### UNITED S TATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON

, D.C. 20460

OFFICE OF
CHEMICAL SAFETY AND

POLLUTION PREVENTION



### MEMORANDUM

Dat e: Dec e mb e r 4

, 2015



### SUBJECT: Azoxystrobin: Hum a n H ea lth Draft Ri s k Assess m e nt fo r R eg i s tr a ti o n Review

P C Code: 1 2 8810

Decision No.: 511551

P e titi on No.: NA DP Ba r code : 0430443

R eg i s tra tio n No.: NA
Regulator y Action: Re g i st ration R ev iew

Case No.: 7245 Ri s k A ss ess m e nt T y p e: Agg r egate Risk Assess m ent

TXR No.: NA CAS No. : 1 3 1 860-33-8

40 CF R : § 180.507 MRID No.: NA



### FROM:

THROUGH:

TO: Kristin Ru ry, Bi o l og i s t 

# ¥-**~** /J,f' /

# · C

_ Whang Phan g, Se ni or

## To**icol ~~** **~ ~**  -- Meheret Neg ussic

, Chemi s t 

### lf e/.e.,,-ef-**μe~** Ri s k Ass ess m e nt Branch 3 (RA B 3)

H ea lth Effec t s Div i sion (7509P)

# i~**th y**  C

. Dole

, I ndustria l Hygien i st -;--

# ~ C •

# ~ Risk Assess m e nt and Sc i e nce S upport Branch (RASS B{'

A ntimicrobi a l s Di v isi o n

# ~i**tin e**  Otinger

, Branch C hi ef

# ~/j Ri s k Assessment Branch 3 (RA B 3) 

# /#._

-

...



# _ _ _..;....



# _ _ _ Health Effects Division (7 5 09P)

Veronica Dut c h

, Ri sk Manager R eviewer

Jill B l oom
, T ea m Leader

Pesticide Re-evaluation Divisi o n ( PRO ) (7508P)

As part of R eg i s tration Revi ew, PRD of th e Office of Pesticid e Pro grams (O PP ) ha s requested

that HED evalua t e the h azard and ex posur e d a t a and conduct occ up ationa l a nd r es id e ntial

exposure assessments, as n eeded

, to es tim a t e the risk to human health that w ill r es ult fro m the

curre ntl y re g istered u ses of p es ticide s. This memorandum se r ves as H E D 's dra f t hum a n he a lth

risk assessme nt of th e dietary, occupational, and re s id e ntial exposure; a nd aggrega t e risk from

Pa ge 1 of 75

### the registered uses of azoxy s trobin. The most recent quantitative human health risk a ssess ment

was performed in 2015 (K. Rury

, 0423691 and 0418374

, 04 / 07 / 2015). The following risk

assessment updates have been made:

• A route-specific inh alation toxicity study using formulated azoxystrobin was incorporated into the toxicity database and selected for inhalation risk assessment;

• The re gistered antimicrobial uses of a z oxystrobin have be e n r eeva luated according to

current policies;

• Th e registered re s idential u ses of azoxystrob in hav e be e n 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 exposu r e assessment for the regist e red uses was completed r e flecting

recent update s to the azoxy s trobin risk a ssess ment po int s of departure

, HEO's SOPs

, and policy changes for body we i ght assumptions.

A summary of th e findings and an assessment of human r i sk resulting from the registered us es of azoxystrobin are provided in thi s 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 Tole rance 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 Ris k

................................ ...................... 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 Azoxyst robin 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 Charac terization

................................ ................................ .. 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 Append ix 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 ) ha ve conducted a

human health draft risk assessment (DRA) to evaluate all existing registrations o f 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 a nd greenhouses. Azoxystrobin is also registered for use on bananas, plantains, citrus, and tuberous and corm vegetables as a post

harvest treatment. Azoxystrobin may also be used on golf course turf, lawns, sports fields, ornamentals, conifers, roses, cu t 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

vege tables, 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; sunflo wer; 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, chemi gation, 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 persona l 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

- for mulations 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 expo sed to a zoxystrobin 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, applica tors 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 al so 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 paren tal 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 incide ntal 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 inhal ation toxicity study in rats with the soluble concentrate (SC) formulation of azoxystrobin

. For inhalation exposures, t he 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. A n

a dditional 10 X is applied for a database uncertain ty factor to account for the requirement for an

inhalatio n toxicity study on the technical active ingredient (a.i.) because the available 28

- day inhalation study was test ed on only approximately 8% a.i., whereas most of the marketed

p roducts contained 30

- 50% a.i . Therefore, the level of concern (LOC) for inhal ation 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 ad verse 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,

m agnitude 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

- level s 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

. Th e chronic assessment was based on the assumption of tolerance

- level

residues for all commodities

, average percent crop treated ( %CT ) estimate s 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 analys i s.

A cute and chronic dietary exposure and risk estimates are below HED’s LOC for the U.S. population and all population subgro ups. Combined acute dietary exposure from food and drinking water at the 95 th 

### 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 acu te dietary exposure is children 1

- 2 y ea rs old , with an estimated exposure at the 95 th


### percentile equivalent to 40% of the aPAD.

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

f or the general U.S. population and 15% of the cPAD for children 1

- 2 y ea rs 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

Resident ial SOPs 1 

### ( 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 r esult 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. T he

inhalation PO Ds 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 azoxy strobin

treated paint and for applying mold spray. The M OE s 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

- procedures

residential

- pesticide

### Page 8 of 75

vinyl f looring , 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 surfac e directed mold

sprays.

Non

- Occupational Spray Drift Assessment A quantitative spray drift assessment for azoxystrobin is not required because the max imum application rate to a crop/ta rget site multiplied by the adjustment factor for drift of 0.26 is l ess than the maximum direct spray residential turf application rate of 0.99 lb ai/A 2 

### for any azoxystrobin products . The turf post

- application MOEs have been previously assessed and are based on the revised SOPs for Residential Exposure Assessment.

Aggr egate 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 di ffer from those seen in the short

term oral toxicity studies used for aggregate assessment. For children 1 to <2 years, the short

term aggregate risk estimates are not of concern; the margin of exposure (MOE) is 300 for children 1 to < 2 years old

.

Occ upational 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 agric ultural, 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. P ost

- 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

- applicatio n assessment wa s 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 a zoxystrobin 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 pain t 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 i s an EPA

- registered pesticide product; the paints

themselves are not EPA

- registered pesticide products and thus are not required to bear pesticide labeling

.

Environmental Just ice 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 an d 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 rev iew 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

sat isfied.

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 inhalati on 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 th at study, a database uncertainty factor will be appl ied 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) M ethod, RAM 243/04, is availab le for the enforcement of tolerances for residues of azoxystrobin and its Z

isomer in crop commodities. The method has undergone method validation by the Analytical

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 r evised 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 rec overed 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

Tole rance 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 0.3 0

Cottonseed subgroup 20C 0.7 0.7 0

Ginseng 1 0.5 0.5 0

Pea and bean, dried shelled, except soybean, subgroup 6C 0.5 0.5 0

Pea and bean, succulent shelled, subgroup 6B 0.5 0.5 0

Peanut 0.2 0.2 0

Peanut, refined oil 0.6 0.6 0

Rye, grain 0.2 0.2 0

Soybean, seed 0.5 0.5 0

Sugarcane, cane 0.2 0.2 0

Sunflower subgroup 20B 0.5 0.5 0

Tomato, paste 0.6 0.6 0

Tomato subgroup 8

- 10A 0.2 0.2 0

Vegetable, root, subgroup 1A 0.5 0.5 0

Wheat, grain 0.2 0.2 0

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; t he US and the

Canadian residue definition s include both the predominant E isomer and the minor Z isomer

whereas t he Codex includes only the E isomer.

Th ere are Codex and Canadian maximum residue limits ( MRLs ) established for residues of azoxystrobin. The US and Codex MRLs are in harmony on subgroup s 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 n ot harmonized with Codex. T he 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/revis ions 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 tox icity 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 residentia l/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 recomme nded 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 curr ently 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. Azoxystrobi n 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 /20 15 ).

3.1 Chemical Identity

Table 3.1

. Azoxystrobin Nomenclature.

Compound

Common name Azoxystrobin

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

IUPAC name methyl ( 2 E )

- 2

- {2

- [6

- (2

- cyanophenoxy)pyr i midin

- 4

- yloxy]phenyl}

- 3

- methoxyacrylate

CAS name methyl ( α E )

- 2

- [[6

- (2

- cyanophenoxy)

- 4

- pyrimidinyl]oxy]

- α

- (methoxymethylene)

- benzeneacetate

CAS registry number 131860

- 33

- 8

End

- use products (EP) Abound® F lowable Fungicide (EPA Reg No. No. 100

- 1098 ) containing 22.9% ai

Regulated metabolite, Z

isomer

Common name Azoxystrobin, Z

- isomer

Company experimental name R230310

Chemical name methyl ( 2 Z )

- 2

- {2

- [6

- (2

- cyanophenoxy)pyr i midin

- 4

- yloxy]phenyl}

- 3

- methoxyacrylate



### 3.2 Physical Chemical Properties

Azoxystrobin has a log octanol/water partition coefficient (log P
ow 

### ) of 2.5 and is considered relatively insoluble in water. However, azoxystrobin has a molecular weight of 403 g/mol;

### 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 pene tration 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 Azoxystrobin 1

.

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;

Watercre ss 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 Azoxystrobin 1

.

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 C orm 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 Azoxystrobin 1

.

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 Pour Liquid 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 ad ult and children may be exposed following application. T here is a potential for spray drift that may

result in exposure s 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, "Feder al Actions to Address Environmental Justice in Minority Populations and Low

- Income Populations," ( http://www.epa.gov/environmentaljustice/resources/policy/exec_or der_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 ethni c 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 pr oducts 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 exposure s 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 po ints of departure for the risk assessment. A detailed discussion

of certain POD selection s (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 ha s 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 depart ure 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

 D ermal penetration study in rats

HED recommended that t he required i mmunotoxicity study not be required based on the evaluation of entire toxicity data set which indicated no potential for immunotoxicity ( TXR

00570 7 1 ).

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

Following oral administration azoxystrobin was absorbed and distributed broadly. B iliary

excretion data suggested that approximately 70% of administered dose was absor bed 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 kidn eys. Less than 0.5% of the

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


### 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 biotransf

ormation 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 Abso rption

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 admi nistered 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 d ecreased 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 toxic ity 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 need ed (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 (non

linear, slight bu t 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

con siderations:

 

### 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 az oxystrobin.

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) for mulation 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 azoxystr obin formulations available in the market contain 30 to 50% azoxystrobin. Therefore, HED recommends requiring an inhalation toxicity study on technical azoxystrobin. In absence of th at study, a database uncertainty factor is to be apply for assessing inh alation 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

neurot oxicity 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 expo sure assessment s 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 expecte d 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 azoxyst robin, 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 selection s (acute and chronic dietary , dermal, and incidental oral ) is presented in the previous azoxystrobin risk assessment s (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 int ermediate 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 aero dynamic 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 calculate d 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 c onventional 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 breat hing 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 addi tional 10X uncertainty factor is applied for a database uncertain ty 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 handler s 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 uncer tainty).

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 Table s 4.5. 1 and 4.5.2.

Table 4. 5 .1. Summary of Toxicological Doses and Endpoints for Azoxystrobin for Use in Dietary, Non

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 Toxic ological Effects

Acute Dietary (All Populations) LOAEL = 200

mg/kg/day UF A = 10X

UF H = 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 UF A = 10X

UF H = 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 Short

Term (1

- 30 days) &

Intermediate

term (1

- 6 months) NOAEL = 35

mg/kg/day UF A = 10X

UF H = 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).

Inhalation 2
(All

Durations ) Rat inhalation

NOAEL=3.8 μg/L

UF A =3

UF H =10 FQPA SF =

UF DB =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 : HEC 3 = 0.688 mg/ cubic meter

HED 4 =0.02 mg/kg/day
(16.7 L/min)
Antimicrobial

Residential Uses ++ : HEC 3 = 0.516 mg/ cubic meter

HED 4
= 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 o bserved adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human

### Page 23 of 75 (interspecies). UF H = 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 = le vel 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 re commend ed. 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 ( V entilation rate = 16.7 LPM).

Table 4. 5

. 2. Summary of Toxicological Doses and Endpoints for Azoxystrobin for Use in O ccupational

Human H ealth 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).

Inhalation 2
(All

Durations ) Rat inhalation

NOAEL=3.8 μg/L

UF A =3

UF H =10

UF DB =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

HEC 3 = 0.516 mg/ cubic meter

HED 4 ( 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 obse rved

ad verse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = 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 = le vel 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 specif ic conversion factor*daily duration +: An inhalation study on active ingredient (a.i.) is re commend ed. This safety factor is to account for lack of a study with the a.i.

++: Three v entilation rate s corresponding to three HEDs used for assessing occupationa l 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. A lthough a zoxystrobin is registered for use in residential areas

, the

inhalation and incidental oral PODs are based on the different effects seen in different route

specific studies; therefore, exposures from these routes should not be combined . No dermal hazard was identified in the azoxystrob in database; therefore dermal exposures are not evaluated or combined with any other exposure route for occupational and residential handlers and post

application scenarios and non

- occupational spray drift assessments.

### Page 24 of 75 4.5.3 Cancer Classification and Increa sed 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 an d 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 targ et 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, de velopmental 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 existin g 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 pes ticide 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 m aking 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 throug h 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

tes ting 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, 2013 4 

### and 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 ED SP, 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 dietar y 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 Azoxystrobin 1

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. H ED 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 s ignificant. 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 f ound 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 highes t registered application rate (0.55 lb ai /A, 9 applications per year with a 10

- day interv al 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 cons ervative 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 W ater (μg/L) (Acute/Chronic)

Peak (1

- in

- 10 yr) 365

- day

Average (1

- in

- 10 yr) Entire

Simulation

Mean SCI

- GROW 2

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 re e valuated he re 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 . T he assumptions of the dietary

assessment included tolerance

- level residues for a ll 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 Co mmodities 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 ) estimate s 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 applicat ion scenario was incorporated directly into the dietary assessment s (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, t he 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%; cau liflower, <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%; onion s, 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 see d (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 95 th 

### 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 ex ceed the Agency’s level of concern (< 100% of the aPAD) for the U.S. population and all subgroups. T he chronic dietary (food and drinking water) risk estimates utilized 6.0% of the chronic population adjusted dose (cPAD) for the U.S. population and

utiliz ed 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 Azoxystrobin 1

.

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 i ndirect 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

dietar y 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, D 430444 , 12/ 04 / 2015).

6.1 Residential (Non

- Occupational) Handler Risk

6.1.1 Residential Handler Risk

– Conven tional 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 eac h 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. In termediate

- 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 SOPs 6



### .

For residential handlers, exp osures 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. Addit ionally, combining exposures to these uses is not considered appropriate in light of the already conservative assumptions inherent in the assessment. For example, w hen 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. E xposure 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 azoxystr obin

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 s prayer 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 Esti mates for Azoxystrobin

.

Exposure Scenario Formulation Inhalation Unit Exposure (mg/lb ai) Maximum

Application Rate 1 Area Treated

or Amount

Handled Daily 2 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

- procedures

residential

- pesticide

### Page 30 of 75

Table 6 .1.1. Residential Handler Non

- cancer Exposure and Risk Esti mates for Azoxystrobin

.

Exposure Scenario Formulation Inhalation Unit Exposure (mg/lb ai) Maximum

Application Rate 1 Area Treated

or Amount

Handled Daily 2 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/ft 2 1000 ft 2 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/ft 2 1000 ft 2 0.0000060 3,300

Belly Grinder to Turf

Granules 0.039

0.0000218 lb ai/ft 2 1200 ft 2 0.000013 1,600

Spoon around Gardens/Trees 0.087 1200 ft 2 0.000028 700

Spoon to Turf 0.087 100 ft 2 0.0000024 8,400

Cup around Gardens/Trees 0.013 1200 ft 2 0.000043 4,700

Cup to Turf 0.013 100 ft 2 0.00000035 56,000

Hand Dispersal around

Gardens/Trees 0.38 1200 ft 2 0.00012 160

Hand Dispersal to Turf 0.38 100 ft 2 0.000010 1,900

Shaker Can around

Gardens/Trees 0.013 1200 ft 2 0.0000043 4,700

Shaker Can to Turf 0.013 100 ft 2 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/standard

operating

- procedures

- residential

- pesticide ).

3

. Inhalation Dose = Inhal ation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre

, gal , or ft 2 ) × Area Treated or Amount Handled (A

/day, gallons/day , or ft 2 /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 Pai nt 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 MOE s 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 prote ction 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 applicator s. 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 3 00 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

Rate 1 Amount Paint

Applied (lb/day) 2 Amount

Ai

Handled (lb/day) Unit

Exposure (mg/lb ai) 3 Daily Dose 4

(mg/kg/day) Inhalation

MOE 5
(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) / D aily 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

Rate 1
(% a.i.) Amount

Product Applied per Day 2 Amount Ai

Handled 3 (lb/day) Unit

Exposure 4 (mg/lb ai) Daily Dose 5

(mg/kg/day) Inhalation

MOE 6
(LOC = 300)

L ow Pressure

H andwand 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)]/ Bod y 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 ha s 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 SOPs 7



### . While not the only

life stage 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

SOPs Error! 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 th e 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 o verly

- 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 use d 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 post

application incidental oral exposures.

Table 6.2.1. Residential Post

- applic ation Non

- cancer Exposure and Risk Estimates for the Conventional Uses of Azoxystrobin.

Lifestage Post

- application Exposure Scenario Application Rate 1 Dose (mg/kg/day) 2 MOEs 3 Use Site Route of Exposure

Child ren 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

7 Available : http://www2.epa.gov/pesticide

- science

- and

- assessing

- pesticide

- risks/standard

- operating

- procedures

residential

- pesticide

### Page 33 of 75

Table 6.2.1. Residential Post

- applic ation Non

- cancer Exposure and Risk Estimates for the Conventional Uses of Azoxystrobin.

Lifestage Post

- application Exposure Scenario Application Rate 1 Dose (mg/kg/day) 2 MOEs 3 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 label s (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

- pesticide

risks/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 /impregn ated 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 in to materials, modifications were made to the surface residue equations to include an availability factor (AF) of 0.5 percent 8 

### to 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

. T he MOE is 610 and the risk is not of concern.

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

. Application Rate (percent by weight) Surface

Residue 1 (mg/cm 2 ) Transfer

Factor Hand

Residue 2 (mg/cm 2 ) Exposure 3

(mg/day) Dose 4

(mg/kg/day) Incidental

Oral MOE 5

0.225 0.0044 1.0 0.0044 0.65 0.057 610

1

. Surface Residue (SR) = Density (1300 mg/cm 3 ) * Vinyl Thickness (0.3 cm) * W eight F raction (AR/100) * A vailability F actor (0.5/100)

2

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

3

. Exposure = HR (mg/cm 2 ) * F M (0.13) * SA H (150 cm 2 ) * 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 carpe t

8 The availability factor is based on migration calculations using Fick’s 1 st and 2 nd 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 post

application risk assessment. Each assumption, factor, and algorithm is detailed in the 2012

Residential SOPs 9



### . The MOEs for post applicatio n 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 assess ing 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

expo sure 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 (3 0

- 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 Rate 1 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/ft 2 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 label s (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

- pesticide

risks/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
dur ations 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 SOPs 10



### . The MOE for incidental oral hand to mouth exposure to azoxystrobin treated t oys is summarized in Table

9 http://www2.epa.gov/pesticide

- science

- and

- assessing

- pesticide

- risks/standard

- operating

- procedures

- residential

pesticide

10 http://www2.epa.gov/pest icide

- science

- and

- assessing

- pesticide

- risks/standard

- operating

- procedures

- residential

pesticide

### Page 35 of 75

6.2.2.3

. T he 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

Residue 1 (mg/cm 2 ) Object Residue 2

(mg/cm 2 ) Exposure 3

(mg/day) Dose 4

(mg/kg/day) Incidental Oral

MOE 5
(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 cm 2 )

2

. Object Residue (OR) = SR (mg/cm 2 ) * Transfer Factor (1.0)

3

. Exposure = OR (mg/cm 2 ) * S urface A rea M outhed (10 cm 2 ) * E xposure T ime (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 aggrega te 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. T herefore, 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 Post

application MOE 3 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. C hildren 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).



### S ince 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 A gency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fu ngicide, 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 develope d a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis ( http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219 ). During Registrat ion Review, the agency will utilize this analysis to determine if data (i.e., flux studies, route

- specific inhalation toxicological studies) or further analysis is need ed 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 moveme nt 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 off

target and can lead to exposures to those it may directly contact. They can al so 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 dr ift 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 expos ures 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

t urf 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 exis ting 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 pathwa ys.

### Page 37 of 75

that would be associated with spray drift. It should be noted that t he registered residential uses on turf re sult 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 app lication 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 im mediately 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

b ecause the max imum application rate to a crop/ta rget 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/A 12 

### for any azoxystrobin products . The turf post

- applicati on 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

estimate s for the U.S. population and all other population subgroups, resulting from aggregate exposure to azoxystrobin in food and drinking water

, are bel ow the Agency’s LOC . The food and drinking water exposure estimates are 1 6 % of the aPAD for the general U.S. population, and

4 0 % 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 expo sure 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 (prim ary) routes.

T he 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 a re 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 agg regate 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 Aggregat e Risk Calculations.

Population Short

- and Intermediate

- Term Scenario s

NOAEL mg/kg/day LOC 1 Max

Allowable Exposure 2 mg/kg/day Average

Food and

Water Exposure mg/kg/day Residential

Exposure mg/kg/day 3 Total

Exposure mg/kg/day 4 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 assessmen t, 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 aggre gate 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 t o 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 no t 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 azoxys trobin 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

r eleased 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

- pesticide

risks/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 Ou tdoor 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.

Fo r 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 appl icable 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 includi ng 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 r espirators 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 inhalati on 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 ap plication 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 acreage 13 

### 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 h igh 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 ap plications;

 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, la ndscaping, 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, nurs ery 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 flow able formulations in an automated system for post

- harvest
treatment of bananas,

 Mixing/loading liquids in an automated system for post

- harvest treatment fo r 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 vegeta ble, 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 tre ated 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 a re 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 l iquids 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

p ressurized 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 potat o, 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 recen t (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 th e 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 applica tors , 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 inter ior 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 3 00 (i.e. the target MOE) for paint manufacturing w ithout respirators w hich 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 i nclude 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 ref erred to as re

entry 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 var y 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 p ost

- 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 vol atilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html ). The agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis ( http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

OPP

- 2014

- 0219 ). During Registration Review, the agency will utilize this analysis to determine if data (i.e., flux studies, route

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

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 requireme nts 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 faciliti es. 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, unli ke 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 d irectly involved in the automated treatment process, there is potential for indirect inhalation exposure.

### Page 44 of 75

Exposures for these various scenari os 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 trigger ing 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 tim e 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 year

round to the registered cr ops. Additionally, the occupational inhalation POD is applicable to both durations; t herefore 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 continu ous 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 post

application inhalation MOEs for th e 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 occupation al 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 hou rs 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 post

application exposures to azoxystrobin.

For A zoxystrobin P roducts 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 Registra tion (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

B oth 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 consulte d 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 rep ort. 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 drift 15 

### 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 re latively 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

- wps

interim

- restricted

- entry

15 SENS OR

- Pesticides defines drift as “off target movement of a pesticide” which includes volatilization.

### Page 46 of 75

1 2 .0 References

G. Dannan

. 09/25/2000; HED Doc No. 014329. AZOXYSTROBIN

- Report of the Hazard

Identificat ion Assessment Review Committee.

E. Evans; 12/02/2015 ; D 430445. Azoxystrobin : Tier I Revi ew 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 Conver sions 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 Dri nking 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#4E83 19) and Crop Group Conversions for Stone Fruit Group 12

- 12 and Tree Nut Group 14

- 12.

J. Leshin; TXR#00 57242

. Azoxystrobin

- Report of the Hazard and Science Policy Council (HASPOC) Meeting of September 3, 2015 : Recommendations on the Need for a Subchronic Inhalation Toxicity stud y.

J. Leshin, 11/13/2014, TXR#0057071. Azoxystrobin: Summary of the Hazard and Science Policy Council (HASPOC): Recommendations on the Requirement of a n Immunotoxicity Study.

K. Rury. 04/07/201 5 , 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 asse ssment also includes updates to the Stone Fruit Group 12

- 12 and Tree Nut Group 14

- 12 Crop Groups.

K. Rury. 12/4 /2015, D 430444 . 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

A ppendix 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 CR 1 yes

yes

yes

no

n o *

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 -

-

-

1 CR = Conditionally Required

* A subchronic inhalation toxicity study with the TGAI is re commend ed (TXR# 0057242 )

** The immunotoxicity study is not required (TXR#0057071)

### Page 49 of 75

A.2 Toxicity Profile s

Table A.2.1

. Acute Toxicity Data on Technical Azoxystrobin

. Guideline

No. Study Type MRID # Results Toxicity Category

870.1100 Acute Oral

- Rat 43678122 LD 50 > 5000 mg/kg (Limit Test) in Males &

Females IV

870.1200 Acute Dermal

-

Rat 43678124 LD 50 > 2000 mg/kg (Limit Test) in Males &

Females III

870.1300 Acute Inhalation

-

Rat 43678126 LC 50 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

anothe r. 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 incr eased severity of effects (atrophy of ventrolateral respiratory epithelium and increased

incide nce 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

. Offs pring 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

mutati on 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 ce ll 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 S

9 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 μ g/mL

- S9; 100

- 200 μ g/mL +S9) that were moderately to

severel y 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 sexe s.

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%

ab sorption 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/cm 3

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, pK

a Not dissociable

Octanol/water partition coefficient, Log(K OW ) 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 applicabl e 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

website 16



### .

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 Azoxystrobin 1

.

Exposure Scenario Crop or Target 1 Maximum
Application Rate 2 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 Azoxystrobin 1

.

Exposure Scenario Crop or Target 1 Maximum
Application Rate 2 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 Azoxystrobin 1

.

Exposure Scenario Crop or Target 1 Maximum
Application Rate 2 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

N/A Landscaping (Plants, Flowers, Trees, 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

N/A Golf Course (Tees, Greens, Fairways) 0.95 lb ai/A 24 120 240

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 Azoxystrobin 1

.

Exposure Scenario Crop or Target 1 Maximum
Application Rate 2 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 re gistered application rates and applicable exposure scenarios to cover all registered use sites. Shaded MOEs represent risk estimat es 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

Table 17 ”, which, along with additional information on HED policy on use of surrogate data, including descriptions of the various sou rces, can be found at the Agency website 18

. Area or Amount Treated Information is available in ExpoSAC P olicy 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 Rate 1 Inhalation MOE (LOC = 300)

lb ai/gal solution Baseline 5 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

Bananas 2 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

Bananas 2 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/o pp00001/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 protectio n. “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,

Wa tercress, 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 0.000004 1 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 P olicy 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 de fault 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/d ay) = 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 P olicy 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 de fault 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/d ay) = 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. S haded 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 respira tor). 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 lo ader/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 P lanted 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 exposu res. 3 HED default for lb seed treated/planted per day from HED Exposure Sc ience 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)

Baseline 4 PF5 4 PF10 4 EC 4 Baseline 5 PF5 5 PF10 5 Engineering

Control 5

Loader/Applicator, Sewer, Bagger, Multiple A ctivities

Peanuts 0.00008 0.043 0.00024 339,500 0.01 5 0.0029 0.0015 0.0015 4 20 40 40

Planters

Peanuts 0.00008 1.69 N/A 228 0.0006 2 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)

Baseline 4 PF 10 4 Engineering

Control 4 Baseline 5 PF 10 5 Engineering

Control 5

Loader/Applicator, Sewer, Bagger, Multiple A ctivities

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

Rate 1 Amount Paint

Manufactured or Applied (lb/day) 2 Amount Ai

Handled (lb/day) Unit Exposure

(mg/lb ai) 3,4,5 Daily Dose 6

(mg/kg/day) Inhalation

MOE 7
(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 Surrog ate 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: T

shirt/NG = t

- shirt and no gloves; NR = no respirator.

3 . Inhalation Dose = [U nit E xposure (μg/% ai) * A pplication R ate (% ai in solution) * A djustment F actor (0.001 μg/mg)] ÷ B ody W eight (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 MOE 3

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) 3 Inhalation MOE 4 (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)] ÷ Bod y 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 Mexico 2 

### Codex 3

§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 Mexico 2 

### Codex 3

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 Mexico 2 

### Codex 3

Bushberry subgroup 13

- 07B 5.0 3

4 gooseberries 5.0 (Berries & other small fruits, except cranberry, grapes and strawberry) Caneberry subgroup 13

- 07A 5.0 5

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 bean 1 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 grape s

Fruit, stone, group 12 1.5 2 2 Ginseng 1 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 Mexico 2 

### Codex 3

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 E nglish 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, Asian 1 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 Mexico 2 

### Codex 3

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, dried 1 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 Mexico 2 

### Codex 3

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)

1 There 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 Mexico 2 

### Codex 3

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] (α E )

- 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 Mexico 2 

### Codex 3

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 Mexico 2 

### Codex 3

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 de posited

- 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 summari zes 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 ( μ m) GSD at

LOAEL Respiratory

Region for

Effect 2 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 t ract, 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

- to

human ratios of daily (hours/day) and weekly (days/week) exposures are applied to the animal inhalation study PO D to result in a duration

- a djusted 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.

NOAEL adjusted 

### = 0

. 0038 mg

L × 6 h r / day

8 h r / day × 5 d ays / week

5 days / week = 0

. 0029 mg

L

For residential handler and outdoor post

- application exposures, no duration adjustment was applied. For reside ntial indoor post

- application exposures, a duration adjustment to 7 days/week was applied w ith 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 an d 7 days/week were applied resulting in a duration

- adjusted POD of 0.0007 mg/L.

The RDDR w as 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 fr om 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 calcula tion 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 cur rent 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 (a t 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 brea thing 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 occ upational 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 oc cupational 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

AF 1

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 han dler exposures.

### Page 75 of 75

Table F .3. Summary of Inhalation Calculations for Human

- Equivalent Concentration s 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/m 3 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 post

application NA NA 0.00069 0.688 NA NA NA

Indoor post

application 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).