and exposure factors served as the basis for 

completing the occupational post-application risk assessment. Each assumption and factor is 

detailed below on an individual basis. 

Exposure Duration: HED classifies exposures from 1 to 30 days as short-term and exposures 30 

days to six months as intermediate-term. Exposure duration is determined by many things, 

including the exposed population, the use site, the pest pressure triggering the use of the 

pesticide, and the cultural practices surrounding that use site. For most agricultural uses, it is 

reasonable to believe that occupational post-application workers will not apply the same 

chemical every day for more than a one-month time frame; however, there may be a large 

agribusiness and/or commercial applicators who may apply a product over a period of weeks 

(e.g., completing multiple applications for multiple clients within a region). 

For azoxystrobin, based on the existing uses, both short- and intermediate-term exposures are 

expected for occupational handlers in post-harvest facilities because it could be applied yearround to the registered crops. Additionally, the occupational inhalation POD is applicable to 

both durations; therefore the assessment is protective of both short- and intermediate-term 

exposures. Long-term exposures are not expected because exposures resulting from post-harvest 

uses are likely a series of short- or intermediate-term exposures, rather than continuous long-term 

exposure duration just to azoxystrobin. 

Exposure Time: The average occupational workday is assumed to be 8 hours. 

Occupational Post-application Non-Cancer Inhalation Risk Estimates

There are some occupational post-application inhalation risk estimates of concern for the 

registered post-harvest uses of azoxystrobin at baseline and maximum PPE mitigation. The LOC 

for occupational inhalation risk estimates is an MOE of 300. At baseline, occupational postapplication inhalation MOEs for the post-harvest uses of azoxystrobin ranged from 1.5 to 

5,200,000 for sorters/packers and from 32 to 1,200,000 for indirect inhalation exposures 

(Appendix D, Tables D.8 and D.9). 

10.3.2 Occupational Post-Application Dermal Exposure/Risk Estimates

An occupational post-application dermal assessment was not completed for any use pattern 

because no dermal hazard was identified in the azoxystrobin toxicity database that is suitable for 

risk assessment purposes. 

Restricted Entry Interval

For Azoxystrobin Products with a >12 Hour REI

Without a dermal toxicity endpoint that can used to assess dermal risk, re-entry intervals are 

assigned on the basis of acute toxicity categorization. Azoxystrobin is classified as Toxicity 

Category III via the dermal route and Toxicity Category IV for skin irritation potential. It is not 
Page 45 of 75

a skin sensitizer. Short- and intermediate-term post-application risk estimates were not a concern 

on day 0 (12 hours following application) for all post-application activities. Under 40 CFR 

156.208 (c) (2), ai’s classified as Acute III or IV for acute dermal, eye irritation and primary skin 

irritation are assigned a 12-hour REI. Therefore, the [156 subpart K] Worker Protection 

Statement interim REI of 12 hours is adequate to protect agricultural workers from postapplication exposures to azoxystrobin. 

For Azoxystrobin Products with a 4-hour REI

Based on the acute toxicity categories, the Worker Protection Standard (WPS) REIs for

azoxystrobin, is 12-hours. REIs may be reduced if registrant-submitted 95-3 package has been 

approved and 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 WPS 

Interim REIs for Certain Low Risk Pesticides]14. Based only on the acute toxicity categories for

azoxystrobin, HED recommends a 12-hour REI.

11.0 Public Health and Pesticide Epidemiology Data

Both the OPP Incident Data System (IDS) and the Centers for Disease Control and 

Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event 

Notification System for Occupational Risk-Pesticides (SENSOR) databases were consulted for 

pesticide incident data on the active ingredient azoxystrobin. In addition, findings from the 

Agricultural Health Study (AHS) were reviewed. Azoxystrobin is not included in the AHS, and 

therefore this study does not provide information for this report. The current IDS analysis from 

January 1, 2010 through May 27, 2015, shows 4 moderate severity incidents reported involving 

the single active ingredient, azoxystrobin, and 29 additional incidents involving multiple 

chemicals in Main IDS. There were 40 minor severity incidents reported to Aggregate IDS. 

Dermal symptoms were reported most often which included redness, rash and burning. There 29 

additional incident reported to Main IDS, involving azoxystrobin and other active ingredients. 

The query of SENSOR-Pesticides 1998-2011 identifies 51 total cases involving azoxystrobin and 

13 cases involve a single ai. Twelve of the 13 cases were low in severity and one was moderate 

in severity. One event involved four cases, agricultural workers in a field that became ill after 

being directly sprayed by an aerial applicator who was making an application to a nearby field 

and then failed to turn of the spray while making a turn. Another event involved a father and 

young daughter who were made ill from drift15 following an aerial application to a nearby potato 

field. Labels of products falling under the jurisdiction of the WPS are directed to not allow 

direct application or drift to contact workers and other people. These two events appear to 

represent use inconsistent with the label, i.e., misuse. 

Based on the relatively low frequency of incidents reported to both IDS and SENSOR-Pesticides, 

there does not appear to be a concern at this time. The Agency will continue to monitor the 

incident data and if a concern is triggered, additional analysis will be conducted.

 

14 Available: http://www2.epa.gov/pesticide-registration/prn-95-3-reduction-worker-protection-standard-wpsinterim-restricted-entry

15 SENSOR-Pesticides defines drift as “off target movement of a pesticide” which includes volatilization.
Page 46 of 75

12.0 References

G. Dannan. 09/25/2000; HED Doc No. 014329. AZOXYSTROBIN - Report of the Hazard 

Identification Assessment Review Committee. 

E. Evans; 12/02/2015; D430445. Azoxystrobin: Tier I Review of Human Incidents for Draft 

Risk Assessment

S. Funk. 11/12/2014, D423334 and D423718. Azoxystrobin. Petition for the Establishment of 

Permanent Tolerances on Imported Pear, Imported Tea, and Imported Coffee. Petition for the 

Establishment of Permanent Tolerance on Ti Palm, and for Crop Group Conversions for Stone 

Fruit Group 12-12 and Tree Nut Group 14-12. Summary of Analytical Chemistry and Residue 

Data. D423334 and D423718. 11/12/2014. 

S. Funk. 10/29/2014, D423337 and D423720. Azoxystrobin: Acute and Chronic Aggregate 

Dietary (Food and Drinking Water) Exposure and Risk Assessments for Section 3 Petitions for 

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

Establishment of Tolerances and Registration for Use on Ti Palm Roots and Leaves 

(PP#4E8319) and Crop Group Conversions for Stone Fruit Group 12-12 and Tree Nut Group 14-

12. 

J. Leshin; TXR#0057242. Azoxystrobin - Report of the Hazard and Science Policy Council 

(HASPOC) Meeting of September 3, 2015: Recommendations on the Need for a Subchronic 

Inhalation Toxicity study. 

J. Leshin, 11/13/2014, TXR#0057071. Azoxystrobin: Summary of the Hazard and Science 

Policy Council (HASPOC): Recommendations on the Requirement of an Immunotoxicity Study. 

K. Rury. 04/07/2015, D423691, D418374, Azoxystrobin Human Health Aggregate Risk

Assessment for Permanent Tolerances on Imported Asian Pear, Imported Tea, and Imported 

Coffee; Establishment of Permanent Tolerances on Ti Palm and for Crop Group Conversions for 

Stone Fruits Group 12-12 and Tree Nut Group 14-12 Crop Groups. 

K. Rury. 12/17/2014, D418012, D423847, Azoxystrobin. Occupational and Residential 

Exposure Assessment for Proposed Uses on Ti Palm, and on Ornamentals and Vegetable 

Transplants Grown Outdoors and in Greenhouses. This assessment also includes updates to the 

Stone Fruit Group 12-12 and Tree Nut Group 14-12 Crop Groups.

K. Rury. 12/4/2015, D430444. Azoxystrobin. Draft Occupational and Residential Registration 

Review Risk Assessment for the Existing Uses of Azoxystrobin. 

I. Abdel-Saheb. 09/11/2014, D422726. Drinking Water Exposure Assessment for new use of 

Azoxystrobin on Ornamental Plants and Vegetable Transplants. 

B. Tarplee and J. Rowland, HED Doc. No. 012844, 09/03/1998
Page 47 of 75

W. Wassell. 12/30/1998, D251683. HED Metabolism Assessment Review Committee Decision 

Memo. 

 
Page 48 of 75

Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.500) for food uses for azoxystrobin are below. Use of the new guideline numbers 

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

Study

Technical

Required Satisfied

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

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

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

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

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

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

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

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

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

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

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

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

yes

yes

yes

no

CR1

yes

yes

yes

no

no*

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

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

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

yes

yes

yes

yes

yes

yes

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

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

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

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

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

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

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

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

870.5375 Mutagenicity—Structural Chromosomal Aberrations...

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

yes

yes

yes

yes

yes

yes

yes

yes

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

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

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

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

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

no

no

yes

yes

no

-

-

yes

yes

no

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

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

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

yes

no

yes

yes

yes

Not Required**

Special Studies for Ocular Effects

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

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

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

yes

no

yes

-

-

-

1CR = Conditionally Required

* A subchronic inhalation toxicity study with the TGAI is recommended (TXR#0057242)

** The immunotoxicity study is not required (TXR#0057071)
Page 49 of 75

A.2 Toxicity Profiles

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

Guideline

No. Study Type MRID # Results

Toxicity 

Category

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

Females

IV

870.1200 Acute Dermal -

Rat

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

Females

III

870.1300 Acute Inhalation -

Rat

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

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

The combined LC50 was not calculated

due to mortality pattern

III

870.2400 Primary Eye 

Irritation - Rabbit

43678128 Slight to moderate erythema and slight chemosis in 

all rabbits within one hour, but effects resolved 

within 48 hours of treatment.

III

870.2500 Primary Skin 

Irritation - Rabbit

43678130 Very slight erythema and edema that persisted for 

three days on one rabbit and for one hour on 

another.

IV

870.2600 Dermal 

Sensitization -

Guinea Pig

43678132 No erythema or edema were found 38 or 48 hrs 

after challenge with test material.

Not a 

dermal 

sensitizer

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

Study Guideline/Study MRID Results

870.3100

90-Day oral toxicity in rats

43678135 (1992) 

Acceptable/guideline

0, 200, 2000, 4000 ppm

M: 0, 20.4, 211.0, 443.8 

mg/kg/day

F: 0, 22.4, 223.0, 448.6 

mg/kg/day

NOAEL = 20 mg/kg/day

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

gain in both sexes, clinical observations of distended 

abdomens and reduced body size, and clinical 

chemistry findings attributable to reduced nutritional 

status.

870.3150

90-Day oral toxicity in 

dogs

43678136 (1993)

Acceptable/guideline

M & F: 0, 10, 50, 250 

mg/kg/day 

NOAEL = 50 mg/kg/day

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

clinical observations and clinical chemistry 

alterations indicative of effects on liver/biliary 

function in both sexes.

870.3200

21-Day dermal toxicity in 

rats

43678137 (1994)

Acceptable/guideline

M & F: 0, 200, 500, 1000

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

LOAEL > 1000 mg/kg/day.

870.3465

28-Day inhalation toxicity 

in rats (SC formulation: 

7.79% a.i.)

49335202 (main study)

49335201 (preliminary-5-

day study

Acceptable/non-guideline

0, 49, 144, & 455 μg/L 

(formulation )

0, 3.8, 11.2, 36.4 μg/L (a.i.) 

NOAEL = 3.8 μg/L

LOAEL = 11.2 μg/L based on the histopathology 

findings of metaplasia in the larynx and nasal cavity 

with increased severity of effects (atrophy of 

ventrolateral respiratory epithelium and increased 

incidence of macrophages in the lung) seen in the 

next higher concentration (36.4 μg/L).

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
Page 50 of 75

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

Study Guideline/Study MRID Results

LOAEL > 100 mg/kg/day.

870.3700b

Prenatal developmental in 

rabbits

44058701 (1995)

Acceptable/guideline

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

Maternal NOAEL = 150 mg/kg/day

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

weight gain.

Developmental NOAEL = 500 mg/kg/day

LOAEL > 500 mg/kg/day.

870.3800

Reproduction and fertility 

effects in rats

43678144 (1994)

Acceptable/guideline

0, 60, 300, 1500 ppm

M: 0, 6.4, 32.3, 165.4 

mg/kg/day

F: 0, 6.8, 33.8, 175.0 

mg/kg/day

Parental/Systemic NOAEL = 32 mg/kg/day

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

weight, reduced food consumption, and increased 

adjusted liver weights in both sexes in addition to 

gross and histopathologic lesions of the bile duct and 

liver in males.

Reproductive NOAEL = 165 mg/kg/day

LOAEL > 165 mg/kg/day.

Offspring NOAEL = 32 mg/kg/day

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

body weight and increased adjusted (for body 

weight) liver weights.

870.4100

Chronic toxicity in dogs

43678140 (1994)

Acceptable/guideline

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

NOAEL = 25 mg/kg/day

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

clinical observations, increased liver weight, and 

clinical chemistry changes indicative of effects on 

liver/biliary function.

870.4200

Carcinogenicity in mice

43678141 (1995)

Acceptable/guideline

0, 50, 300, 2000 ppm

M: 0, 6.2, 37.5, 272.4 

mg/kg/day

F: 0, 8.5, 51.3, 363.3 

mg/kg/day

NOAEL = 38 mg/kg/day

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

weights in both sexes.

There was no evidence of carcinogenicity.

870.4300

Combined Chronic 

toxicity/ Carcinogenicity 

in rats

43678139 (1995)

Acceptable/guideline

0, 60, 300, &1500/750 ppm 

for males (due to excessive 

death the high dose was 

reduced beginning at week 

52-104)

For females: 0, 60, 300,& 

1500 ppm

M: 0, 3.6, 18.2, 82.4 

mg/kg/day

F: 0, 4.5, 22.3, 117.1 

mg/kg/day

NOAEL = 18 mg/kg/day

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

mg/kg/day in females based on reduced body 

weights in both sexes and bile duct lesions in males.

There was no evidence of carcinogenicity.

870.5100

Bacterial reverse gene 

mutation

43668146 (1992)

Acceptable/guideline

100, 200, 500, 1000, 2500, 

5000 μg/plate

Negative in increasing revertant colonies up to 5000 

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

preincubation protocols and Salmonella strains 

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

E. Coli strains WP2P and WP2PuvrA. Cytotoxicity 

and compound precipitation were seen at the high 

dose.

870.5300 43678145 (1993)

Acceptable/guideline

Nonlinear, slight but significant increases in the 

mutation frequency (MF) of mouse lymphoma 

L5178Y TK+/-at 15-60 μg/mL +/-S9. Despite the 
Page 51 of 75

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

Study Guideline/Study MRID Results

Mammalian cell forward 

gene mutation (mouse 

lymphoma cells)

8 to 80 μg/mL in three 

assays

absence of a dose response, increased MFs were 

reproducible; therefore, Azoxystrobin is considered 

positive in this test system. Colony sizing was not 

performed.

870.5375

Cytogenetics chromosomal 

aberration 

43678147 (1992)

Acceptable/guideline

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

The in vitro test in human lymphocytes was positive

for the induction of chromosomal aberrations in both 

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

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

severely cytotoxic (i.e. >16-70% reductions in 

mitotic cells, respectively)

870.5385 

Cytogenetics bone marrow

43678148 (1992)

Acceptable/guideline

5000 

mg/kg

The in vivo mouse bone marrow micronucleus assay 

was negative at 5000 mg/kg when administered once 

by oral gavage. Overt toxicity and depression of 

erythropoiesis seen in addition to cytotoxic effects on 

the target cell in the males. 

870.5550

Other: Unscheduled DNA 

synthesis

43678149 (1992)

Acceptable/guideline

1250 and 2000 mg/kg

The in vivo/in vitro unscheduled DNA synthesis test 

in rat hepatocytes was negative. No toxicity to the 

treated animals or cytotoxic effects on recovered 

hepatocytes up to the limit dose for acute testing 

(2000 mg/kg) when administered once by oral

gavage.

870.6200a

Acute neurotoxicity 

screening battery in rats

43678134 (1994)

Acceptable/guideline

0, 200, 600, 2000 mg/kg

NOAEL < 200 mg/kg/day

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

in both sexes. 

870.6200b

Subchronic neurotoxicity 

screening battery in rats

43678138 (1994)

Acceptable/guideline

0, 100, 500, 2000 ppm

M: 0, 8.0, 38.5, 161 

mg/kg/day 

F: 0, 9.1, 47.9, 201.5 

mg/kg/d

NOAEL = 39 mg/kg/day.

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

weight and food utilization in both sexes.

870.7485

Metabolism and 

pharmacokinetics

43678150

43678151

43678152

43678153

43678154

1 or 100 mg/kg (single 

gavage) or 1 mg/kg (14-

day repeated)

Following oral administration as a single gavage 

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

mg/kg, azoxystrobin was widely distributed with the 

liver and kidneys having the highest concentrations; 

however, less than 0.5% of the administered dose 

was detected in the tissues at seven days postdosing. 

The primary route of excretion was via the feces

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

no apparent sex- or dose-related differences in 

distribution or in the pattern of excretion. In a bile 

duct cannulated single high-dose group, assessment 

of biliary excretion suggested approximately 70% 

absorption with ≈32% of the administered dose 

remaining as parent compound in the gastrointestinal 

tract. Absorbed azoxystrobin appeared to be 

extensively metabolized with minor sex-related 

qualitative and quantitative differences in biliary 

metabolites. A metabolic pathway was proposed 

showing hydrolysis and subsequent glucuronide 

conjugation as the major biotransformation process.

870.7600

Dermal penetration (rat)

43678155 (1994) 2 - 4 % Dermal Absorption 
Page 52 of 75

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

Study Guideline/Study MRID Results

Acceptable/guideline

0.01, 0.1, 0.9, 13.3 mg/kg

Appendix B. Physical/Chemical Properties

Table B. Physicochemical Properties of Technical Grade Azoxystrobin.

Parameter Value Reference

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

3/19/96, J. Garbus pH 6.4

Density 1.25 g/cm3

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

pH 7.0 6.7 mg/L

pH 9.2 5.9 mg/L

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

Octanol 1.4 mg/L

Methanol 20 mg/L

Toluene 55 mg/L

Acetone 86 mg/L

Ethyl Acetate 130 mg/L

Acetonitrile 340 mg/L

Dichloromethane 400 mg/L

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

Dissociation constant, pKa Not dissociable

Octanol/water partition coefficient, 

Log(KOW)

log P = 2.5
Page 53 of 75

Appendix C. Review of Human Research

Human Studies Review

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

intentionally exposed to a pesticide or other chemical. These data, which include studies from 

PHED 1.1; the AHETF database; the AEATF database; ExpoSAC Policy 14 (SOPs for Seed 

Treatment); and the Residential SOPs (Treated Paints, Lawns/Turf, and Indoor Environments); 

and the Post-Harvest SOP; are (1) subject to ethics review pursuant to 40 CFR 26, (2) have 

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

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

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

website16. 

 

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

http://www.epa.gov/pesticides/science/post-app-exposure-data.html
Page 54 of 75

Appendix D. Occupational Exposure/Risk Summary Tables

Table D.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for the Registered Conventional Uses of Azoxystrobin1.

Exposure Scenario Crop or Target1 Maximum

Application Rate2

Inhalation MOE

(LOC = 300)

Baseline PF5 Respirator PF10 Respirator Engineering Control

Mixer/Loader

Mixing/Loading Dry Flowables for Aerial 

Application

Nursery Ornamentals 0.25 lb ai/A 35 180 350 2,300

Orchards/Vineyards 0.25 lb ai/A 6.0 30 60 390

Sod 0.95 lb ai/A 1.6 7.9 16 100

Field Crop, Typical 0.33 lb ai/A 4.6 23 46 300

Field Crop, High Acreage 0.4 lb ai/A 1.1 5.5 11 72

Mixing/Loading Dry Flowables for Airblast 

Application

Nursery Ornamentals 0.25 lb ai/A 110 530 1,100 6,900

Orchards/Vineyards 0.25 lb ai/A 53 260 530 3,400

Mixing/Loading Dry Flowables for Chemigation 

Application

Orchards/Vineyards 0.25 lb ai/A 6.0 30 60 390

Sod 0.95 lb ai/A 1.6 7.9 16 100

Field Crop, Typical 0.33 lb ai/A 4.6 23 46 300

Field Crop, High Acreage 0.4 lb ai/A 3.8 19 38 250

Nursery Ornamentals 0.25 lb ai/A 35 180 350 2,300

Mixing/Loading Dry Flowables for Groundboom 

Application

Golf course (tees and greens) 0.95 lb ai/A 110 560 1,100 7,200

Golf course (fairways, tees, and greens) 0.95 lb ai/A 14 69 140 900

Field-Grown Ornamental Crops 0.25 lb ai/A 53 260 530 3,400

Nursery Ornamentals 0.25 lb ai/A 35 180 350 2,300

Sod 0.95 lb ai/A 6.9 35 69 460

Orchards/Vineyards 0.25 lb ai/A 53 260 530 3,400

Field Crop, Typical 0.33 lb ai/A 20 100 200 1,300

Field Crop, High Acreage 0.4 lb ai/A 6.6 33 66 430

Mixing/Loading Granulars for Aerial Application Sod 0.95 lb ai/A 15 73 150 300

Mixing/Loading Granulars for Tractor-Drawn 

Spreader Applications

Golf Course (Fairways, Tees, Greens) 0.95 lb ai/A 130 640 1,300 2,600

Golf Course (Tees and Greens) 0.95 lb ai/A 1,000 5,100 10,000 21,000

Sod 0.95 lb ai/A 64 230 640 1,300

Mixing/Loading Liquids for Aerial Application

Nursery Ornamentals 0.25 lb ai/A 1,400 7,200 14,000 6,600

Orchards/Vineyards 0.25 lb ai/A 250 1,200 2,500 1,100

Sod 0.99 lb ai/A 62 310 620 290
Page 55 of 75

Table D.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for the Registered Conventional Uses of Azoxystrobin1.

Exposure Scenario Crop or Target1 Maximum

Application Rate2

Inhalation MOE

(LOC = 300)

Baseline PF5 Respirator PF10 Respirator Engineering Control

Field Crop, Typical 0.33 lb ai/A 190 930 1,900 860

Field Crop, High Acreage 0.4 lb ai/A 45 220 450 210

Mixing/Loading Liquids for Airblast Application

Nursery Ornamentals 0.25 lb ai/A 4,300 22,000 43,000 20,000

Orchards/Vineyards 0.25 lb ai/A 2,200 11,000 22,000 9,900

Mixing/Loading Liquids for Chemigation 

Application

Orchards/Vineyards 0.25 lb ai/A 250 1,200 2,500 1,100

Sod 0.99 lb ai/A 62 310 620 290

Field Crop, Typical 0.33 lb ai/A 190 930 1,900 860

Field Crop, High Acreage 0.4 lb ai/A 150 770 1,500 710

Greenhouse Ornamentals 0.26 lb ai/A 1,400 6,900 14,000 6,400

Nursery Ornamentals 0.25 lb ai/A 1,400 7,200 14,000 6,600

Mixing/Loading Liquids for Groundboom 

Application

Golf Course (Tees and Greens) 0.99 lb ai/A 4,400 22,000 44,000 20,000

Golf Course (Fairways, Tees, Greens) 0.99 lb ai/A 550 2,700 5,500 2,500

Field-Grown Ornamentals 0.25 lb ai/A 2,200 11,000 22,000 9,900

Nursery Ornamentals 0.25 lb ai/A 1,400 7,200 14,000 6,600

Greenhouse Ornamentals 0.26 lb ai/A 1,400 6,900 14,000 6,400

Sod 0.99 lb ai/A 270 1,400 2,700 1,300

Orchards/Vineyards 0.25 lb ai/A 2,200 11,000 22,000 9,900

Field Crop, Typical 0.33 lb ai/A 820 4,100 8,200 3,800

Field Crop, High Acreage 0.4 lb ai/A 270 1,300 2,700 1,200

Applicator

Applying Sprays with Aerial Application Equipment

Nursery Ornamentals 0.25 lb ai/A

N/A

32,000

Orchards/Vineyards 0.25 lb ai/A 5,400

Sod 0.99 lb ai/A 1,400

Field Crop, Typical 0.33 lb ai/A 4,100

Field Crop, High Acreage 0.4 lb ai/A 990

Applying Sprays with Airblast Application 

Equipment

Nursery Ornamentals 0.25 lb ai/A 98 490 980 6,800

Orchards/Vineyards 0.25 lb ai/A 49 250 490 3,400

Applying Sprays with Groundboom Application 

Equipment

Golf Course (Tees and Greens) 0.99 lb ai/A 1,400 6,900 14,000 39,000

Golf Course (Fairways, Tees, Greens) 0.99 lb ai/A 170 860 1,700 4,800

Field-Grown Ornamentals 0.25 lb ai/A 680 3,400 6,800 19,000

Nursery Ornamentals 0.25 lb ai/A 450 2,300 4,500 13,000
Page 56 of 75

Table D.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for the Registered Conventional Uses of Azoxystrobin1.

Exposure Scenario Crop or Target1 Maximum

Application Rate2

Inhalation MOE

(LOC = 300)

Baseline PF5 Respirator PF10 Respirator Engineering Control

Greenhouse Ornamentals 0.26 lb ai/A 440 2,200 4,400 12,000

Sod 0.99 lb ai/A 86 430 860 2,400

Orchards/Vineyards 0.25 lb ai/A 680 3,400 6,800 19,000

Field Crop, Typical 0.33 lb ai/A 260 1,300 2,600 7,200

Field Crop, High Acreage 0.4 lb ai/A 85 430 850 2,400

Applying Granulars with Aerial Application 

Equipment Sod 0.95 lb ai/A N/A 19

Applying Granulars with a Tractor-Drawn Spreader

Golf Course (Fairways, Tees, Greens) 0.95 lb ai/A 180 900 1,800 980

Golf Course (Tees and Greens) 0.95 lb ai/A 1,400 7,200 14,000 7,900

Sod 0.95 lb ai/A 90 450 900 490

Flagger

Flagging for Aerial Applications (Sprays) Sod 0.95 lb ai/A 71 350 710

N/A

Flagging for Aerial Applications (Granulars) Sod 0.95 lb ai/A 170 820 1,700

Mixer/Loader/Applicator

Mixing/Loading/Applying Dry Flowable or Liquid 

Formulations with Backpack Sprayer

Orchard/Vineyard, Christmas Tree 

Farm, Nursery Ornamentals (Ground 

Directed)

0.025 lb ai/gal

1,800 9,100 18,000 N/A

Orchard/Vineyard, Christmas Tree 

Farm, Nursery Ornamentals (Broadcast)

0.025 lb ai/gal 120 600 1,200

Landscaping (Plants, Flowers, Trees, N/A

Turf) (Broadcast Treatment)

0.119 lb ai/gal 25 130 250

Landscaping Turf (Spot Treatment) 0.119 lb ai/gal 380 1,900 3,800

Mixing/Loading/Applying Dry Flowable or Liquid 

Formulations with a Manually Pressurized 

Handwand

Christmas Tree Farm, Nursery 

Ornamentals (Broadcast) 0.025 lb ai/gal 270 1,400 2,700

N/A

Landscaping (Plants, Flowers, Trees, 

Turf)

0.119 lb ai/gal 58 290 580

Mixing/Loading/Applying Dry Flowable 

Formulations with a Mechanically Pressurized 

Handwand

Orchard/Vineyard, Christmas Tree 

Farm, Nursery Ornamentals 0.025 lb ai/gal 38 190 380

Golf Course (Tees, Greens, Fairways) 0.95 lb ai/A 24 120 240 N/A

Landscaping (Trees, Shrubs, Bushes) 0.119 lb ai/gal 8 40 79

Field Crop, Typical 0.033 lb ai/gal 29 140 290

Mixing/Loading/Applying Liquids with a Manually 

Pressurized Handwand Greenhouse Ornamentals 0.026 lb ai/gal 260 1,300 2,600 N/A

Mixing/Loading/Applying Liquids with a Orchard/Vineyard, Christmas Tree 0.025 lb ai/gal 38 190 380 N/A
Page 57 of 75

Table D.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for the Registered Conventional Uses of Azoxystrobin1.

Exposure Scenario Crop or Target1 Maximum

Application Rate2

Inhalation MOE

(LOC = 300)

Baseline PF5 Respirator PF10 Respirator Engineering Control

Mechanically Pressurized Handwand Farm, Nursery Ornamentals

Greenhouse Ornamentals 0.017 lb ai/gal 4 20 40

Golf Course (Tees, Greens, Fairways), 

Landscaping Turf, 0.01 lb ai/A 50,000 250,000 500,000

Landscaping (Trees, Shrubs Bushes) 0.01 lb ai/gal 8 40 79

Field Crop, Typical 0.033 lb ai/gal 29 140 290

Loading/Applying Granular Formulations with a 

Rotary Spreader Golf Course (Fairways, Tees, Greens) 0.95 lb ai/A 99 500 990 N/A

1 Assessment is based on maximum registered azoxystrobin application rate for each scenario. Crops were grouped according to registered application rates and applicable exposure scenarios 

to cover all registered use sites. Shaded MOEs represent risk estimates of concern (LOC = 300). 

2 Inhalation MOE = Inhalation HED (mg/kg/day) ÷ Inhalation Dose. Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre 

or gal) × Area Treated or Amount Handled Daily (A or gal/day) ÷ BW (kg). Unit Exposures are outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference 

Table17”, which, along with additional information on HED policy on use of surrogate data, including descriptions of the various sources, can be found at the Agency website18. Area or 

Amount Treated Information is available in ExpoSAC Policy 9.1. 

Table 8.1.2. Occupational Handler Non-Cancer Exposure and Risk Estimates for the Registered Post-Harvest Uses of Azoxystrobin.

Exposure Scenario Crop or Target

Maximum

Application Rate1

Inhalation MOE (LOC = 300)

lb ai/gal solution Baseline5 PF5 PF10

Mixing/Loading For Post-Harvest Treatment 

in a Closed Automated System

Citrus 0.15 15 N/A N/A

Potatoes 0.0000049 460,000 N/A N/A

Bananas 0.00034 6,600 N/A N/A

Mixing/Loading Dry Flowable Formulations 

in an Automated System Bananas 0.00034 62 310 620

Mixing/Loading Liquids in an Automated 

System

Citrus 0.15 5.7 29 57

Bananas2 0.00034 2500 13,000 25,000

Applying Direct Post-Harvest Sprays with a 

Mechanically Pressurized Handgun

Citrus 0.15 0.32 1.6 3.2

Bananas2 0.00034 140 700 1,400

1 Based on registered labels (Reg. No. 89442-21, 100-1098, 100-1093).

2 Based on ExpoSAC Post-Harvest Policy. 

3 halation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/ gal) × Area Treated or Amount Handled Daily (gal/day) ÷ BW (80 kg).

 

17 Available: http://www.epa.gov/opp00001/science/handler-exposure-table.pdf

18 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
Page 58 of 75

4 Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). Shaded MOEs indicated MOEs of concern (LOC = 300).

5 For closed automated system, baseline exposures represent engineering control protection. “Baseline” for all other scenarios represents no respirator. 

Table D.3. Primary Seed Treatment Exposure and Risk Estimates for the Registered Uses of Azoxystrobin – Liquids.

Scenario Application Rate 

(lb ai/lb seed)1

Amount of 

Seed Treated 

(lb/day)3 SOP 

15.1

Inhalation Dose 

(mg/kg/day)

Inhalation MOE 

(LOC = 300)

Baseline PF5 PF10 EC Baseline PF5 PF 10 EC 

Loader/Applicator

Corn (field, pop, sweet), 

Peanuts, Bulb Vegetables, 

Cotton, Cucurbits, Okra, 

Ornamental Bulbs

0.000244 339,500 0.000352 0.000070 0.000035 0.000045 170 840 1700 1300

Rice 0.000070 302,500 0.000104 0.000018 0.000009 0.000011 570 3300 6600 5200

Barley, Triticale, Wheat, 

Sorghum, 0.000244 360,000 0.000433 0.000075 0.000037 0.000047 140 790 1600 1200

Brassica, Eggplant, Leafy 

Vegetables, Bell Pepper, 

Non-Bell Pepper, Tomato, 

Watercress, Ornamental 

Seed, Turf

0.000244 3,000 0.0000036 0.00000062 0.00000031 0.00000039 16,000 95000 190000 150000

Leaves of Root and Tuber 

Vegetables, Root 

Vegetables, Tuberous and 

Corm Vegetables

0.000244 800,000 0.000962 0.000166 0.000083 0.000105 61 360 710 560

Potato 0.000244 800,000 0.018106 0.003123 0.001562 0.000105 3 19 38 560

Legume Vegetables 0.000244 281,250 0.000338 0.000058 0.000029 0.000037 170 1000 2000 1600

Soybean 0.00003 281,250 0.000042 0.0000072 0.0000041 0.000005 1,400 8200 16000 13000

Sunflower 0.00244 339,500 0.004082 0.000704 0.000352 0.000445 14 84 170 130

Cotton 0.00018 339,500 0.000301 0.000052 0.000026 0.000033 200 1100 2300 1800

Sewer

Corn (field, pop, sweet), 

Peanuts, Bulb Vegetables, 

Cotton, Cucurbits, Okra, 

Ornamental Bulbs

0.000244 339,500 0.000276 0.000048 0.000024 N/A 210 1200 2500 N/A

Rice 0.00007 302,500 0.000071 0.000012 0.0000061 N/A 840 4800 9700 N/A
Page 59 of 75

Table D.3. Primary Seed Treatment Exposure and Risk Estimates for the Registered Uses of Azoxystrobin – Liquids.

Scenario Application Rate 

(lb ai/lb seed)1

Amount of 

Seed Treated 

(lb/day)3 SOP 

15.1

Inhalation Dose 

(mg/kg/day)

Inhalation MOE 

(LOC = 300)

Baseline PF5 PF10 EC Baseline PF5 PF 10 EC 

Barley, Triticale, Wheat, 

Sorghum, 0.000244 360,000 0.000293 0.000051 0.000025 N/A 200 1200 2300 N/A

Brassica, Eggplant, Leafy 

Vegetables, Bell Pepper, 

Non-Bell Pepper, Tomato, 

Watercress, Ornamental 

Seed, Turf,

0.000244 3,000 0.0000024 0.00000042 0.00000021 N/A 24,000 140000 280000 N/A

Leaves of Root and Tuber 

Vegetables, Potato, Root 

Vegetables, Tuberous and 

Corm Vegetables

0.000244 800,000 0.000651 0.000112 0.000056 N/A 91 530 1100 N/A

Legume Vegetables 0.000244 281,250 0.000229 0.000039 0.000020 N/A 260 1500 3000 N/A

Soybean 0.00003 281,250 0.000028 0.0000049 0.000002 N/A 2,100 12000 24000 N/A

Sunflower 0.00244 339,500 0.002761 0.00048 0.000238 N/A 21 120 250 N/A

Cotton 0.00018 339,500 0.000204 0.000035 0.000018 N/A 290 1700 3400 N/A

Bagger

Corn (field, pop, sweet), 

Peanuts, Bulb Vegetables, 

Cotton, Cucurbits, Okra, 

Ornamental Bulbs

0.000244 339,500 0.00019 0.000033 0.000017 N/A 310 1800 3600 N/A

Rice 0.00007 302,500 0.000049 0.0000085 0.0000042 N/A 1,200 7000 14000 N/A

Barley, Triticale, Wheat, 

Sorghum, 0.000244 360,000 0.000204 0.000035 0.000018 N/A 290 1700 3400 N/A

Brassica, Eggplant, Leafy 

Vegetables, Bell Pepper, 

Non-Bell Pepper, Tomato, 

Watercress, Ornamental 

Seed, Turf,

0.000244 3,000 0.0000017 0.00000029 0.00000015 N/A 35,000 200000 400000 N/A

Leaves of Root and Tuber 

Vegetables, Potato, Root 

Vegetables, Tuberous and 

Corm Vegetables

0.000244 800,000 0.00045 0.000078 0.000039 N/A 130 760 1500 N/A

Legume Vegetables 0.000244 281,250 0.00016 0.000027 0.000014 N/A 370 2100 4300 N/A

Soybean 0.00003 281,250 0.000020 0.0000034 0.0000017 N/A 3,000 17000 35000 N/A

Sunflower 0.00244 339,500 0.0019 0.000331 0.000166 N/A 31 180 360 N/A

Cotton 0.00018 339,500 0.000142 0.000024 0.000012 N/A 420 2400 4800 N/A
Page 60 of 75

Table D.3. Primary Seed Treatment Exposure and Risk Estimates for the Registered Uses of Azoxystrobin – Liquids.

Scenario Application Rate 

(lb ai/lb seed)1

Amount of 

Seed Treated 

(lb/day)3 SOP 

15.1

Inhalation Dose 

(mg/kg/day)

Inhalation MOE 

(LOC = 300)

Baseline PF5 PF10 EC Baseline PF5 PF 10 EC 

Multiple Activities

Corn (field, pop, sweet), 

Peanuts, Bulb Vegetables, 

Cotton, Cucurbits, Okra, 

Ornamental Bulbs

0.000244 339,500 0.00192 0.000331 0.00017 0.000045 31 180 360 1300

Rice 0.00007 302,500 0.00049 0.000085 0.000042 0.000011 120 700 1400 5200

Barley, Triticale, Wheat, 

Sorghum, 0.000244 360,000 0.00204 0.000351 0.00018 0.000047 29 170 340 1200

Brassica, Eggplant, Leafy 

Vegetables, Bell Pepper, 

Non-Bell Pepper, Tomato, 

Watercress, Ornamental 

Seed, Turf,

0.000244 3,000 0.000017 0.0000029 0.0000015 0.00000039 3,500 20000 40000 150000

Leaves of Root and Tuber 

Vegetables, Potato, Root 

Vegetables, Tuberous and 

Corm Vegetables

0.000244 800,000 0.0045 0.00078 0.00039 0.000105 13 76 150 560

Legume Vegetables 0.000244 281,250 0.0016 0.00027 0.00014 0.000037 37 210 430 1600

Soybean 0.00003 281,250 0.00020 0.000034 0.000017 0.0000045 300 1700 3500 13000

Sunflower 0.00244 339,500 0.019 0.0033 0.0017 0.00045 3 18 36 130

Cotton 0.00018 339,500 0.0014 0.00024 0.00012 0.000033 42 240 480 1800

1 Seed Treatment Application rates based on the registered liquid azoxystrobin labels (100-1159, 100-1177, 100-1208, 100-1286, 100-1352, 100-1369, 100-1384, 100-1399, 100-1405, 100-

1449, 100-1450). 

2 Unit Exposures from HED Exposure Science Advisory Council Policy 14: Standard Operating Procedures for Seed Treatment (baseline inhalation = no respirator). Unit Exposures for PF5 

and PF10 respirators were adjusted in the inhalation dose calculation accordingly (baseline inhalation UE ÷ 5 = PF5 UE, etc). 

3 HED default for lb seed treated/planted per day from HED Exposure Science Advisory Council Interim Policy 15.1 and the BEAD memo “Acres Planted Per Day and Seeding Rates of Crops 

Grown in the United States” (J. Becker, March 2011).

4 Daily Inhalation Dose (mg/kg/day) = daily inhalation unit exposure (mg/lb ai) × application rate (lb ai/lb seed) × amount planted (lb seed/day) ÷ body weight (80 kg adult).

5 Inhalation MOE = Inhalation POD (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). Short-term level of concern = 300. Shaded MOEs indicated MOEs of concern (LOC = 300).

Table D.4. Secondary Seed Treatment Exposure and Risk Estimates for the Registered Uses of Azoxystrobin – Liquids.

Scenario

Application 

Rate (lb 

ai/lb seed)1

Inhalation 

UE

Baseline

(mg/lb ai)

Amount 

of Seed 

Planted 

(lb /A)

Acres 

Planted 

(A/day) 

SOP 15

Inhalation Dose (mg/kg/day) Inhalation MOE 

(LOC = 300)

Baseline PF5 PF10 Baseline PF5 PF 10

Planters
Page 61 of 75

Table D.4. Secondary Seed Treatment Exposure and Risk Estimates for the Registered Uses of Azoxystrobin – Liquids.

Scenario

Application 

Rate (lb 

ai/lb seed)1

Inhalation 

UE

Baseline

(mg/lb ai)

Amount 

of Seed 

Planted 

(lb /A)

Acres 

Planted 

(A/day) 

SOP 15

Inhalation Dose (mg/kg/day) Inhalation MOE 

(LOC = 300)

Baseline PF5 PF10 Baseline PF5 PF 10

Barley 0.000244

0.0034

138 200 0.00033 0.000057 0.000029 180 

1,000 

 

2,100 

Bell pepper 0.000244 1.39 80 0.0000013 0.00000023 0.00000012 44,000 

260,000 

 

510,000 

Brassica 0.000244 2.64 80 0.0000025 0.00000044 0.00000022 23,000 

130,000 

 

270,000 

Bulb 

vegetables 0.000244

0.0034

31 80 0.0000302 0.0000052 0.0000026 2,000

 

11,000 

 

23,000 

Corn 

(field) 0.000244 30 200 0.000071 0.0000123 0.0000061 830

 

4,800 

 

9,600 

Corn (pop) 0.000244 22 200 0.000053 0.0000091 0.0000046 1,100 

6,500 

 

13,000 

Corn 

(Sweet) 0.000244 33 200 0.000080 0.0000138 0.0000069 740 

4,300 

 

8,600 

Cotton 0.000244 19 200 0.000045 0.0000078 0.0000039 1,300 

7,500 

 

15,000 

Cucurbits 0.000244 12 80 0.000011 0.0000019 0.00000096 5,300 

31,000 

 

61,000 

Eggplant 0.000244 7.56 80 0.0000073 0.0000013 0.0000006 8,100 

47,000 

 

94,000 

Leafy 

Vegetables 0.000244 0.78 80 0.00000075 0.0000001 0.0000001 78,000 

450,000 

 

910,000 

Leaves of 

root and 

tuber 

vegetables

0.000244 14 80 0.000013 0.0000023 0.0000012 4,400

 

26,000 

 

51,000 

Legume 

Vegetables 0.000244 327 80 0.00031 0.0000542 0.000027 190 1,100 

 

2,200 

Okra 0.000244 23 80 0.000022 0.0000038 0.0000019 2,700 

16,000 

 

31,000 

Ornamental 

bulbs 0.000244 4.48 80 0.0000043 0.00000074 0.00000037 14,000 79,000 

 

160,000 
Page 62 of 75

Table D.4. Secondary Seed Treatment Exposure and Risk Estimates for the Registered Uses of Azoxystrobin – Liquids.

Scenario

Application 

Rate (lb 

ai/lb seed)1

Inhalation 

UE

Baseline

(mg/lb ai)

Amount 

of Seed 

Planted 

(lb /A)

Acres 

Planted 

(A/day) 

SOP 15

Inhalation Dose (mg/kg/day) Inhalation MOE 

(LOC = 300)

Baseline PF5 PF10 Baseline PF5 PF 10

Ornamental 

seed 0.000244 4.48 80 0.0000043 0.00000074 0.00000037 14,000 79,000 

 

160,000 

Peanut 0.000244 228 80 0.00022 0.0000379 0.0000189 270 

1,600 

 

3,100 

Pepper-non 

bell 0.000244 4.18 80 0.00000402 0.0000007 0.00000035 15,000 85,000 

 

170,000 

Potato 0.000244 6,970 300 0.025 0.0043 0.0022 2.3 14 27 

Rice 0.00007 156 200 0.00011 0.000019 0.0000093 550 3,200 6,300 

Root 

Vegetables 0.000244 0.12 80 0.00000011 0.000000020 0.0000000098 520,000 3,000,000 6,000,000 

Sorghum 0.0002

0.0034

59 80 0.000046 0.0000080 0.0000040 1,300 7,400 15,000 

Soybean 0.00003 167 200 0.000049 0.0000085 0.0000043 1,200 6,900 14,000 

Sunflower 0.00244 4.00 80 0.000039 0.0000066 0.0000033 1,500 8,900 18,000 

Tomato 0.000244 1.09 80 0.0000011 0.00000018 0.0000000903 56,000 330,000 650,000 

Triticale 0.000244 116 200 0.00028 0.0000482 0.0000241 210 1,200 2,400 

Tuberous 

and Corm 

Vegetables

0.000244 6,970 300 0.025 0.00434 0.0022 2.3 14 27 

Turf 0.000244 5,238 80 0.00504 0.00087 0.00043 12 68 140 

Watercress 0.000244 17 80 0.000017 0.0000028 0.0000014 3,600 21,000 42,000 

Wheat 0.000244 188 200 0.00045 0.000078 0.000039 130 760 1,500 

1 Seed Treatment Application rates based on the registered liquid azoxystrobin labels (100-1159, 100-1177, 100-1208, 100-1286, 100-1352, 100-1369, 100-1384, 100-1399, 100-1405, 100-

1449, 100-1450). 

2 Unit Exposures from HED Exposure Science Advisory Council Policy 14: Standard Operating Procedures for Seed Treatment (baseline inhalation = no respirator). Unit Exposures for PF5 

and PF10 respirators were adjusted in the inhalation dose calculation accordingly (baseline inhalation UE ÷ 5 = PF5 UE, etc). 

3 HED default for lb seed treated/planted per day from HED Exposure Science Advisory Council Interim Policy 15.1 and the BEAD memo “Acres Planted Per Day and Seeding Rates of Crops 

Grown in the United States” (J. Becker, March 2011).

4 Daily Inhalation Dose (mg/kg/day) = daily inhalation unit exposure (mg/lb ai) × application rate (lb ai/lb seed) × amount planted (lb seed/day) ÷ body weight (80 kg adult).

5 Inhalation MOE = Inhalation POD (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). Short-term level of concern = 300. Shaded MOEs indicated MOEs of concern (LOC = 300).
Page 63 of 75

1 Seed Treatment Application rates based on the registered dust azoxystrobin labels (100-1190, 100-1438). 

2 Unit Exposures from HED Exposure Science Advisory Council Policy 14: Standard Operating Procedures for Seed Treatment (baseline inhalation = no respirator). Unit Exposures for PF5 

and PF10 respirators were adjusted in the inhalation dose calculation accordingly (baseline inhalation UE ÷ 5 = PF5 UE, etc). The wettable powder mixing/loading UE (PHED Scenario 

4/PHED Scenario 5) was used a surrogate for loader/applicator, sewer, bagger, and multiple activity scenarios for baseline and engineering control dust exposures. 

3 HED default for lb seed treated/planted per day from HED Exposure Science Advisory Council Interim Policy 15.1 and the BEAD memo “Acres Planted Per Day and Seeding Rates of Crops 

Grown in the United States” (J. Becker, March 2011).

4 Daily Inhalation Dose (mg/kg/day) = daily inhalation unit exposure (mg/lb ai) × application rate (lb ai/lb seed) × amount planted (lb seed/day) ÷ body weight (80 kg adult).

5 Inhalation MOE = Inhalation POD (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). Short-term level of concern = 300. Shaded MOEs indicated MOEs of concern (LOC = 300). 

1 Seed Treatment Application rates based on the registered dust azoxystrobin labels (100-1190, 100-1438). 

2 Unit Exposures from HED Exposure Science Advisory Council Policy 14: Standard Operating Procedures for Seed Treatment (baseline inhalation = no respirator). Unit Exposures for PF5 

and PF10 respirators were adjusted in the inhalation dose calculation accordingly (baseline inhalation UE ÷ 5 = PF5 UE, etc). The wettable powder mixing/loading UE (PHED Scenario 

4/PHED Scenario 5) was used a surrogate for loader/applicator, sewer, bagger, and multiple activity scenarios for dust exposures. 

3 HED default for lb seed treated/planted per day from HED Exposure Science Advisory Council Interim Policy 15.1 and the BEAD memo “Acres Planted Per Day and Seeding Rates of Crops 

Table D.5. Seed Treatment Exposure and Risk Estimates for the Registered Uses of Azoxystrobin –Dust Formulations.

Scenario

Application 

Rate (lb 

ai/lb seed)1

Inhalation 

UE Baseline

(mg/lb ai)2

Inhalation 

UE 

Engineering 

Control 

(mg/lb ai)2

Amount of 

Seed Treated 

or Planted 

(lb/day)3

Inhalation Dose (mg/kg/day) Inhalation MOE

(LOC = 300)

Baseline4 PF54 PF104 EC4 Baseline5 PF55 PF105 Engineering 

Control5

Loader/Applicator, Sewer, Bagger, Multiple Activities

Peanuts 0.00008 0.043 0.00024 339,500 0.015 0.0029 0.0015 0.0015 4 20 40 40

Planters

Peanuts 0.00008 1.69 N/A 228 0.00062 0.00012 0.000062 N/A 95 480 950 N/A

Table D.6. Seed Treatment Exposure and Risk Estimates for the Registered Uses of Azoxystrobin –Dry Flowable Formulations.

Scenario

Application 

Rate (lb ai/lb 

seed)1

Inhalation UE 

Baseline 

(mg/lb ai)2

Inhalation UE 

Engineering 

Control (mg/lb 

ai)2

Amount of 

Seed Treated 

or Planted 

(lb/day)3

Inhalation Dose (mg/kg/day) Inhalation MOE

(LOC = 300)

Baseline4 PF104 Engineering 

Control4 Baseline5 PF105 Engineering Control5

Loader/Applicator, Sewer, Bagger, Multiple Activities

Cotton 0.0002 0.00896 0.0024 339,500 0.0089 0.00088 0.00024 6.7 67 250

Planters

Cotton 0.0002 0.00896 N/A

19

(lb planted/day)

200 (Acres 

Planted per day 

(SOP 15))

0.000098 N/A N/A 600 N/A N/A
Page 64 of 75

Grown in the United States” (J. Becker, March 2011).

4 Daily Inhalation Dose (mg/kg/day) = daily inhalation unit exposure (mg/lb ai) × application rate (lb ai/lb seed) × amount planted (lb seed/day) ÷ body weight (80 kg adult).

5 Inhalation MOE = Inhalation POD (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). Short-term level of concern = 300. Shaded MOEs indicated MOEs of concern (LOC = 300).

Table D.7. Azoxystrobin Occupational Handler Inhalation MOEs for Preserved Paint 

Scenario Application 

Rate1

Amount Paint 

Manufactured or 

Applied (lb/day)2

Amount Ai 

Handled 

(lb/day)

Unit Exposure

(mg/lb ai) 3,4,5

Daily Dose6

(mg/kg/day)

Inhalation 

MOE7

(LOC =300)

Adding Azoxystrobin to Paint During Paint Manufacture

Open pour liquid 

(No Respirator)

0.31% ai by wt 20,000 lb

(2,000 ga x 10 lb/ga) 62

0.0017 0.0013 30

Open pour liquid

(PF10 Respirator) 0.017 0.00013 300

Application of Paint Containing Azoxystrobin

Airless sprayer

0.31% ai by wt

500

(50 ga x 10 lb/ga) 1.6 0.560 0.010 6

Brush/Roller 50

(5 ga x 10 lb/ga) 0.16 0.20 0.0004 150

1 Based upon maximum rate listed on label #39967-86.

2 AD Standard Operating Procedures (SOPs) for Occupational Exposure Assessment (March 31, 2011).

3 Unit Exposure value is from AEATF Liquid Pour Study. 

4 Unit Exposure value divided by 10 to account for the use of a PF10 Elastomeric Half Face Respirator.

5 HED Occupational Pesticide Handler Unit Exposure Surrogate Reference Table (March, 2013).

6 Daily Dose = [Amount ai Handled (lb) * Unit Exposure (mg/lb)] ÷ Body Weight (80 kg).

7 MOE = HED (0.059 mg/kg/day for 8 hour 5 day per week exposure at 16.7 liters/minute) ÷ Daily Dose (mg/kg/day).
Page 65 of 75

1. Used the highest ppm rate found on the registered labels (EPA Reg. No. 100-1093, 89442-21, 100-1098)

2. Based on Table 2 in ExpoSAC Policy/Guidance “Assessment of Occupational Exposure for Post-Harvest Commodity Pesticide Treatments” (M. Crowley, 23-MAR-2012); Level of mitigation: Tshirt/NG = t-shirt and no gloves; NR = no respirator.

3. Inhalation Dose = [Unit Exposure (μg/% ai) * Application Rate (% ai in solution) * Adjustment Factor (0.001 μg/mg)] ÷ Body Weight (80 kg).

4. Inhalation MOE = Inhalation POD (0.059 mg/kg/day) ÷ Inhalation Dose.

Table D.9. Occupational Post-application Non-Cancer Indirect Inhalation Exposure and Risk Estimates for Azoxystrobin.

Crop/Site

Max App. Rate

(% ai in 

solution)

Inhalation Unit Exposure (μg/% 

ai)1

Inhalation Dose

(mg/kg/day)2 MOE3

Baseline PF5 PF10 Baseline PF5 PF10 Baseline PF5 PF10

Citrus –

Concentrated 

Solution

0.49

307 61.4 30.7

0.0019 0.00037 0.00019 32 160 320

Citrus –

Diluted 

Solution 

0.12 0.00046 0.000093 0.000046 130 640 1,300

Bananas 0.04 0.000039 0.0000077 0.0000039 1,500 7,600 15,000

Potato 0.000013 0.000000050 0.000000010 0.0000000050 1,200,000 5,900,000 12,000,000

1. Based on Table 4 in ExpoSAC Policy/Guidance “Assessment of Occupational Exposure for Post-Harvest Commodity Pesticide Treatments” (M. Crowley, 23-MAR-2012); Level of mitigation: NR = 

no respirator.

Table D.8. Occupational Post-application Non-Cancer Exposure and Risk Estimates for Azoxystrobin

Crop/Site Activities

Max App. 

Rate

(% ai in 

solution)1

Inhalation Unit Exposure 

(μg/% ai)2

Inhalation Dose (mg/kg/day)3Inhalation MOE4(LOC = 300)

Baseline PF5 PF10 Baseline PF5 PF10 Baseline PF5 PF10

Citrus –

Concentrated 

Solution

Sorter

0.48

6720 1340 672 0.041 0.0081 0.0041 1.5 7.3 15

Packer 6760 1350 675 0.041 0.0081 0.0041 1.5 7.3 15

Citrus –

Diluted 

Solution

Sorter

0.12

6720 1340 672 0.0101 0.0020 0.0010 5.8 29 58

Packer 6760 1350 675 0.0101 0.0020 0.0010 5.8 29 58

Bananas

Sorter

0.01

6720 1340 672 0.0008 0.0002 0.0001 70 350 700

Packer 6760 1350 675 0.0008 0.0002 0.0001 70 350 700

Potato

Sorter 0.000013 6720 1340 672 0.000000011 0.0000000022 0.0000000011 5,200,000 26,000,000 52,000,000

Packer 0.000013 6760 1350 675 0.000000011 0.0000000022 0.0000000011 5,200,000 26,000,000 52,000,000
Page 66 of 75

2. Inhalation Dose = [Unit Exposure (μg/% ai) * Application Rate (% ai in solution) * Adjustment Factor (0.001 μg/mg)] ÷ Body Weight (80 kg)].

3. Inhalation MOE = Inhalation POD (0.059 mg/kg/day)/Inhalation Dose.
Page 67 of 75

Appendix E. Azoxystrobin IRL Sheet

Azoxystrobin (122810)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

§180.507 (a) General. (1) Compliance 

with the tolerance levels specified in 

the table is to be determined by 

measuring only the 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] 

methyl (αE)-2-[[6-(2-

cyanophenoxy)-4-

pyrimidinyl]oxy]-α-

(methoxymethylene)benzenea

cetate, including the isomer 

(Z)-methyl 2-[[6-(2-

cyanophenoxy)-4-

pyrimidinyl]oxy]-α-

(methoxymethylene)benzenea

cetate

Azoxystrobin

The residue is fat 

soluble. 

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

US Canada Mexico2 Codex3

Acerola 2.0 2

Almond, hulls 4.0 7

Animal feed, nongrass, group 

18, forage

45

Animal feed, nongrass, group 

18, hay

120

Artichoke, globe 4.0 5

Asparagus 0.04 0.04 0.01(*)

Atemoya 2.0 2

Avocado 2.0 2

Banana * 2 2 banana, plantain

Barley, bran 6.0 1.5

Barley, forage 25

Barley, grain 3.0 0.03

Barley, hay 10.0

Barley, straw 15.0

Berry, low growing, 

subgroup 13-07G, except 

cranberry

10.0 5.0 (Berries & other 

small fruits, except 

cranberry, grapes 

and strawberry)

10 strawberry

Biriba 2.0 2

Brassica, head and stem, 

subgroup 5A

3.0 3 (except cavalo broccoli) 5 Brassica (cole or 

cabbage) 

vegetables, head 

cabbage, 

flowerhead 

Brassicas

Brassica, leafy greens, 

subgroup 5B

25 25 (except mizuna)
Page 68 of 75

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

Bushberry subgroup 13-07B 5.0 3 

4 gooseberries

5.0 (Berries & other 

small fruits, except 

cranberry, grapes 

Caneberry subgroup 13-07A 5.0 5 and strawberry)

Canistel 2.0 2

Cherimoya 2.0 2

Cilantro, leaves 30.0

Citrus, dried pulp 20.0

Citrus, oil 40.0 40 0.1

Coffee, green bean1 0.03 0.03 coffee beans

Corn, field, forage 12.0

Corn, field, grain 0.05 0.03 0.02

Corn, field, refined oil 0.3 0.2 0.1

Corn, field, stover 25.0 40 (dry wt)

Corn, pop, grain 0.05 0.03

Corn, pop, stover 25.0

Corn, sweet, forage 12.0

Corn, sweet, kernel plus cob 

with husks removed

0.05 0.03

Corn, sweet, stover 25.0

Cotton, gin byproducts 45

Cottonseed subgroup 20C 0.7 0.7 undelinted cotton seeds 0.7 cottonseed

Cranberry 0.50 0.5 0.5

Custard apple 2.0 2

Dragon fruit 2.0 2

Feijoa 2.0 2

Fruit, citrus, group 10-10 15.0 15 15

Fruit, small vine climbing, 

except fuzzy kiwifruit, 

subgroup 13-07F

2.0 4 2 grapes

Fruit, stone, group 12 1.5 2 2

Ginseng1 0.5 0.5 ginseng roots 0.1ginseng

0.3 ginseng, dried 

including red 

ginseng

0.5 ginseng extracts

Grain, aspirated fractions 420

Grass, forage 15

Grass, hay 20

Guava 2.0 2

Herb Subgroup 19A, dried 

leaves

260 260 300 dried herbs 

(except hops (dry))

Herb Subgroup 19A, fresh 

leaves

50 50 70 herbs

Hop, dried cones 20.0 20 30

Ilama 2.0 2

Jaboticaba 2.0 2

Jackfruit 2.0 2

Longan 2.0 2
Page 69 of 75

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

Loquat 2.0 2

Lychee 2.0 2

Mango 2.0 2 0.7

Nut, tree, group 14 0.02 0.02 0.01

Oats, forage 5.0

Oats, grain 1.5 0.03 1.5

Oats, hay 10.0

Oats, straw 3.0

Onion, bulb, subgroup 3-07A 1.0 1 10

Onion, green, subgroup 3-

07B

7.5 7.5 

Papaya 2.0 2 0.3

Passionfruit 2.0 2

Pawpaw 2.0 2

Pea and bean, dried shelled, 

except soybean, subgroup 6C

0.5 0.2 0.07 pluses (except 

soya beans)

Pea and bean, succulent 

shelled, subgroup 6B

0.5 0.02 succulent shelled

(blackeyed peas, broad beans, 

cowpeas, lima beans, southern 

peas

0.2 English peas, garden peas, 

green peas, peas, pigeon peas

3 legume vegetables

Peanut 0.2 0.2 0.2

Peanut, hay 15.0 30 peanut fodder

Peanut, refined oil 0.6 0.6

Pear, Asian1 0.07

Pepper/eggplant subgroup 8-

10B

3.0 3 3 fruiting vegetables 

other than cucurbits 

(except mushrooms 

and sweet corn)

30 Chilli pepper 

(dry)

Peppermint, tops 30 30

Persimmon 2.0 2

Pistachio 0.50 0.55 1

Pulasan 2.0 2

Rambutan 2.0 2

Rapeseed subgroup 20A 1.0 1 rapeseeds (canola)

Rice, grain 5.0 5 5 rice

Rice, hulls 20

Rice, straw 12

Rice, wild, grain 5.0 0.03 wild rice 5 rice

Rye, forage 7.0

Rye, grain 0.2 0.03 0.2

Rye, straw 1.5

Sapodilla 2.0 2

Sapote, black 2.0 2

Sapote, mamey 2.0 2
Page 70 of 75

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

Sapote, white 2.0 2

Sorghum, grain, forage 25

Sorghum, grain, grain 11 0.03 10

Sorghum, grain, stover 40 30 (dry wt)

Soursop 2.0 2

Soybean, hay 55.0 100 (dry) soybean 

fodder 

Soybean, hulls 1.0

Soybean, seed 0.5 0.5 0.5

Spanish lime 2.0 2

Spearmint, tops 30 30

Spice Subgroup 19B, except 

black pepper

38 38 

Star apple 2.0 2

Starfruit 2.0 2

Sugar apple 2.0 2

Sugarcane, cane 0.2 0.2

Sunflower subgroup 20B 0.5 0.5 seeds (calendula, evening 

primrose, jojoba, Niger, 

safflower, sunflower, 

tallowwood, tea oil plant 

0.5 sunflower seed

Tamarind 2.0 2

Tea, dried1 20.0

Tomato, paste 0.6 0.6

Tomato subgroup 8-10A 0.2 0.2 tomatoes

2 groundcherries, tomatillos

Turnip, greens 25

Vegetable, cucurbit, group 9 0.3 0.5 1 

Vegetable, foliage of legume, 

group 7

30.0 20 pea hay or pea 

fodder (dry) (dry 

wt)

Vegetable, leafy, except 

brassica, group 4

30.0 30 (except vine spinach) 5 celery

3 head lettuce

3 leaf lettuce

Vegetable, leaves of root and 

tuber, group 2

50.0

Vegetable, legume, edible 

podded, subgroup 6A, except 

soybean

3.0 0.02 edible podded 

(jackbeans, moth beans, 

runner beans, snap beans, 

soybeans, sword beans, wax 

beans, yardlong beans)

1.6 edible podded peas

3 legume vegetables

Vegetable, root, subgroup 1A 0.5 0.5 1 root and tuber 

vegetables (except 

potato)

7 potato Po

Vegetable, tuberous and 

corm, subgroup 1C

8.0 8 

Wasabi, dry 260

Wasabi, fresh 50
Page 71 of 75

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

Watercress 3.0 3

Wax jambu 2.0 2

Wheat, forage 15.0

Wheat, grain 0.2 0.03 buckwheat, wheat, 

triticale

0.2 wheat, triticale

Wheat, hay 30.0

Wheat, straw 10.0 15 straw and fodder 

(dry) of cereal 

grains (except 

maize and sorghum) 

(dry wt)

MRLs with NO US Equivalents

Carambola 0.1

Witloof chicory (sprouts) 0.3

*2.0 (of which not more than 0.1 is contained in the pulp)

1There are no United States registrations for use of azoxystrobin on coffee, green bean; ginseng; pear, Asian and 

tea, dried.

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.

§180.507 Canada Mexico2 Codex3

Livestock: (2) 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] 

(αE )-methyl 2-[[6-(2-

cyanophenoxy)-4-

pyrimidinyl]oxy]-α-

(methoxymethylene)benzen

eacetate, including the 

isomer

(Z )-methyl 2-[[6-(2-

cyanophenoxy)-4-

pyrimidinyl]oxy]-α-

(methoxymethylene)benzen

eacetate

Azoxystrobin

The residue is fat 

soluble.

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

US Canada Mexico2 Codex3

Cattle, fat 0.03

Cattle, meat 0.01 0.01 0.05 (fat)

Cattle, meat byproducts 0.07 0.01 meat byproducts of 

cattle

0.3 liver of cattle

0.07

Goat, fat 0.03

Goat, meat 0.01 0.05 (fat)

Goat, meat byproducts 0.07 0.07

Hog, fat 0.010

Hog, meat 0.01 0.01 0.05 (fat)

Hog, meat byproducts 0.010 0.01 meat byproducts of 

hogs

0.3 liver of hogs

0.07
Page 72 of 75

§180.507 Canada Mexico2 Codex3

Horse, fat 0.03

Horse, meat 0.01 0.01 0.05 (fat)

Horse, meat byproducts 0.07 0.01 meat byproducts of 

horses

0.3 liver of horses

0.07

Milk 0.006 0.006 0.01

0.03 milk fats

Sheep, fat 0.03

Sheep, meat 0.01 0.01 0.05 (fat)

Sheep, meat byproducts 0.07 0.01 meat byproducts of 

sheep

0.3 liver of ship

0.07

MRLs with NO US Equivalents

Eggs 0.01 0.01 (*)

Poultry meat 0.01 0.01 (*)

Poultry, edible offal of 0.01 liver of poultry 0.01 (*)

Fat of poultry 0.01
Page 73 of 75

Appendix F. Calculation of Inhalation Human-Equivalent Concentrations (HECs) and 

Human-Equivalent Doses for Azoxystrobin

The calculation of HECs accounts for pharmacokinetic (not pharmacodynamic) interspecies 

differences. HECs for residential and occupational scenarios were derived using the POD from 

the route-specific inhalation study and the regional deposited-dose ratio (RDDR). The RDDR 

accounts for the particulate diameter [mass median aerodynamic diameter (MMAD) and 

geometric standard deviation (GSD)] and estimates the different dose fractions deposited along 

the respiratory tract. Table F.1 summarizes the inputs used to obtain the diquat RDDR for HEC 

calculations.

Table F.1. Summary of RDDR Inputs for Azoxystrobin.

Study 

MRID

Species 

and 

Strain 

Animal 

Body 

Weight 

(g)1

Duration of Exposure

NOAEL 

(mg/L)

LOAEL 

(mg/L)

MMAD 

at 

LOAEL 

(μm)

GSD at 

LOAEL

Respiratory 

Region for 

Effect2

RDDR

hours/day days/week

49335202,

49335201

Han 

Wistar 

rats

270 6 5 0.0038 0.0112 3.5 2.71 ET 0.181

NOAEL = no-observed adverse-effect level. LOAEL = lowest-observed adverse-effect level. MMAD = mass median aerodynamic diameter. 

GSD = geometric standard deviation. RDDR = regional deposited-dose ratio.

1 Default Han Wistar rat body weight for combined sexes.

2 ET = extrathoracic, TB = tracheobronchial, PU = pulmonary, TH = thoracic, TR = total respiratory tract, ER = extrarespiratory (systemic). 

The POD from the route-specific inhalation study was adjusted for expected human exposure 

duration. Duration adjustment is performed based on Haber’s law, which assumes that a 

toxicological effect is proportional to the product of exposure level and duration. Animal-tohuman ratios of daily (hours/day) and weekly (days/week) exposures are applied to the animal 

inhalation study POD to result in a duration-adjusted animal POD for HEC conversion. For 

example, expected human exposure for occupational exposures is 8 hours/day and 5 days/week. 

Therefore, the adjusted NOAEL is 0.0029 mg/L.

NOAELadjusted =

0.0038 mg

L

×

6 hr/day

8 hr/day ×

5 days/week

5 days/week =

0. 0029 mg

L

For residential handler and outdoor post-application exposures, no duration adjustment was 

applied. For residential indoor post-application exposures, a duration adjustment to 7 days/week 

was applied with no daily exposure adjustment resulting in a duration-adjusted POD of 0.0027

mg/L. For residential bystander exposures, duration adjustments to 24 hours/day and 7 

days/week were applied resulting in a duration-adjusted POD of 0.0007 mg/L. 

The RDDR was applied to the duration-adjusted POD (except residential handler and outdoor 

post-application exposures with no duration adjustment where the RDDR is applied directly to 

the POD) to calculate HECs. Human-equivalent doses were subsequently calculated from the 

HECs for residential and occupational handler scenarios. The following equation describes the 

conversion from HECs to human-equivalent doses:
Page 74 of 75

The conversion to human-equivalent doses is an approximation involving the application of a 

conversion factor (CF) that takes into account the typical human volume respired per unit time. 

As the default breathing rate in the HEC calculation is 13.8 L/min for a typical human (body 

weight of 70 kg) under light activity conditions, the corresponding CF is 11.8 L/hr-kg. 

Absorption differences through the respiratory tract as compared to the oral route are expressed 

in the ratio “A.” In current practice, HED customarily assumes “A” to be unity (i.e., the entire 

animal orally administered dose is assumed to be absorbed via the inhalation route). Because the 

inhaled dose depends on activity level which directly impacts breathing parameters (at least until 

blood steady state levels are reached), the activity factor (AF) is a relative ratio that attempts to 

account for differences in respiratory rate due to activity level. Table F.2 lists the different 

exposure scenarios, the corresponding breathing rates associated with these activities, and the AF 

values that should be used for different occupational handler scenarios being assessed. Also 

listed in Table F.2 is the AF value assigned to residential handlers, which is assumed to be equal 

to occupational handlers in non-agricultural settings. The daily exposure duration (D) is 

equivalent to the “hours/day” value used in POD duration adjustment calculations. A summary 

of duration adjustments, HECs, and human-equivalent doses for all potential occupational and 

residential scenarios is presented in Table F.3. 

1 AF = Exposure scenario-specific human breathing rate (L/min) ÷ 13.8 L/min (the rate assumed in HEC calculation). Body 

weight is assumed to be 70 kg for all calculations.

Table F.2. Assigned Activity Factor (AF) Values Based on Different Handler Exposure Scenarios.

Exposure Scenario Human Breathing Rate

(L/min)

HED Calculation Inputs

AF1

Occupational

Pilots, tractor drivers 

(groundboom, airblast) 8.3 0.6

Mixer/loaders, lawn care 

operators (non-agriculture) 16.7 1.2

Handheld spray applications 

(e.g., backpacks, handgun, etc.) 29 2.1

Residential Handlers 16.7 1.2

Human-Equivalent Dose ≈ HEC (mg/L) × CF (L/hr-kg BW) × A × AF × D (hr/day)

HED = Human-Equivalent Dose (mg/kg BW/day).

HEC = Human-Equivalent Concentration (mg/L).

CF = Human-specific value that accounts for volume respired per unit time. CF equals 11.8 L/hr-kg based on the 

default-breathing rate assumed for a typical human (body weight of 70 kg) in the HEC calculation.

A = Absorption ratio through the respiratory tract as compared to the oral route – assumed to be unity. 

AF = Relative ratio that accounts for relative changes in respiratory rate due to activity level. Different AF values 

should be used for different occupational and residential scenarios.

D = Duration of daily exposure in hours: 8 hours assumed for occupational exposures; 24 hours assumed for 

bystanders/residential exposure; and 2 hours is often assumed for residential handler exposures.
Page 75 of 75

Table F.3. Summary of Inhalation Calculations for Human-Equivalent Concentrations and Doses for Azoxystrobin

Population Scenario

Toxicity Duration 

Adjustment

Human-Equivalent

Concentration

Human-Equivalent Dose

(mg/kg/day; breathing rate specific)

hours/day days/week mg/L mg/m3 8.3 L/min 16.7 L/min 29 L/min

Occupational Handler 8 5 0.00052 0.516 0.029 0.059 0.103

Residential

Handler NA NA 0.00069 0.688 NA 0.020 NA

Outdoor postapplication NA NA 0.00069 0.688 NA NA NA

Indoor postapplication NA 7 0.00049 0.491 NA

Bystander 24 7 0.00012 0.123 NA

NA = not applicable (the expected duration of the exposure scenario is less than the duration of available inhalation toxicity 

studies; downward adjustments are not permitted).