Date: 

Subject: 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

July 25, 20 14 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

Isofetamid. Occupational and Residential Exposure and Risk Assessment for the 

Proposed New Uses of the New Active Fungicide, including Agricultural Uses on 

Almonds, Lettuce, Small Vine Climbing Fruits (Crop Subgroup 13-07F), Low 

Growing Berries (Crop Subgroup 13-07G), and Rapeseed (Crop Subgroup 20A); 

and Uses on Turf grass (including Golf Courses, Sod Farms, Seed Farms, 

Recreational Fields, and Commercial/Residential Lawns). 

PC Code: 270000 DP Barcode: 0 411113 

Decision No.: 474283 

Regulatory Action: Section 3 

Case No.: NA 

Petition No.: 3F8142 

Registration Nos.: 71512-ER, 715 12-EE, 71512-EG 

Risk Assessment Type: Occupationa l/Residential Exposure Assessment 

TXR No.: NA CAS No.: 8759 15-78-9 

MRID No.: NA 

From: 

Through: 

To: 

Introduction 

Nancy J. Keller, Chemist 

Risk Assessment Branch 3 

Health Effects Division (7509P) 

40 CFR: to be determined 

---

Barry 0' Keefe, Senior Biologist, ORE Team Leader /]( (J 'I/A A/) 

Risk Assessment Branch 3 (RAB3) r ~ 

Health Effects Division (7509P) ~ fi 

and 

Matthew Lloyd, Industrial Hygienist 

/l/

· 

, I ~ 

Alexandra LaMay, Biologist '{ : -cv v'(l'· )/ 

Exposure Science Advisory Committee (ExpoSAC) 

Health Effects Division (7509P) 

Heather Garvie/Tony Kish, RM #22 

Fungicide Branch (FB) 

Division (7505P) 

The Registration Division (RD) requested that the Health Effects Division (HED) conduct an 

occupational and residential exposure and risk assessment for all of the proposed new uses of the 

new active fungicide, isofetamid, including agricultural uses on almonds, lettuce, small vine 

climbing fruits (crop subgroup 13-07F), low growing berries (crop subgroup 13-07G), and 

Page 1 of22 
rapeseed (crop subgroup 20A); and uses on turf grass (including golf courses, sod farms, seed 

farms, recreational fields, and commercial/residential lawns). 

It is HED policy to use the best available data to assess exposure. Several sources of generic 

data were used in this assessment as surrogate data in the absence of chemical-specific data, 

including Pesticide Handlers Exposure Database Version 1.1 (PHED 1. 1); the Agricultural 

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

(ORETF) database; the Residential SOPs (Lawns/Turf). Some of these data are proprietary, and 

subj ect to the data protection provisions of the Federal Insecticide, Fungicide, and Rodenticide 

Act (FIFRA). 

Note: This memorandum was reviewed 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) currently 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 include agricultural food-uses 

and commercial/residential turf uses.

Isofetamid is a systemic, broad spectrum fungicide belonging to the thiophene 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 agricultural 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 (crop 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 

range from 0.267 to 0.573 lb ai/A.

Exposure Profile

Non-occupational exposures to isofetamid are only expected for short-term durations; 

occupational exposures are expected for short- and intermediate-term durations. The dermal 

route of exposure is not assessed because there is no dermal hazard identified. The proposed 

residential use on turf results 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 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 dog studies. In the mouse, chronic no-observed-adverse-effect levels (NOAELs) and 

lowest-observed-adverse-effect-levels (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 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. Isofetamid 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 for 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, 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. A dermal point of departure (POD) is not 

chosen because systemic toxicity is not seen 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 PODs 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 effects, these routes of exposure may 

be combined for risk assessment. However, the dermal route of exposure cannot be aggregated 

with oral or inhalation routes because there is no dermal endpoint.

Summary of Residential Handler Non-Cancer Exposure and Risk Estimates

Residential handler inhalation risk estimates for all scenarios are not of concern. Short-term 

inhalation margins of exposure (MOEs) range from 850,000 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. Short-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 5,900 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 not 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 850,000. The most protective risk estimate for children’s post-application 

incidental oral exposures is based on liquid 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 assessment indicate that short- and 

intermediate-term inhalation risks are not of concern at baseline (i.e. without PPE). Short- and 

intermediate-term MOEs range from 24,000 to 8,500,000. 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 assessment 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 labels is adequate to protect agricultural workers from postapplication 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. These 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 requirements. For certain studies, the ethics review may have 

included review by the Human Studies Review Board. Descriptions of data sources, as well as 

guidance on their use, can be found at the Agency website1. 

2.0 Risk Assessment Conclusions and Recommendations

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 inhalation 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) 

because 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 is an 

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 are also the same, 

ranging from 24,000 to 8,500,000. Dermal handler and post-application exposure and risk 

assessments were not conducted because a dermal hazard was not identified for isofetamid.

2.2 Label Recommendations 

There are no label recommendations based on the residential or occupational assessments.

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 dog 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 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. 

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 LD50 studies following oral, 

dermal exposure, and Toxicity Category IV following inhalation 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, because 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 anticipated 

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 and 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 inhalation scenarios, the NOAEL of 76.6 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 because 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 LD50 > 2000 mg/kg III

870.1200 Acute dermal (rat) 49032505 LD50 > 2000 mg/kg III

870.1300 Acute inhalation (rat) 49032506 LC50 > 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 Isofetamid for Use in Dietary, NonOccupational, 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 ShortTerm (1-30 

days) and 

IntermediateTerm (1-6 

months)

NOAEL = 76.6

mg/kg/day

UFA= 10x

UFH= 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 F1

females.
Page 9 of 22

Table 3.2. Summary of Toxicological Doses and Endpoints for Isofetamid for Use in Dietary, NonOccupational, 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 

IntermediateTerm (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 

IntermediateTerm (1-6 

months)

NOAEL = 76.6

mg/kg/day

UFA= 10x

UFH= 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 sexual maturation in F1

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. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in

sensitivity among members of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a 

NOAEL. UFS = use of a short-term study for long-term risk assessment. FQPA SF = FQPA Safety Factor. MOE 

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

Absorption

A dermal absorption factor is not used in this assessment because a dermal toxicity POD is not 

identified based on a 28-day dermal toxicity study in rats. Since the short- and intermediate-term 

inhalation PODs are not based on a route-specific toxicity study, inhalation absorption is 

assumed to be equivalent to the oral.

Body Weight

The standard female body weight (69 kg) is used for all adult exposure scenarios covered in this 

risk assessment since the endpoints selected are 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 Isofetamida

Application 

Timing, Type, 

and Equipment

Formulation

[EPA Reg. No.]

Trade Nameb

Maximum 

Application 

Rate

Max. No. 

of

Apps per

Season

Max. 

Seasonal 

Application 

Rate

RTIc

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

12.3 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 hybrids 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 66 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. 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 with 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

12 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 with a different mode of action.
Page 11 of 22

Table 4.1. Summary of Proposed Directions for Use of Isofetamida

Application 

Timing, Type, 

and Equipment

Formulation

[EPA Reg. No.]

Trade Nameb

Maximum 

Application 

Rate

Max. No. 

of

Apps per

Season

Max. 

Seasonal 

Application 

Rate

RTIc

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 fungicide 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, there are newly proposed 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 dermal 

hazard has not been identified for isofetamid, the 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 include updates to HED’s 2012 Residential 

SOPs2along with policy changes 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 turfgrass 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.epa.gov/pesticides/science/residential-exposure-sop.html
Page 12 of 22

Since the proposed turf label (EPA Reg. No. 71512-EG) includes residential use sites, 

prohibition of use by homeowners is not enforceable, and use by homeowners is possible. Thus, 

residential handler exposure and risk estimates have been calculated for all possible residential 

exposure scenarios. However, since 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 inhalation 

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 SOPs3(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 Estimate Equations

The algorithms used to estimate exposure and dose for residential handlers can be found in the 

2012 Residential SOPs4(Lawns/Turf).

Combining Exposures/Risk Estimates:

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 isofetamid. 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. Residential Handler Non-Cancer Exposure and Risk Estimates for Isofetamid

Application 

Equipment Crop or Target

Inhalation 

Unit 

Exposure

Maximum 

Application 

Ratea

Amount 

Handled 

Dailyb

Inhalation

Dosec

MOEd

mg/lb ai mg/kg/day

Mixer/Loader/Applicator for Liquid Formulations

ManuallyPressurized 

Handwand

Outdoor Broadcast: Lawns/Turf 0.018 0.00650

lb ai/gal

5

gal 0.00000850 9,000,000

 

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. Residential Handler Non-Cancer Exposure and Risk Estimates for Isofetamid

Application 

Equipment Crop or Target

Inhalation 

Unit 

Exposure

Maximum 

Application 

Ratea

Amount 

Handled 

Dailyb

Inhalation

Dosec

MOEd

mg/lb ai mg/kg/day

Hose-End 

Sprayer

Outdoor Broadcast: Lawns/Turf 0.022 0.567

lb ai/A

0.5

acres

0.0000900 850,000

Backpack Outdoor Broadcast: Lawns/Turf 0.14 0.00650

lb ai/gal

5

gal 0.0000660 1,200,000

Sprinkler Can Outdoor Broadcast: Lawns/Turf 0.022 0.0000130

lb ai/sq ft

1000

sq ft 0.00000410 18,000,000

a Based on maximum application rates 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 Inhalation NOAEL = 76.6 

mg/kg/day. Level of concern = 100.

5.2 Residential Post-Application Exposure/Risk Estimates

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

environment that has been previously treated with isofetamid. EPA Reg. No. 71512-EG may 

lead to residential post-applications exposures because it is proposed for use on turf areas 

associated with golf courses (greens, tees, and fairways), college and professional sports fields, 

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 years old who may experience shortterm 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-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.

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 SOPs5. This lifestage 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-Application 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 

SOPs6(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) data 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 exposure to turf. Thus, in addition to the SOPs, the 

registrant has submitted chemical-specific TTR data (DP411110, DP411111, DP411112, N. 

Keller, 10/30/2013). 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/cm2. This 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 value

associated with each TTR study.

Table 5.2.1. Regression Summary for Turf Treated with Three Applications of Isofetamida

Statistic

IKF-5411 400SC Formulation

Arkansas Pennsylvania North Carolina

Actual Average Measured Residue 

on Day 0

(μg/cm2)

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/cm2)

0.1537 0.0758 0.0147

Predicted Day 0 Residue

(μg/cm2)

0.0313 0.0761b 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/cm2 × (0.567 lb ai/A ÷ 0.454 lb ai/A) = 0.0950 μg/cm2.

Residential Post-Application Non-Cancer Exposure and Risk Equations

The algorithms used to estimate residential post-application exposure and dose can be found in 

the 2012 Residential SOPs7(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-Application 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). The 

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

Ratea

Doseb

MOEsc

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

0.0130 5,900

Object to Mouth 0.000395 190,000

Incidental Soil Ingestion 0.0000192 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 (μg/cm2) × fraction of hand mouthed (0.127) × surface area of 1 hand (150 cm2) 

× 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 (μg/cm2) × unit conversion factor (0.001 mg/μg) × object surface area mouthed 

/ event (10 cm2/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 = 0.0950 μg/cm2.

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 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.

The 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 = 

8.900 for children).
Page 16 of 22

Table 5.3. Scenarios Recommended for Aggregate Risk Assessment of Isofetamid

Scenario Daily DoseaMOEb

mg/kg/day

Adults 

Residential Handler Inhalation Exposure

(Applying Liquids to Lawns/Turf with a Hose-End Sprayer) 0.0000900 850,000

Children (1 to <2 Years Old)

Post-Application Incidental Oral Exposure: Hand-to-Mouth

(After Liquid Application to Lawns/Turf)

0.0130 5,900

a Daily Dose = See Table 5.1 for adult handler scenarios and Table 5.2.2 for post-application incidental oral

scenarios. Adults and children 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 methods (e.g. groundboom and airblast) 

employed for isofetamid. The agency has been working with the Spray Drift Task Force (a task 

force composed of various registrants which was developed as a result of a Data Call-In issued 

by EPA), EPA Regional Offices, and State Lead Agencies for pesticide regulation, and other 

parties to develop the best spray drift management practices (see the agency’s Spray Drift 

website for more information). 8 The agency has also developed a policy on how to 

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

pesticides. 

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

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

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

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

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

of indirect non-occupational exposure to drift.

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/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). 

 

8 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
Page 17 of 22

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.

6.0 Occupational Exposure and Risk Estimates

6.1 Agricultural 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 uses. The quantitative exposure/risk assessment developed for occupational handlers 

is based 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 handheld 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 completing the occupational 

handler risk assessments. Each assumption and factor is detailed below on an individual basis.

Application Rate: Refer to the proposed use pattern 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 registrant-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 

assessment, known as “unit exposures”, are outlined in the “Occupational Pesticide Handler Unit 

Exposure Surrogate Reference Table9”, which, along with additional information on HED policy 

on use of surrogate data, including descriptions of the various sources, can be found at the 

Agency website10.

Area Treated or Amount Handled: The area treated or amount handled is based on HED 

ExpoSAC 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 cultural 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 

commercial applicators who may apply a product over a period of weeks (e.g. completing 

multiple applications for multiple clients within a region). Short-term exposures are protective 

of the possible intermediate-term exposures because the POD for both durations 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 

protective gloves, and no respirator.

Occupational 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 to 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 intermediateterm PODs are the same, the inhalation MOEs are also the same, ranging from 24,000 to 

8,500,000. Note that only 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 when appropriate, agricultural aviation has changed dramatically over the past 

two decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of 

their membership, the use of GPS for swath guidance in agricultural aviation has grown steadily 

from the mid 1990’s. Over the same time period, the use of human flaggers for aerial pesticide 

applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent 

(2012) NAAA survey. The Agency will continue to monitor all available information sources to 

best assess and characterize the exposure potential for human flaggers in agricultural aerial 

applications.

HED has no data to assess exposures to pilots using open cockpits. The only data available is for 

exposure to pilots in enclosed cockpits. Therefore, risks to pilots are assessed using the 

engineering control (enclosed cockpits) and baseline attire (long-sleeve shirt, long pants, shoes, 

and socks); per the Agency’s Worker Protection Standard stipulations for engineering controls, 
Page 19 of 22

pilots are not required to wear protective gloves for the duration of the application. With this 

level of protection, there are no risk estimates of concern for applicators.

Table 6.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Isofetamid.

Exposure Scenario Crop or Targeta

Baseline 

Inhalation 

Unit 

Exposureb

Maximum

Application 

Ratec

Area 

Treated or 

Amount 

Handled 

Dailyd

Baseline Inhalation

Dosee MOEf

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 0.000636 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 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

0.0049

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 0.0000140 5,500,000

Golf Courses

(fairways, tees, and greens) 0.567 40 0.000112 680,000

Sod Farms 0.567 80 0.000223 340,000

Typical Field Crops 0.442 80 0.000174 440,000

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 Exposure and Risk Estimates for Isofetamid.

Exposure Scenario Crop or Targeta

Baseline 

Inhalation 

Unit 

Exposureb

Maximum

Application 

Ratec

Area 

Treated or 

Amount 

Handled 

Dailyd

Baseline Inhalation

Dosee MOEf

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 0.000650lb ai/gal

40

gallons 0.000113 680,000

M/L/A Liquids for 

MechanicallyPressurized 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 Crops” 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 mitigation = Baseline.

c Based on the maximum application rates on the proposed labels (Reg. Nos. 71512-EE and 71512-EG).

d Exposure Science Advisory Council Policy #9.1.

e Inhalation Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or 

Amount Handled Daily (A or gal/day) ÷ BW (69 kg).

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-Application 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 reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure.

Although isofetamid is persistent in soil, an 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/Risk Estimates

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

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

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

pesticides. The agency sought expert advice and input on issues related to volatilization of 
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 Analysis (http://www.regulations.gov/#!docketDetail;D=EPA-HQOPP-2014-0219). During Registration Review, the agency will utilize this analysis to determine 

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

required for isofetamid.

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.

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 postapplication

inhalation exposure scenarios. Furthermore, inhalation exposure during dusty mechanical 

activities such as shaking and mechanical harvesting is another potential source of postapplication inhalation exposure. However, the airblast applicator scenario is believed to 

represent a reasonable worst case surrogate estimate of post-application inhalation exposure 

during these dusty mechanical harvesting activities. The non-cancer inhalation risk estimate for 

commercial airblast application is not of concern (i.e. 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 hours for the REI. Thus, the 12-hour REI on the proposed labels 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 = exposure (mg ai/day),

UE = unit exposure (μg ai/lb ai),

AR = maximum application rate according to proposed label (lb ai A or lb ai/gal), and

A = area 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 = exposure (mg ai/day),

AF = absorption factor (dermal and/or 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 are compared to the 

appropriate POD (i.e., NOAEL) to assess the risk to occupational handlers for each exposure 

route. All MOE values are calculated using the following formula:

MOE= 

POD

ADD

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).