D ate:

S ubj ec t : 

### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON

, D.C. 20460

Ju l y 25, 20 1 4 OFFICE OF C HEMICAL S AFET Y AND POLLUTION PREVENTION

I s of e t a mi d. Occupationa l and R es i dentia l Expo s ure and Ri s k A ssess m e nt for the Propo sed New U ses of th e New Act i ve Fu n g icid e, i ncluding Agricultural U ses on A l mond s, L e ttu ce, Small Vine C l imbing Fruit s (Crop S u b g roup 13

- 07F)

, Low Growing Berrie s (Crop Subgroup 13

- 07G), and Rap esee d (C rop Subgroup 20A); and U ses on Turf grass ( includ in g Golf Courses, Sod Farm s, Seed Farm s, Re c r ea tiona l Fi e ld s, and Commercia l /Re s identia l Lawn s).

P C Co d e: 270000 DP Ba r co d e: 0 4 1 1 113 D ecisio n No

. : 474283 Regu l ato r y Actio n : Section 3 Case No.: NA Pet i t i o n No

. : 3 F 8 1 42 Reg i st r at i o n N os.: 7 1 512-ER, 715 1 2- EE

, 71512-EG R isk Assessme n t Ty p e: O cc u pationa l /R es id e nt i al Exposure Assess m e nt T X R No.: NA CAS No

. : 8759 1 5-78-9 MR ID No.: NA



### Fro m :

T hrou g h:

To:

I ntro du c t i on Nancy J. Keller

, Chemist Ri s k Assessment Branch 3 H e al th Effects Di v i s ion (7509P) 40 CF R : to be determined



# ---

Barry 

### 0' Ke efe, S e nior Biologi s t
, ORE Team Le a der /]( 

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Ri s k A ssess m en t Branch 3 (RAB3) 

## r**~** H ea lth Effects D i vision (750 9 P)**~** 

# fi

and 

### /l/

,

## ~ Matthew Llo y d

, Indu st r i al Hy g i e ni st · 

### I
Al exa ndra LaMay

, Bio l ogist '{ : 

## -cv v'(l'· )/ Expo s ur e Science Advi so r y Committee (ExpoSAC) Hea l th Effe cts Divi s ion (7509P)

Heather Garvie/Tony Ki s h

, RM #22 Fung i cide Bra n c h (FB) Divi s ion ( 7505P)

The R eg i s tration Division (R D ) reque s ted that the H ea l th Eff ects Di v i s i on (HED) co nduct an occupationa l and r esi d e nti a l ex po s ure and ri s k assessment for all of the propo se d new u ses o f th e

n ew act ive fungicide, i s ofetamid

, including agricultural u ses on almonds, lettuce, s ma ll vine climbin g fruits (crop s ubgroup 13-07F)

, low g rowing b e rri es (cro p s ubgroup 13

- 07G)

, and

Pag e 1 of22rapeseed (crop subgroup 20A); and u ses on turf grass (including golf courses , sod farms, seed farms, recreational fie ld s, and commercial/residential l awns)

.

I t is HED po li cy to use the best available data to assess exposure

. Several sources of generic data were u sed in this assessment as su rrogat e data in the absence of chemical-specific data

, includin g Pest i cide Handler s Exposure Databa se Version 1.1 (PHED 1. 1 ); the Agricu l tura l Hand l er Exposure Task Force (AHETF) database; the Outdoor Residential Exposure Task Force (ORE TF) database; the R es id en tial SOPs (Lawns/Turf)

. Some of these data are proprietary

, and

s ubj ect to the data protection provisions of the Federal Insecticide

, Fungicide

, and Rod e nti cide Act (F IFR A).

Note: Thi s memorandum was r ev i ewe d by the Exposure Science Advisory Committee (ExpoSAC) on July 24, 2014.

Page 2of22

### Page 3 of 22 Table of Contents

1.0 Executive Summary

................................ ................................ ................................ ............. 4 2.0 Risk Assessment Conclusions and Recommendations

................................ ........................ 6 2.1 Summary of Risk Estimates

................................ ................................ ............................. 6 2.2 Label Recommendations

................................ ................................ ................................ .. 7 2.3 Data Deficiencies and Requirements

................................ ................................ ............... 7 3.0 Hazard Characterization

................................ ................................ ................................ ....... 7 4.0 Use Profile

................................ ................................ ................................ ......................... 10 5.0 Residential Exposure and Risk Estimates

................................ ................................ .......... 11 5.1 Residential Handler Exposure/Risk Estimates

................................ ............................... 11 5.2 Residential Post

- Application Exposure/Risk Estimates

................................ ................. 13 5.3 Residential Risk Estimates for Use in Aggregate Assessment

................................ ...... 15 5.4 Spray Drift

................................ ................................ ................................ ...................... 16 5.5 Residential Bystander Post

- Application Inhalation Exposure

................................ ....... 16 6.0 Occupational Exposure and Risk Estimates

................................ ................................ ...... 17 6.1 Agricultural Occupational Handler Exposure/Risk Estimates

................................ ....... 17 6.2 Occupational Post

- Application Exposure/Risk Estimates

................................ ............. 20 6.3 Restricted Entry Interval

................................ ................................ ................................ 21 Appendix A. Summary of Occupational Handler Non

- Cancer Algorithms

................................ 22

### Page 4 of 22

1.0 Executive Summary

Isofetamid is a new active ingredient (ai) cu rrently undergoing joint review with the Pesticide Management Regulatory Agency (PMRA) in Canada

. It has been developed by ISK Biosciences Corporation (ISK) , with a proposal (PP# 3F8142 ) for one technical product and two end

- use product (EP) registrations in the United States. The proposed uses inc lud e agricultural food

- uses and commercial/residential tur f uses.

Isofetamid is a systemic, broad spectrum fungi cide belonging to the thiophen e class of chemistry. Isofetamid is a phenyl

- oxo

- ethyl thiophene amide that acts as a succinate dehydrogenase inhibitor (SDHI) , which causes adverse effects in plant and fungi respiration

. Proposed Use Profile The agricul tural uses include broadcast foliar treatment to various crops including almonds, lettuce, small vine climbing fruits (crop subgroup 13

- 07F), low growing berries (crop subgroup 13

- 07G), and rapeseeds (cro p subgroup 20A). The turfgrass uses include broadcast foliar treatment to various sites, including residential lawns

. Both EPs are suspension concentrate (SC) formulations containing 36.0% ai, by weight (3.33 lb ai/gal). The proposed application rates

r ange from 0.267 to 0.573 lb ai/A.

Exposure Profile Non

- occupational exposures to isofetamid are only expected for short

- term durations;

o ccupational e xposures a re expected for short

- and intermediate

- term durations. The dermal route of exposure is not as sessed because there is no dermal hazard identified

. The proposed residential u se on turf result s in inhalation exposures for adults (handlers) and post

- application incidental oral exposures for children (1 to <2 years old)

. Both proposed labels require the following personal protective equipment (PPE): long

- sleeved shirt and long pants, socks, shoes, and chemical resistant gloves made of any waterproof material.

Hazard Characterization In repeated dose studies, the liver w as the primary target organ in the rat, mouse

, and dog, as indicated by increased liver weights, changes in the clinical chemistry values, and liver hypertrophy. A second target organ was the thyroid in the rat and dog, as indicated by changes in thyroid weights and histopathology. Adrenal weight changes were observed in the subchronic mouse and dog studies. In the mouse, chronic no

- observed

- adverse

- effect levels ( NOAELs ) and lowest

- observed

- adverse

- effect

- levels ( LOAELs ) for liver toxicity were lower th an those for subchronic exposure. In the rat and dog, the dose levels where toxicity was observed were similar or higher in the chronic studies compared with the respective subchronic studies, showing an absence of progression of liver toxicity with time. There was no evidence of carcinogenicity in the rat or mouse cancer studies, further supporting the absence of progression of toxicity; the mutagenicity battery was negative. There are no genotoxicity, neurotoxicity, or immunotoxicity

concerns. Isofeta mid is classified as “ Not Likely to be Carcinogenic to Humans” based on the absence of increased tumor incidence in acceptable/guideline carcinogenicity studies in rats and mice. Isofetamid is not acutely toxic; it is classified as Toxicity Category III f or acute oral and dermal exposure, and Toxicity Category IV for inhalation exposure. Furthermore, it is not irritating to the eye or skin, and it is not a dermal sensitizer.

### Page 5 of 22

Developmental toxicity was not observed in the rat or rabbit. However, d ecreased offspring body weight and weight gain was observed in both sexes and generations in the multi

- generation reproduction study in the presence of parental toxicity. A de rmal point of departure (POD) i s not cho sen because systemic toxicity i s not see n in 28

- day dermal toxicity in rats at the limit dose (1

, 000 mg/kg/day). The short

- and intermediate

- term inhalation and incidental oral POD s are based on decreased pup body weight in both sexes and generations in a multi

- generation reproduction rat study with a NOAEL of 76.6 mg/kg/day.

Combining Exposures/Risk Estimates Since oral and inhalation endpoints are based on the same effect s , these routes of exposure may be combined for risk assessment. However, the dermal route of exposure cannot be aggregat ed with oral or inhalation routes because there is no dermal endpoint.

Summary of Residential Handler Non

- Cancer Exposure and Risk Estimates Residential h andler inhalation risk estimates for all scenarios are not of concern. Short

- term inhalation margins of exposure (MOEs) range from 850, 0 00 to 18 ,000,000.

Summary of Residential Post

- Application Non

- Cancer Exposure and Risk Estimates Although residential dermal exposure is expected following the treatment of turf , a quantitative post

- application dermal risk assessment was not conducted because a dermal hazard was not identified for isofetamid

. S hort

- term incidental oral post

- application risk estimates (which are protective of intermediate

- term risk estimates) for all scenarios are not of concern to HED ( MOEs range from 5 ,90 0 to 4 ,000,000)

. Intermediate

- term incidental oral post

- application exposures are possible (i.e. from soil ingestion due to the persistence of isofetamid ); however, the short

- term incidental oral exposures are protective of the possible intermediate

- term incidental oral exposures because the POD for both durations is the same. Post

- application inhalation exposure is expected to be negligible for the proposed residential uses.

Summary of Aggregate Aggregate risk estimates are n ot of concern. The most protective risk estimate for adult handler inhalation exposures is based on liquid application to lawns/turf with a hose

- end sprayer which results in an MOE of 850

, 0 00. The most protective risk estimate for children’s post

- applica tion incidental oral exposures is based on li quid application to residential lawns/turf which results in an MOE of 5 ,900

. Summary of Occupational Handler Non

- Cancer Exposure and Risk Estimates The results of the occupational handler exposure and risk asse ssment indicate that short

- and intermediate

- term inhalation risks are not of concern at baseline (i

. e. without PPE )

. S hort

- and intermediate

- term MOE s rang e from 24,000 to 8

, 5 00,0 00

. HED has no data to assess exposures to pilots using open cockpits ; only engineering control (enclosed cockpit) data are available to assess risks to handlers operating aircrafts.

### Page 6 of 22

Summary of Occupational Post

- Application Non

- Cancer Exposure and Risk Estimates An occupational post

- application dermal exposure and risk ass essment was not conducted because a dermal hazard was not identified for isofetamid

. Based on the Agency's current practices, a quantitative non

- cancer occupational post

- application inhalation exposure assessment was not performed for isofetamid 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 isofetamid

. Restricted Entry Interval The 12

- hour REI listed on the label s is adeq uate to protect agricultural workers from post

applicati on exposures to isofetamid

.

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. T hese data, which include PHED Version 1.1; the AHETF database; the ORETF database ; the Residential SOPs ( Lawns/Turf ), are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable ethics requir ements. 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 1



### .

2.0 Risk Assessment Conclusions and Recomme ndations

There are no occupational/residential risk estimates of concern associated with the proposed new uses of isofetamid

.

2.1 Summary of Risk Estimates

Residential Exposure and Risk Estimates The results of the residential handler exposure and risk assessment indicate that short

- term inhalation risks do not exceed HED’s level of concern ( LOC ) (i.e. an MOE < 100). Handler risk estimates for all scenarios are not of concern. Short

- term inhalati on MOEs range from 850,000
to 18 ,000,000. Although residential dermal exposure is expected following the treatment of turf, a quantitative post

- application dermal risk assessment was not conducted because a dermal hazard was not identified for isofetamid

. Short

- term incidental oral post

- application risk estimates for all scenarios are not of concern to HED ( MOEs range from 5 ,900 to 4,000,000) bec ause they do not exceed the LOC for incidental oral exposure (i.e. an MOE < 100)

. Intermediate

- term incidental oral post

- application exposures are possible (i.e. from soil ingestion due to the persistence of isofetamid ); however, the short

- term incidental oral exposures are protective of the possible intermediate

- term incidental oral exposures because the POD for both durations is the same. Post

- application inhalation exposure is expected to be negligible for the proposed residential uses.

1 http://www.epa.gov/pesticides/science/handler

- exposure

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

- app

- exposure

- data.html

### Page 7 of 22

Occupational Exposure and Risk Estimates The results of the occupational handler exposure and risk assessment indicate that short

- and intermediate

- term inhalation risks do not exceed HED’s level of concern (i.e. the LOC i s an MOE < 100 for short

- and intermediate

- term exposures) at baseline miti gation (no PPE). Since the short

- and intermediate

- term PODs are the same, the inhalation MOE s are also the same, ranging from 24,0 00 to 8,5 00 ,000

. Dermal handler and post

- application exposure and risk
assessment s w ere not conducted because a dermal haza rd was not identified for isofetamid

.

2.2 Label Recommendations

There are no label recommendations based on the residential or occupational assessment s

.

2.3 Data Deficiencies and Requirements

There are no data deficiencies or data requirements for the new active ingredient, isofetamid

.

3 .0 Hazard Characterization

In repeated dose studies, the liver was the primary target organ in the rat, mouse and dog, as indicated by increased liver weights , changes in the clinical chemistry values, and liver hypertrophy. A second target organ was the thyroid in the rat and dog, as indicated by changes in thyroid weights and histopathology. Adrenal weight changes were observed in the subchronic mouse and do g studies. In the mouse, chronic NOAELs and LOAELs for liver toxicity were lower than those for subchronic exposure. In the rat and dog, the dose levels where toxicity was observed were similar or higher in the chronic studies compared with the respectiv e subchronic studies, showing an absence of progression of liver toxicity with time. There was no evidence of carcinogenicity in the rat or mouse cancer studies, further supporting the absence of progression of toxicity; the mutagenicity battery was negati ve.

Developmental toxicity was not seen in the rat or rabbit. Decreased offspring body weight and weight gain was observed in both sexes and generations in the multi

- generation reproduction study in the presence of parental toxicity. The immunotoxicity study in the mouse was negative. No neurotoxic effects were observed in the neurotoxicity battery.

In acute studies, isofetamid is in Toxicity Category III for the LD 50 

### studies following oral, dermal exposure, and Toxicity Category IV following inhalat ion exposure; it is not irritating to the eye or skin (Toxicity Category IV) and is not a dermal sensitizer.

Dermal endpoints ( for either the short

- or intermediate

- term exposure durations ) were not selected because 1) there were no systemic effects noted in a dermal subchronic study up to the limit dose of 1000 mg/kg/day; 2) there are no concerns by the dermal route for the effects seen in the oral acute neurotoxicity study at 2000 mg/kg, or the multi

- generation reproduction study at 679 mg/kg/day, b ecause the dermal absorption factor is low (8%) and dermal dose levels required to produce these effects would have to significantly exceed the dermal limit dose; and 3) there are no immunotoxicity concerns. There are no long

- term dermal scenarios anticip ated for this risk assessment.

### Page 8 of 22

For the incidental oral endpoints (both short

- and intermediate

- term), the multi

- generation reproduction study was chosen because the exposure is appropriate for the population (infants and children), duration (1

- 30 days a nd 1

- 6 months) and exposure scenario (hand

- to

- mouth activity) of concern. The NOAEL is 76.6 mg/kg/day and the LOAEL is 679 mg/kg/d based on decreased pup body weight in both sexes and generations.

An inhalation study is not included in the available database so inhalation endpoints for occupational and residential exposures were derived from oral studies. The inhalation study was waived based on a weight of evidence decision (HASPOC memo, J. Leshin, TXR0057008 ). For short

- and intermediate inhalat ion scenarios, the NOAEL of 7 6.6 mg/kg/day was used as the POD from a multi

- generation reproduction rat study, with the LOAEL of 679/775 mg/kg/day (males/females) based on decreased pup body weight in both sexes and generations

. This study was chosen becau se the duration is appropriate for short

- and long

- term exposure scenarios, and the POD is protective of all adverse effects seen in other toxicity studies in the database. There are no long

- term inhalation scenarios anticipated for this risk assessment.

Acute Toxicity

Table 3.1. Summary of Acute Toxicity Data for Isofetamid (Technical Active Ingredient )

Guideline No. Type of study MRID Results Toxicity Category

870.1100 Acute oral (rat) 49032504 LD 50 > 2000 mg/kg III

870.1200 Acute dermal (rat) 49032505 LD 50 > 2000 mg/kg III

870.1300 Acute inhalation (rat) 49032506 LC 50 > 4.28 mg/L IV

870.2400 Acute eye irritation (rabbit) 49032507 Non

- irritating IV

870.2500 Acute dermal irritation (rabbit) 49032508 Non

- irritating IV

870.2600 Skin sensitization (mouse) 49032509 Not a dermal sensitizer N/A



### Toxicological PODs Used for Risk Assessment
Table 3.2. Summary of Toxicological Doses and Endpoints for Is ofetamid for Use in Dietary, Non

Occupational , andOccupational Human Health Risk Assessments

Exposure/ Scenario Point of

Departure Uncertainty/FQPA

Safety Factors RfD, PAD,

Level of Concern for Risk Assessment Study and Toxicological Effects

Incidental Oral Short

Term (1

- 30 days) and Intermediate

Term (1

- 6 months) NOAEL = 76.6

mg/kg/day UF A = 10x

UF H = 10x FQPA SF= 1x Residential

LOC for MOE = 100 Reproduction and fertility effects (rat)

LOAEL = 679/775 mg/kg/d based on decreased pup body weight in both sexes and generations and slightly delayed sexual maturation in F 1 females.

### Page 9 of 22

Table 3.2. Summary of Toxicological Doses and Endpoints for Is ofetamid for Use in Dietary, Non

Occupational , andOccupational Human Health Risk Assessments

Exposure/ Scenario Point of

Departure Uncertainty/FQPA

Safety Factors RfD, PAD,

Level of Concern for Risk Assessment Study and Toxicological Effects

Dermal Short

- Term (1

- 30 days) and Intermediate

Term (1

- 6 months) No systemic toxicity was seen up to the limit dose in a 28

- day rat dermal toxicity study up to the

limit dose

. No developmental effects seen in the developmental toxicity studies in rat and rabbit. Therefore, a dose and endpoint were not identified for this risk assessment

.

Inhalation Short

- Term (1

- 30 days) and Intermediate

Term (1

- 6 months) NOAEL = 76.6

mg/kg/day UF A = 10x

UF H = 10x FQPA SF= 1x Residential

LOC for MOE = 100

Occupational LOC for MOE = 100 Reproduction and fertility effects (rat)

LOAEL = 679/775 mg/kg/d based on decreased pup body weight in both sexes and generations and slightly delayed s exual maturation in F 1 females.

Cancer (oral, dermal, inhalation) Classification: A cancer classification has not yet been assigned to isofetamid. However, neither

the rat chronic/oncogenicity nor the mouse carcinogenicity study produced tumors at levels up to the limit dose (rat) or half the limit dose (mouse). Point of Departure (POD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF L = use of a LOAEL to extrapolate a NOAEL. UF S = use of a short

- term study for long

- term risk assessment. FQPA SF = FQPA Safety Factor. MOE = margin of exposure. LOC = level of c oncern. N/A = not applicable.


### Absorption A dermal absorption factor i s not used in this assessment because a dermal toxicity POD i s not identified based on a 28

- day dermal toxicity study in rats

. Since the short

- and intermediate

- term inhalation PODs a re not based on a route

- specific toxicity stud y , inhalation absorption is assumed to be equivalent to the oral

. Body Weight The standard female body weight ( 69 kg) i s used for all adult exposure scenarios covered in this risk assessment since the endpoint s selected a re based on developmental and fetal effects. The standard body weight for children 1 to <2 years old is 11 kg.

### Page 10 of 22

4 .0 Use Profile

Table 4.1

. Summary of Proposed Directions for Use of Isofetamid a

Application Timing, Type, and Equipment Formulation

[EPA Reg. No.] Trade Name b Maximum

Application Rate Max. No.

of Apps per Season Max.

Seasonal Application Rate RTI c
Use Directions and Limitations

days

Almond

Foliar (ground, aerial, chemigation) 36 .0% SC

[71512

- EE ] Isofetamid 400SC Agricultural Fungicide

3.33 lb ai/gal 17 fl oz/A

0.442 lb ai/A

0.0442 lb ai/gal 4 68 fl oz/A 7

- 14 Spray volume will usually range from 20 to 100 gallons per acre for dilute sprays, and 5 to 10 gallons per acre for concentrate ground and aerial
sprays. Do not make more than 2 sequential applications of Isofetamid 400SC before rotating to a fungicide with a different mode of action. Do not apply after first cover.

Lettuce (Head and Leaf)

Foliar (ground, aerial, chemigation) 36.0% SC

[71512

- EE ] Isofetamid 400SC Agricultural Fungicide

3.33 lb ai/gal 1 2.3 fl oz/A

0. 320 lb ai/A

0.0320 lb ai/gal 2 24.6 fl oz/A 14 Spray volume will usually range from 20 to 100

gallons per acre for dilute sprays, and 5 to 10 gallons per acre for concentrate ground and aerial sprays. Do not make more than 2 sequential applications of Isofetamid 400SC before rotating to a fungicide with a different mode of action. The PHI is 14 days.

Grapes, Crop Subgroup 13

- 07F (including Amur river grape; gooseberry; grape; kiwifruit, hardy; maypop; schisandra berry; and cultivars, varieties and/or h ybrids of these)

Foliar (ground, aerial, chemigation) 36.0% SC

[71512

- EE ] Isofetamid 400SC Agricultural Fungicide

3.33 lb ai/gal 22 fl oz/A

0. 572 lb ai/A

lb ai/gal 3 6 6 fl oz/A 7

- 14 Spray volume will usually range from 20 to 100 gallons per acre for dilute sprays, and 5 to 10 gallons per acre for concentrate ground and aerial sprays. Do not make more than 2 sequential applications of Isofetamid 400SC before rotating to a fungicide wi th a different mode of action. The PHI is 14 days.

Low Growing Berry, Crop Subgroup 13

- 07G (includes bearberry; bilberry; blueberry, lowbush; cloudberry; cranberry; lingonberry; muntries; partridgeberry; strawberry; and cultivars, varieties, and/or hybrids of these)

Foliar (ground, aerial, chemigation) 36.0% SC

[71512

- EE ] Isofetamid 400SC Agricultural Fungicide

3.33 lb ai/gal 17 fl oz/A

0.442 lb ai/A

0.0442 lb ai/gal 5 87.5 fl oz/A 7

- 14 Spray volume will usually range from 20 to 100

gallons per acre for dilute sprays, and 5 to 10 gallons per acre for concentrate ground and aerial sprays. Do not make more than 2 sequential applications of Isofetamid 400SC before rotating to a fungicide wi th a different mode of action. The PHI is 0 days

.
Rapeseed (Canola), Crop Subgroup 20A (includes borage; carambe; cuphea; echium; flax seed; gold of pleasure; hare’s ear mustard; lesquerella; lunaria; meadowfarm; milkweed; mustard seed; oil radish; poppy seed; rapeseed ( Brassica napus
, B. campestris , and Crambe abyssinica (oilseed

- producing varieties only

which include canola and crambe)); sesame; sweet rocket; and cultivars varieties, and/or hybrids of these)

Foliar (ground, aerial, chemigation) 36.0% SC

[71512

- EE ] Isofetamid 400SC Agricultural Fungicide

3.33 lb ai/gal 1 2 fl oz/A

0. 312 lb ai/A 2 24 fl oz/A 14 Spray volume will usually range from 20 to 100 gallons per acre for dilute sprays, and 5 to 10 gallons per acre for concentrate ground and aerial sprays. Do not make more than 2 sequential applications of Isofetamid 400SC before rotating to a fungicide w ith a different mode of action.

### Page 11 of 22

Table 4.1

. Summary of Proposed Directions for Use of Isofetamid a

Application Timing, Type, and Equipment Formulation

[EPA Reg. No.] Trade Name b Maximum

Application Rate Max. No.

of Apps per Season Max.

Seasonal Application Rate RTI c
Use Directions and Limitations

days

Turfgrass (including golf courses, sod farms, seed farms, college and professional sports fields, residential and commercial lawns )

Foliar (ground only) 36.0 % SC

[ 71512

- EG ] Isofetamid Turf Fungicide

3.33 lb ai/gal 21.8 fl oz/A

0.5 fl oz /1000 sq ft

0.567 lb ai/A

0.0000130 lb ai/1000 sq ft

0.00650 lb ai/gal 8 140 fl oz/A

3.2 fl oz /1000 sq ft 14 Isofetamid may be applied with all types of spray

equipment normally used for ground applications on turfgrasses. Do not apply isofetamid through any type of irrigation system. Do not apply isofetamid by aerial application. Do not apply more than two consecutive applications of isofetamid. Subsequent applications should be alternated with another registered fungici de with a different mode of action.

a RTI = re

- treatment interval. PHI = pre

- harvest interval. b Formulation code: SC = suspension concentrate.

c Based on the label for Reg. No. 71512

- EG, the most concentrated dilution spray volume is 25 fl oz of Isofetamid Turf Fungicide per 100 gallons of spray solution.



### 5 .0 Residential Exposure and Risk Estimates

At this time, t here are newly propose d residential uses of isofetamid that may lead to handler and post

- application exposures for both adults and children

. Adults may be exposed during handling and post

- application activities (via dermal and inhalation routes; children may be exposed during post

- application activities (via dermal and incidental oral routes). However, since a d ermal hazard has not been identified for isofetamid , t he only exposure scenarios quantitatively assessed are handler inhalation for adults, and post

- application incidental oral for children. These uses have been assessed with current policies which includ e updates to HED’s 2012 Residential SOPs 2 

### along with policy change s for body weight assumptions.

The only EP that may lead to residential exposures (handler and post

- application exposure) is EPA Reg. No. 71512

- EG (foliar and systemic insect control in tur fgrass including golf courses, residential lawns, and recreational turfgrass).

5 .1 Residential Handler Exposure/Risk Estimates

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 exposures can vary depending on the specifics of each task. Residential handlers are addressed somewhat differently by HED as homeowners are assumed to complete all elements of an application without use of any protective equipment.

2 Available: http://www.e pa.gov/pesticides/science/residential

- exposure

- sop.html

### Page 12 of 22

Since the proposed turf label (EPA Reg. No. 71512

- EG) include s residential use sites, prohibition of use by homeowners is not enforceable, and use by homeowners is possible. Thus, residential handler exposure an d risk estimates have been calculated for all possible residenti al exposure scenarios. However, s ince there are no toxicity findings for the short

- term dermal route of exposure up to the limit dose, the residential handler assessment only includes the inh alation route of exposure.

Residential Handler Exposure Data and Assumptions A series of assumptions and exposure factors served as the basis for completing the residential handler risk assessments. Each assumption and factor is detailed below.

Application Rate : Refer to the proposed use pattern table in Section 4.0.

Unit Exposures and Area Treated or Amount Handled : Unit exposure values and estimates for area treated or amount handled were taken from HED’s 2012 Residential SOPs 3 

### ( Lawns/Turf )

.
Exposure Duration: Residential handler exposure is expected to be short

- term in duration. Intermediate

- term exposures are not likely because of the intermittent nature of applications by homeowners

.

Residential Handler Non

- Cancer Exposure and Risk Es timate Equations The algorithms used to estimate exposure and dose for residential handlers can be found in the 2012 Residential SOPs 4 

### ( Lawns/Turf )

. Combining Exposures/Risk Estimate s: The dermal route of exposure does not need to be combined with another route of exposure or included in the aggregate risk assessment because there is no identified dermal hazard

. Summary of Residential Handler Non

- Cancer Exposure and Risk Estimates Handler risk estimates were assessed for all possible residential handler scenarios in which homeowners may be exposed to is o fetamid . Risk estimates of all possible scenarios are not of concern. Short

- term inhalation MOEs range from 850,000 to 18,000,000 as summarized in Table 5.1.

Table 5.1

. Residentia l Handler Non

- C ancer Exposure and Risk Estimates for Isofetamid

Application Equipment Crop or Target Inhalation Unit Exposure Maximum

Application Rate a Amount Handled Daily b Inhalation

Dose c MOE d mg/lb ai mg/kg/day
Mixer/Loader/Applicator for Liquid Formulations Manually

Pressurized H andwand Outdoor Broadcast: Lawns/Turf 0.018 0.00650 lb ai/gal 5

gal 0.00000 850 9

, 0 00,000

3 Available: http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html

4 Available: http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html

### Page 13 of 22

Table 5.1

. Residentia l Handler Non

- C ancer Exposure and Risk Estimates for Isofetamid

Application Equipment Crop or Target Inhalation Unit Exposure Maximum

Application Rate a Amount Handled Daily b Inhalation

Dose c MOE d mg/lb ai mg/kg/day

Hose

- End S prayer Outdoor Broadcast: Lawns/Turf 0.022 0.567 lb ai/A 0.5

acres 0.0000 900 85 0,000

Backpack Outdoor Broadcast: Lawns/Turf 0.14 0.00 650 lb ai/gal 5

gal 0.0000 660 1, 200,000

Sprinkler C an Outdoor Broadcast: Lawns/Turf 0.022 0 .0000130 lb ai/sq ft 1000

sq ft 0.00000 410 18,0 00,000

a Based on maximum application rate s on proposed label

, EPA Reg. No. 71512

- EG, for liquid applications to turf. b Based on HED’s 2012 Residential SOPs: Lawns/Turf ( http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html ).

c Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or lb ai/ gal) × Amount Handled ( A/day or gallons/day) ÷ BW ( 69 kg adult ). d Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). Short

- Term Inhalat ion NOAEL = 76.6 mg/kg/day

. Level of concern = 10 0.



### 5

. 2 Residential Post

- A pplication Exposure/Risk Estimates

There is the potential for post

- application exposure for individuals as a result of being in an environment that h as been previously treated with isofetamid

. E PA Reg. No. 71512

- EG may lead to residential post

- applications exposures because it is proposed for use on turf areas associated with gol f courses (greens, tees, and fairways), college and professional sports f ields, and residential lawns. Since dermal hazard has not been identified for isofetamid , a quantitative assessment for dermal exposure is not necessary and the only post

- application exposure scenarios quantitatively assessed are for children 1 to <2 year s old who may exp erience short

term incidental oral exposure to isofetamid from treated turf. Intermediate

- term incidental oral post

- application exposures are possible (i.e. from soil ingestion due to the persistence of isofetamid ); however, the short

- ter m incidental oral exposures are protective of the possible intermediate

- term incidental oral exposures because the POD for both durations is the same. Post

- application inhalation exposure is expected to be negligible for the proposed residential

uses.

The lifestage (children 1 to <2 years old) selected for each post

- application scenario is based on an analysis provided as an Appendix in the 2012 Residential SOPs 5 

### . This lifestag e is not the only lifestage that could be potentially exposed for these post

- application scenarios; however, the assessment of these lifestages is health protective for the exposures and risk estimates for any other potentially exposed lifestages.

Residential Post

- App lication Exposure Data and Assumptions 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 6 

### (Lawns/Turf)

.

5 Available: http://www.epa.gov/pesticides /science/residential

- exposure

- sop.html

6 Available: http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html

### Page 14 of 22

In accordance with 40CFR158, turf transferrable residue (TTR) dat a are required for all occupational (e.g. sod farms, golf courses, parks, and recreational areas) or residential turf uses that could result in post

- application exp osure to turf. Thus, i n addition to the SOPs, the registrant has submitted chemical

- specifi c TTR data ( DP 411110, DP411111, DP411112 , N. Keller, 10 / 30 /20 13 ). The high

- end TTR value chosen to be protective of all exposure scenarios (regardless of formulation applied), is the predicted Day 0 residue from the Pennsylvania site of 0.0761 μg/cm 2 

### . Th is value is based on a target application rate of 0.454 lb ai/A, and must be adjusted for the proposed application rates in quantitative post

- application risk estimate calculations. Table 5.2.1 provides a regression summary for the predicted Day 0 TTR val ue associated with each TTR study.

Table 5.2.1 . Regression S ummary for Turf Treated with Three Applications of Isofetamid a

Statistic IKF

- 5411 400SC Formulation Arkansas Pennsylvania North Carolina

Actual Average Measured Residue

on Day 0 (μg/cm 2 ) 0. 226 (first application)

0.0244 (second application)

0.1537 (third application) 0.0638 (first application)

0.0521 (second application)

0.0758 (third application) 0.0179 (first application)

0.0199 (second application)

0.0147 (third application)
Actual Average on Day 0 After Third Application (μg/cm 2 ) 0.1537 0.0758 0.0147

Predicted Day 0 Residue (μg/cm 2 ) 0.0313 0.0761 b 0.0135
Slope

- 0.3348

- 0.3321

- 0.3214 Half

- life (days) 2. 07 2.09 2.16

R 2 0.891 0.9923 0.9624

a Regression data is based on TTRs collected after the third (last) application. All applications were made at a target rate of 0.454 lb ai/A. Actual application rates range from 0.454 to 0.471 lb ai/A). b The TTR value recommended for turf post

- application risk assessment, regardless of formulation applied: TTR for of 0.567 lb ai/A = 0.0761 μg/cm 2 × (0.567 lb ai/A ÷ 0.454 lb ai/A) = 0.0950 μg/cm 2

.



### Residential Post

- App lication Non

- Cancer Exposure and Risk Equations The algorithms used to estimate residential post

- application exposure and dose can be found in th e 2012 Residential SOPs 7 

### (Lawns/Turf)

. Combining Exposure and Risk Estimates The dermal route of exposure does not need to be combined with the assessed incidental oral
route of exposure or included in the aggregate risk assessment because there is no identified dermal hazard

.

7 Available: http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html

### Page 15 of 22

Summary of Residential Post

- App lication Non

- Cancer Exposure and Risk Estimates Table 5.2 .2 presents the post

- application incidental oral MOE values calculated based on the scenario of liquid application of isofetamid to turf

. Post

- application risk estimates for all incidental oral scenarios are not of concern (MOEs range from 5 ,900 to 4 ,000,000). T he 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. However, combining these scenarios would be overly

- conservative because of the conservative nature of each individual assessment. Therefore , the hand

- to

- mouth post

- application exposure scenario for children 1 < 2 years old should be considered a protective estimate of children’s exposure to pesticides used indoors. Furthermore, incidental oral risk estimates are highly conservative because t he short

- and intermediate

- term incidental oral POD is based on a 90

- day exposure duration.

Table 5.2. 2

. Residential Post

- Application Non

- Cancer Exposure and Risk Estimates for Isofetamid

Lifestage Post

- Application Exposure Scenario Application Rate a Dose b MOEs c Use Site Route of Exposure mg/kg/day

Children 1 to <2 years old Liquid Application
to Turf Hand to Mouth 0. 567 lb ai/A 0.0 130 5 ,900 Object to Mouth 0.000 395 1 90 ,000 Incidental Soil Ingestion 0.0000 192 4,000 ,000

a Based on proposed label: EPA Reg. No. 71512

- EG for liquid applications to turf. b Dose (mg/kg/day) equations: Hand

- to

- Mouth Dose = hand residue loading ( μ g/cm 2 ) × fraction of hand mouthed (0.127) × surface area of 1 hand (150 cm 2 ) × exposure time (1.5 hrs /day) × # of replenishment intervals/hr (4 int/hr) × (1

- ((1

- saliva extraction factor (0.5))^(Number of hand

- to

- mouth events per hour (13.9 events/hr) ÷ # of replenishment intervals/hr)) ÷ body weight (11 kg). Object

- to

- Mouth Dose = object residue loading ( μ g/cm 2 ) × unit conversion factor (0.001 mg/ μ g) × object surface area mouthed / event (10 cm 2 /event) × exposure time (1.5 hrs/day) × # replenishment intervals/hr (4 int/hr) × (1

- ((1

- saliva extraction factor (0.50))^(# Object

- to

- Mouth Events/hr (8.8 events /hr) ÷ # replenishment intervals/hr)) ÷ body weight (11 kg). Soil Ingestion = soil residue (μg/g) × ingestion rate (50 mg/day) × conversion factor (0.000001 g/μg) ÷ body weight (11 kg). TTR for liquid application rate of 0. 567 lb ai/A calculated based on chemical

- specific study = 0.0 95 0 μg/cm 2

. c MOE = NOAEL ÷ Daily Dose (mg/kg/day). ST/IT Incidental Oral NOAEL = 76.6 mg/kg/day. Level of concern = 100.



### 5. 3 Residential Risk Estimates for Use in Aggregate Assessment

For the purpose of the isofetamid aggregate human health risk assessment, a summary of the most protective residential exposure estimates for all proposed residential uses are provided in Table 5.3

. Based on the residential use profile

, and the 2012 Revised Residential SOPs, only short

- term inhalation residential handler exposures (for adults) and short

- /intermediate

- term incidental oral post

- application exposures (for children) should be included in the aggregate risk
assessment. It is noted that intermediate

- term incidental oral post

- application exp osures are possible (i.e. from soil ingestion due to the persistence of isofetamid ) ; however, the short

- term incidental oral exposures are protective of the possible intermediate

- term incide ntal oral exposures because the POD for both durations is the same.

T he recommended exposure contribution for aggregate risk assessment is based on the most protective risk estimate from liquid application to turf (MOE = 850,000 for adults and MOE = 8.90 0 for children)

.

### Page 16 of 22

Table 5.3

. Scenarios Recommended for Aggregate Risk Assessment of Isofetamid

Scenario Daily Dose a MOE b mg/kg/day Adults Residential Handler Inhalation Exposure (Applying Liquids to Lawns/Turf with a Hose

- End Sprayer) 0.000 0900 850 ,0 00

Children (1 to <2 Years Old)
Post

- Application Incidental Oral Exposure : Hand

- to

- Mouth (After Liquid Application to Lawns/Turf ) 0.0 130 5 ,900

a D aily Dose = See Table 5 .1 for a dult h andler s cenarios and Table 5 .2 .2 for post

- application incidental oral scenarios. Adults and c hildren based on EPA Reg. No. 71512

- EG (SC). b MOE = NOAEL/ Daily Dose (mg/kg/day)

. ST /IT Incidental Oral = 76.6 mg/kg/day. ST Incidental Oral LOC = 100.



### 5

. 4 Spray Drift

Spray drift is a potential source of exposure to those nearby pesticide applications. This is particularly the case with aerial application, but, to a lesser extent, spray drift can also be a potential source of exposure from the ground application method s (e.g. groundboom and airblast) employed for isofetami d. The agency has been working with the Spray Drift Task Force (a task force composed of various registrants which was developed as a result of a Data Call

- In issued by EPA), EPA Regional Offices

, and State Lead Agencies for pesticide regulation

, and othe r parties to develop the best spray drift management practices (see the agency’s Spray Drift website for more information). 8 

### The agency has also developed a policy on how to appropriately consider spray drift as a potential source of exposure in risk ass essm ents for pesticides.

The potential for spray drift will be quantitatively evaluated for each pesticide during the Registration Review process which ensures that all uses for that pesticide will be considered concurrently. The approach is outlined in the revised (2012) Standard Operating Procedures For Residential Risk Assessment (SOPs)

- Residential Exposure Assessment Standard Operating Procedures Addenda 1: Consideration of Spray Drift. This document outlines the quantification of indirect non

- occ upa tional exposure to drift.

5

. 5 Residential Bystander Post

- Application Inhalation Exposure

Volatilization of pesticides may be a source of post

- application inhalation exposure to individuals nearby pesticide applications. The agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipo ly/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).

8 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm

### Page 17 of 22

Du ring Registration Review, the agency will utilize this analysis to determine if data (i.e. flux studies, route

- specific inhalation toxicological studies) or fu rther analysis is required for isofetamid

.

6 .0 Occupational Exposure and Risk Estimates

6 .1 Agr icultural Occupational Handler Exposure/Risk Estimates

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.

Based on the anticipated use patterns and current labeling, types of equipment and techniques that can potentially be used, occupational handler exposure is expected from the proposed agricultural u ses. The quantitative exposure/risk assessment developed for occupational handlers is ba sed on several scenarios which include mixing/loading/applying an SC formulation of isofetamid . The use sites are summarized in Section 4.0 . Methods of application include aerial, airblast, chemigation, groundboom, and handhel d equipment. Refer to Table 6 .1 for a detailed list of each scenario.

Occupational Handler Exposure Data and Assumptions A series of assumptions and exposure factors served as the basis for co mpleting the occupational handler risk assessments. Each assumption and factor is detailed below on an individual basis.

Application Rate : Refer to the proposed use patter n table in Section 4.0

.
Unit Exposures: 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 AHETF database, the Outdoor Residential Exposure Task Force (ORETF) database, or other regis trant

- submitted occupational exposure studies. Some of these data are proprietary (e.g., AHETF data), and subject to the data protection provisions of FIFRA. The standard values recommended for use in predicting handler exposure that are used in this

ass essment, known as “unit exposures”, are outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table 9 

### ”, which, along with additional information on HED policy on use of surrogate data, including descriptions of the various source s, can be found at the Agency website 10



### .
Area Treated or Amount Handled : The area treated or amount handled is b ased on HED Exp oSAC Policy No. 9.1. Refer to Table 6 .1 for these assumptions for each scenario.

9 Available: http://www.epa.gov/opp00001/science/handler

- exposure

- table.pdf

10 Available: http://www.epa.gov/pesticides/science/handler

- exposure

- data.html

### Page 18 of 22

Exposure Duration: HED classifies exposures from 1 to 30 days as short

- term and exposures 30 days to six months as intermediate

- term. Exposure duration is determined by many things, including the exposed population, the use site, the pest pressure triggering the use of the pesticide, and the cultur al practices surrounding that use site. For most agricultural uses, it is reasonable to believe that occupational handlers will not apply the same chemical every day for more than a one

- month time frame; however, there may be a large agribusiness and/or

c ommercial applicators who may apply a produ ct over a period of weeks (e.g. completing multiple applications for mult iple clients within a region). Short

- term exposures are protective of the possible intermediate

- term exposures because the POD for both dur ations is the same.

Mitigation/Personal Protective Equipment: Results are presented for “baseline,” defined as a single layer of clothing consisting of a long sleeved shirt, long pants, shoes plus socks, no protec tive gloves, and no respirator.

Occupati onal Handler Non

- Cancer Exposure and Risk Estimate Equations The algorithms used to estimate non

- cancer exposure and dose for occupational handlers can be found in Appendix A

. Combining Exposures/ Risk Estimates The dermal route of exposure does not need t o be combined with the assessed inhalation route of
exposure or included in the aggregate risk assessment because there is no identified dermal hazard

. Summary of Occupational Handler Non

- Cancer Exposure and Risk Estimates The results of the occupational handler exposure and risk assessment indicate that short

- and intermediate

- term inhalation risks do not exceed HED’s LOC (i.e. MOE < 100 for short

- and intermediate

- term exposures ) at baseline mitigation (no PPE)

. Since the short

- and intermediate

term PODs are the same, the inhalation MOEs a re also the same, ranging from 24,0 00 to 8,5 00,000

. Note that o nly engineering control (enclosed cockpit) data are available to assess risks to handlers operating aircrafts.

The Agency matches quantitative occupational exposure assessment with appropriate characterization of exposure potential. While HED presents quantitative risk estimates for human flaggers whe n appropriate, agricultural aviation has changed dramatically over the pas t two decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of their membership, the use of GPS for swath guidance in agricultural aviation has grown steadily from the mid 1990’s. Over the same time period, the use of human flaggers for aerial pesticide applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent (2012) NAAA survey. The Agency will continue to monitor all available information sources to best assess and characterize the expos ure potential for human flaggers in agricultural aerial applications.

HED has no data to assess exposures to pilots using open cockpits. The only data available is for exposure to pilots in enclosed cockpits. Therefore, risks to pilots are assessed using the engineering control (enclosed cockpits) and baseline attire (long

- sleeve shirt, long pants, shoes, and socks); per the Agency’s Worker Protection Standard stipulations for engineering controls,

### Page 19 of 22

pilots are not required to wear protective gloves for the duration of the application . With this level of protection, there ar e no risk estimates of concern for applicators.

Table 6 .1. Occupational Handler Non

- Cancer E xposure and Risk Estimates for Isofetamid

.

Exposure Scenario Crop or Target a Baseline Inhalation Unit Exposure b Maximum

Application Rate c Area

Treated or Amount Handled Daily d Baseline Inhalation

Dose e MOE f

μg/lb ai lb ai/A Acres mg/kg/day ST/ IT LOC = 100

Mixer/Loader

Mixing/Loading Liquids for Aerial Application Orchard Crops

0.219 0.572 350 0.000 636 120 ,000
Sod Farms 0.567 350 0.000630 120 ,000 Typical Field Crops 0.442 350 0.000 491 160 ,000 High

- Acreage Field Crops 0. 312 1200 0.00119 64 ,000 Mixing/Loading Liquids for Airblast Application Orchard Crops 0.572 40 0.0000726 1,100,000

Mixing/Loading Liquids for Chemigation Orchard Crops 0.572 350 0.000636 120,000

Sod Farms 0.567 350 0.000630 120,000
Typical Field Crops 0.442 350 0.000491 160,000

High

- Acreage Field Crops 0.312 350 0.000346 220,000

Mixing/Loading Liquids for Groundboom Application Golf Courses

(tees and greens only) 0.567 5 0.00000900 8,500,000

Golf Courses (fairways, tees, and greens) 0.567 40 0.0000720 1,100,000

Sod Farms 0.567 80 0.000144 530,000
Typical Field Crops 0.442 80 0.000112 680,000
High

- Acreage Field Crops 0.312 200 0.000199 380,000

Applicator

Applying Sprays for Aerial Application Orchard Crops

0.0 049 0.572 350 0.0000142 5,400,000 Sod Farms 0.567 350 0.0000141 5,400,000 Typical Field Crops 0.442 350 0.0000110 7,000,000 High

- Acreage Field Crops 0.312 1200 0.0000267 2,900,000 Applying Sprays for Airblast Application Orchard Crops 4.71 0.572 40 0.00157 49,000

Applying Sprays for Groundboom Application Golf Courses

(tees and greens only)

0.34 0. 567 5 0.0000 140 5,5 00,000

Golf Courses (fairways, tees, and greens) 0.567 40 0.000112 68 0,000

Sod Farms 0. 567 80 0.000223 34 0,000 Typical Field Crops 0.442 80 0.000174 44 0,000 High

- Acreage Field Crops 0.312 200 0.000307 250 ,000 Flagger

Flagging for Aerial Applications Orchard Crops

0.35 0. 572 350 0.00102 75 ,000 Sod Farms 0.567 350 0.00101 76 ,000 Typical Field Crops 0.442 350 0.000786 97 ,000 High

- Acreage Field Crops 0.312 350 0.000554 140 ,000

### Page 20 of 22

Table 6 .1. Occupational Handler Non

- Cancer E xposure and Risk Estimates for Isofetamid

.

Exposure Scenario Crop or Target a Baseline Inhalation Unit Exposure b Maximum

Application Rate c Area

Treated or Amount Handled Daily d Baseline Inhalation

Dose e MOE f

μg/lb ai lb ai/A Acres mg/kg/day ST/ IT LOC = 100
Mixer/Loader/Applicator

M/L/A Liquids for Backpack Sprayers Landscaping (turf, lawns,

athletic fields, parks, etc) (Broadcast and Spot) 2.58 0. 000650 lb ai/gal 40

gallons 0.00000972 7,900,000

M/L/A Liquids for Manually

- Pressurized Handwand Sprayers Landscaping (turf, lawns,

athletic fields, parks, etc) 30 0. 000650 lb ai/gal 40

gallons 0.000113 680,000

M/L/A Liquids for Mechanically

Pressurized Handgun Sprayers Orchard Crops (Foliar) 3.9 0. 0572 lb ai/gal 1000

gallons 0.00323 24,000

Typical Field Crops (Foliar) 0. 0442 lb ai/gal 0.00249 31,000

Golf Courses (tees and greens only)

1.9 0.567 5

acres 0.0000781 980,000 Golf Courses (fairways, tees, and greens) Landscaping (turf, lawns, athletic fields, parks, etc)

a “Typical Field Cro ps” include lettuce (head and leaf ) and low growing berry crop subgroup 13

- 07G

. “Orchard Crops” include almonds and small fruit vine climbing crop subgroup 13

- 07F. “High

- Acreage Field Crops” includes rapeseed (canola)

. b Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” ( March 2012 ); Level of mitigatio n = Baseline.

c Based on the maximum application rates on the proposed label s (Reg. No s

. 71512

- EE and 71512

- EG ). d Exposure Science Advisory Council Policy #9.1.

e Inhalation Dose = Dermal Unit Exposure ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (A or gal/day) ÷ BW ( 69 kg). f Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). ST/IT NOAEL = 76.6 mg/kg/day. ST/IT LOC = 100.



### 6

. 2 Occupational Post

- App lication Exposure/ Risk Estimates

HED uses the term post

- application to describe exposures that occur when individuals are present in an environment that has been previously treated with a pesticide (also referred to as 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

- app lication exposure levels vary over time and depend o n such things as the type of activity, the nat ure 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

- applicat ion exposure.

Although isofetamid is persistent in soil, a n occupational post

- application dermal exposure and risk assessment was not conducted because a dermal hazard was not identified for isofetamid

. Occupational Post

- Application Inhalation Exposure/R isk Estimates There are multiple potential sources of post

- application inhalation exposure to individuals performing post

- application activities in previously treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides. The agency sought expert advice and input on issues related to volatilization of

### Page 21 of 22

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 Ana lysis ( 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 isofetamid

. In addition, the Agency is continuing to evalua te 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.

Although a quantitative occupational postapplication inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercial handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in higher exposure than postapplication exposure. Therefore, it is expected that these handler inhalation exposure estimates would be protective of most occupational postapplic ation inhalation exposure scenarios. Furthermore, i nhalation exposure during dusty mechanical activities such as shaking and mechanical harvesting is another potential source of post

application inhalation exposure. However, the airblast applicator scena rio is believed to represent a reasonable worst case surrogate estimate of post

- application inhalation exposure during these dusty mechanical harvesting activities. The non

- cancer inhalation risk estimate for commercial airblast application is not of conc ern (i.e. the MOE is greater than the LOC of 100 )

.

6. 3 Restricted Entry Interval

Isofetamid is classified as Toxicity Category III via the dermal route. It is not irritating to the eye or skin, nor a skin sensitizer. Typically, the REI specified on the proposed label is based on the acute toxicity of the active ingredient. Under 40 CFR 156.208 (c) (2) (iii), active ingredients classified as Acute III or IV for acute dermal, eye irritation

, and primary skin irrigation are assigned a minimum of 12 hour s for the REI . Thus, the 12

- hour REI on the proposed label s is acceptable for all proposed uses

.

### Page 22 of 22

Appendix A . Summary of Occupational Handler Non

- Cancer Algorithms

Average Daily Dose Potential daily exposures for occupational handlers are calculated using the following formulas: E=UE * AR * A * 0.001 mg/ug where: E = e xposure (mg ai/day), UE = u nit e xposure (μg ai/lb ai), AR = m aximum application rate according to proposed label (lb ai A or lb ai/gal), and A = a rea treated or amount handled (e.g., A/day, gal/day).

The daily doses are calculated using the following formula:

ADD= E * AF
BW where: ADD = average daily dose absorbed in a given scenario (mg ai/kg/day), E = e xposure (mg ai/day), AF = absorption fa ctor (dermal and/o r inhalation), and BW = body weight (kg).

Margin of Exposure Non

- cancer risk estimates for each application handler scenario are calculated using a Margin of Exposure (MOE), which is a ratio of the toxicological endpoint to the daily dose of concern. The daily dermal and inhalation dose received by occupational handlers a re compared to the appropriate POD ( i.e.

, NOAEL) to assess the risk to occupational handlers for each exposure
route. All MOE values a re calculated using the following formula:

MOE= POD
A DD where: MOE = margin of exposure: value used by HED to represent risk estimates (unitless), POD = point of departure (mg/kg/day), and ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).