Date:

Subject: UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

May 14

, 2014 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

NICOSULFURON. Occupationa l and Residential Exposure Assessment for a Proposed Use on Sorghum

PC Code: 129008 Decision No

. : 473409 DP Barcode: D417841 Registration Nos.: 352-560, 352- 816,353-535 Petition No.: 2F8132 Regulatory Action: Section 3 Case No.: 7227 Risk Assessment Type: OccupationaVResidentia1 Exposure Assessment TXRNo.:NA CAS No

. : 111991-09-4 40 CFR: 180.45 4 MRIDN o.: NA

From:

Through:

To:

Introduction Kristin Rury, Biologist

# ·~~ Risk Assessment Branch

## (~) III 

# G

Health Effects Division (7509P)

Barry O'Keefe, ORE Team Leader 

# B< 0 l)/o 4 

### J_, Risk Assessment Branch (RAB) III r

### ~ Health Effects Division (7509P)

and

Kelly Lowe, Environmental Scientist

# A~~{f.r**ftdyi"~)** Monica Hawkins, Environmental

## Scie/i~**o/l~ ~**  Exposure Science Advisory Committee (ExpoSAC) I ED

Min dy Ondish Herbicide Branch Registration Division (7505P)

The Registration Division (RD) requested that the Health Effects Division (HED) conduct an exposure and risk assessment for the proposed use of nicosulfuron on sorghum that is tolerant of 

### acetolactate synthase (ALS) herbicides. Nicosulfuron is currently regi stere d for use on ALSherbicide tolerant sorgh um in seed propagation fields; however the exposure and risk resulting

Page I of 18from occupational use on sorghum was not previously assessed. Therefore

, HED has evaluated the occupational exposure and risk for nicosulfuron use on sorghum using up-to -dat e occupatio nal exposure assessment inpu ts and policies.

It is HED policy to use the best availab le data to assess exposure

. Several sources of generic data were used i n this assessment as surrogate data in the absence of chemical-spec ific data, including: Pesticide Handlers Exposure Database Version 1.1 (P H ED 1.1 ); the Agricu l tural Handler Exposure Task Force ( AHETF) database ; the Agricultural Reentry Task Force (AR T F) database. Some of these data are proprietary

, and subject to the data protection provisions of the Federal Insecticide

, Fungicide, and Rodenticide Act (FIFRA).

Note: This memorandum was reviewed by the Exposure Science Advisory Comm i ttee (ExpoSAC) on October 31, 2013.

Page 2 of 18Page 3 of 18 Table of Contents

1.0 Executive Summary

................................ ................................ ................................ ............. 4 2.0 Risk Assessment Conclusions and Summary of Risk Estimates

................................ ......... 6 3.0 Hazard Characterization

................................ ................................ ................................ ....... 6 4.0 Use Profile

................................ ................................ ................................ ........................... 7 5.0 Residential Exposure and Risk Estimates

................................ ................................ ............ 8 5.1 Spray Drift

................................ ................................ ................................ ........................ 8 5.2 Residentia l Bystander Post

- Application Inhalation Exposure

................................ ......... 8 6.0 Occupational Exposure and Risk Estimates

................................ ................................ ........ 9 6.1 Occupational Handler Exposure/Risk Estimates

................................ .............................. 9 6.2 Occupational Post

- application Exposure/Risk Estimates

................................ .............. 13 6.2.1 Occupational Post

- application Inhalation Exposure/Risk Estimates

...................... 13 6.2.2 Occupational Post

- application Dermal Exposure/Risk Estimates

.......................... 13 Appendix A. Summary of Occupational and Residential Non

- cancer Algorithms

..................... 16Page 4 of 18

1.0 Executive Summary

The active ingredient (ai), n icosulfuron

, is a sulfonylurea herbicide. It inhibits the action of an enzyme unique to plants, acetolactate synthase (ALS)

, leading to the disruption of cell division and plant growth. ALS is not found in humans or mammals. Nicosulfuron is registered for use on field corn, sweet corn, popcorn, and grasses (Bermuda grass, grass forage

, and grass ha y). It is also registered for use on sorghum plants in seed propagation fields. When applied to sorghum resistant to ALS

- inhibitors, the surrounding weeds will be controlled. However, when applied to sorghum that is not resistant to ALS

- inhibitor herbi cides, the plant itself will be eliminated. Additional time

- limited tolerances (Section 18 exemptions) of nicosulfuron on Bermuda grass forage and hay expired in December 2011. Nicosulfuron has no registered residential uses.

DuPont Crop Protection (D uPontTM) submitted a petition (PP# 2F8132 ) to allow nicosulfuron use

on sorghum tolerant to ALS herbicides. Nicosulfuron is currently registered for use on sorghum grown for seed and resistant to ALS herbicides, but the occupational exposure risk ha s not be en previously evaluated. Therefore, HED has evaluated the exposure risk from nicosulfuron use on sorghum using current occupational exposure policies and inputs. The proposed uses will be added to the technical product label ( DuPontTM Nicosulfuron Technic al, EPA Reg. No. 352

- 535) and to the formulated end use product label s (DuPontTM Steadfast ® XP herbicide, EPA Reg. No. 3520

- 816

, and DuPontTM Accent ® herbicide, EPA Reg. No. 352

- 560 ). Both formulated end

- use products are water dispersible granular (WG) form ulation s containing 30% and 75% nicosulfuron by weight , respectively

. DuPontTM Steadfast ® XP herbicide (EPA Reg. No. 352

- 816) also contains the ai rimsulfuron. Exposure to rimsulfuron from the proposed use on sorghum will be evaluated in a separate docume nt.

Proposed Use Profile Nicosulfuron has been proposed for use on ALS

- tolerant sorghum that is less than 20 inches tall. Nicosulfuron may be applied with aerial and ground equipment; chemigation is prohibited. DuPontTM Steadfast ® XP herbicide (EPA Reg. No. 352

- 816) may be applied twice per year, with single application rates ranging from 0.023

- 0.031 lb ai/A, with a maximum seasonal application rate of 0.031 lb ai/A. DuPontTM Accent ® herbicide (EPA Reg. No. 352

- 560) may be applied twice per year, with single application rates ranging from 0.031

- 0.062 lb active ingredient (ai) /A

, with a maximum seasonal application rate of 0.084 lb ai/A.

The proposed label s require occupational handlers to wear long pants, long sleeved shirts, che mical resistant gloves, shoes , and socks. The restricted entry inter val (REI) on the proposed labels is 4 hours. There are no proposed or registered residential uses of nicosulfuron

. Chemigation is not permitted on the proposed labels. Because nicosulfu ron is an herbicide, and the proposed label specifies broadcast, banded, and over

- the

- row applications to sorghum, the use of handheld equipment is not expected for nicosulfuron and exposure from mixing/loading/applying using handheld equipment was not ass essed.Page 5 of 18

Exposure Profile Based on application rate and label information, only short

- and intermediate

- term exposure is expected for occupational handlers and post

- application workers. Chronic exposure is not expected for the proposed use pattern

.

Hazard Concerns Subchronic or chronic dietary administration of doses exceeding the limit dose did not produce adverse effects in rats or mice. Chronic dietary administration at the limit dose to dogs produced mild effects (decreased body weight gains in males and increases in the relative liver and kidney weights). Nicosulfuron is classified as “not likely to be carcinogenic to humans.” Nicosulfuron exhibits low acute mammalian toxicity via oral, dermal and inhalation routes of exposure (Category III or IV for acute lethality and irritation studies) and is not a dermal sensitizer. Estimated short

- and intermediate

- term dermal and inhalation exposures were compared to the oral point of departure (POD) based on decreased body weight gain in males and t he statistically significant increase in relative liver and kidney weights of males in the one year dog study. Dermal and inhalation exposures were assumed to be equivalent to oral exposures. The endpoint selected is based on developmental or fetal effec ts; therefore, a 69 kg body weight was used in the calculations. Since the last risk assessment, the Agency has received the acute and subchronic neurotoxicity studies, and the required immunotoxicity study. Nicosulfuron was not shown to be neurotoxic or immunotoxic. The Agency waived the requirement for the subchronic dermal and subchronic inhalation toxicity studies (TXR# 0050011 ). HED presently has sufficient information to evaluate the hazards associated with exposure to nicosulfuron at this time

. The Food Quality Protection Act (FQPA) safety factor has been reduced (i.e., from 10X to 1X). The level of concern for dermal and inhalation risk assessment is a margin of exposure (MOE) of 100 (i.e. an MOE < 100 is of concern).

Based on the Agency's current practices, a quantitative occupational post

- application inhalation exposure assessment was not performed for nicosulfuron at this time. If new policies or procedures are put into place, the Agency may revisit the need for a q uantitative occupational post

- application inhalation exposure assessment for nicosulfuron

.
Occupational Handler Exposures and Risk Estimates There are no occupational handler risk estimates of concern for the proposed uses of nicosulfuron at baseline (no personal protective equipment; PPE ). At baseline, all short

- and intermediate

- term occupational handler combined (dermal + inhalation) MOEs ranged from 490
to 56 ,000

.
Occupational Post

- Application Exposures and Risk Estimates The occup ational short

- term post

- application risk estimates resulted in dermal MOEs of 30 ,000 on the day of application and was not a risk of concern

.

Human Studies Review This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. These data, which include studies from PHED 1.1; the AHETF database; and the ARTF database; are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that review, and (3) are co mpliant with applicablePage 6 of 18

ethics requirements. For certain studies, the ethics review may have included review by the Human Studies Review Board. Descriptions of data sources, as well as guidance on their use, can be found at the Agency website 1

.

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

- cancer occupational post

- application inhalation exposure assessment was not performed for nicosulfuron 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 nicosulfuron

.

2.0 Risk Assessment Conclusions and Summary of Risk Estimates

There were no risk estimates of concern for occupational handlers of nicosulfuron at baseline (no PPE), nor were there any occupational post

- application risk estimates of concern at day 0 from nicosulfuron use on sorghum.

At baseline, all short

- and intermediate

- term occupational handler combined (dermal + inhalation) margins of exposure ( MOEs ) ranged from 490 to 56 ,000. The post

- application MOE

was 30 ,000 on the day of application (day 0).

3 .0 Hazard Characterization

Acute Toxicity Nicosulfuron exhibits low acute toxicity via the oral (Toxicity Category IV), dermal (Toxicity Category III), a nd inhalation (Toxicity Category IV) routes of exposure. It is a moderate eye irritant (Toxicity Category III), not a dermal irritant (Toxicity Category IV), and is not a dermal sensitizer.

Table 3 .1

. Acute Toxicity Profile

– Nicosulfuron.

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral

– rat 40924205 LD 50 > 5000 mg/kg IV

870.1200 Acute dermal

– rabbit 40924207 LD 50 ≥ 2000 mg/kg III

870.1300 Acute inhalation

– rat 40924209 LC 50 ≥ 5.9 mg/L IV

870.2400 Acute eye irritation

– rabbit 41082602 Moderate eye irritant III

870.2500 Acute dermal irritation

– rabbit 41082603 Not irritant IV

870.2600 Skin sensitization

– guinea pig 41082604 Not a sensitizer NA

Toxicological PODs Used for Risk Assessment Subchronic or chronic dietary administration of doses exceeding the limit dose did not produce adverse effects in rats or mice. Chronic dietary administration at the limit dose to dogs produced

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

- exposure

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

- app

- exposure

- data.htmlPage 7 of 18

mild effects (decreased body weight gains in males and increa ses in the relative liver and kidney weights). Nicosulfuron is classified as “not likely to be carcinogenic to humans.”

Estimated short

- and intermediate

- term dermal and inhalation exposures were compared to the oral POD (no observed adverse effect lev el; NOAEL = 125 mg/kg/day) based on decreased body weight gain in males and the statistically significant increase in relative liver and kidney weights of males seen at the lowest observed adverse effect level (LOAEL) of 500 mg/kg/day in the one year dog s tudy. HED presently has sufficient information to evaluate the hazards associated with exposure to nicosulfuron at this time . The FQPA safety factor has been reduced (i.e., from 10X
to 1X). The level of concern for dermal and inhalation risk assessment is a MOE of 100 (i.e. an MOE < 100 is of concern).

Table 3 .2

. Summary of Toxicological Doses and Endpoints for Nicosulfuron for Use in Occupational Human Health Risk Assessments

. Exposure/ Scenario Point of

Departure Uncertainty

Factors Level of Concern

for Risk Assessment Study and Toxicological Effects

Dermal Short

- (1

- 30 days) and Intermediate

- (1

- 6 months) Term NOAEL

=125 mg/kg/day

DAF = 100% (default) UF A =10x

UF H =10x Occupational

LOC for MOE < 100 Chronic oral study in dogs.

LOAEL = 500 mg/kg/day based on increased relative liver and kidney weights in males. Supported by rabbit developmental toxicity study (NOAEL = 100 mg/kg/day, LOAEL 500 mg/kg/day).

Inhalation Short

- (1

- 30 days) and Intermediate

term (1

- 6 months)

Term NOAEL

=125 mg/kg/day

IAF = 100% (default) UF A =10x

UF H =10x Occupational

LOC for MOE < 100 Chronic oral study in dogs.

LOAEL = 500 mg/kg/day based on increased relative liver and kidney weights in males. Supported by rabbit developmental toxicity study (NOAEL =
10 0 mg/kg/day, LOAEL 500 mg/kg/day).

Cancer (oral, dermal, inhalation) Classification: “Not likely to be Carcinogenic to Humans” based on lack of tumorigenic

effects in rodent (rats and mice) bioassays at the limit doses and lack of mutagenic effects in the in vitro and in vivo genotoxicity assays. 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 adver se effect lev el. 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). MOE = margin of exposure . LOC = level of concern. N/A = not applicable. DAF = dermal absorption factor. IAF = Inhalation absorption factor.

Absorption : A dermal absorption factor was not used for the exposure assessment. Since no inhalation or dermal absorption data are available, toxicity by the dermal and inhalation route s is considered to be equivalent to the estimated toxicity by the oral route of exposure.

Body Weight : Since the dermal and inhalation PODs are based on developmental and/or fetal

e ffects, the body weight appropriate for dermal and inhalation assessments is 69 kg.

4 .0 Use Profile

A summary of the proposed use pattern is shown in Table 4.0.Page 8 of 18

Table 4

. 0 . Summary of Directions for Use of Nicosulfuron

. Applic. Timing, Type, and Equip. Formulation

[EPA Reg. No.] Applic.

Rate (lb ai/A) Max. No.

Applic. per Season Max.

Seasonal Applic. Rate (lb ai/A) PHI

(days) Use Directions and

Limitations

Sorghum

Ground, Aerial Dupont TM

Steadfast ® XP Herbicide EPA Reg. No. 352

- 816 30% ai (nicosulfuron) by weight 0.023

-

0.031 0.031 2 7 Do not apply to sorghum taller than 20”. Do not graze livestock or cut for forage within 48 days of application. Do not harvest for grain or stover within 69 days of application. DupontTM Accent® Herbicide EPA Reg. No. 352

- 560 75% ai by weight 0.031

-

0.062 2 0.084 7

5 .0 Residential Exposure and Risk Estimates

There are no proposed or registered residential uses of nicosulfuron at this time ; therefore, a residential exposure assessment has not been conducted.

5

. 1 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 nicosulfuron

. The Agency has been working with the Spray Drift Task Force (a task force composed of various registrant s 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). 2 The Agency is also taking means to qualitatively and qualitatively address spray drift as a potential source of exposure in risk assessments for pesticides through existing programs such as Ag Drift and chemical specific properties of pest icides. 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.

5

. 2 Residential Bystander Post

- Application Inhalation Exposure

Based on the Agency's current practices, a quantitative post

- application inhalation exposure assessment was not performed for nicosulfuron at this time primarily because of the low acute

2 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htmPage 9 of 18

inhalation toxicity (Toxicity Category IV), low vapor pressure (1.2 x 10

- 16 mm Hg at 25oC), and the low proposed use rate (0.062 lb ai/A). However, volatilization of pesticides may be a source of post

- application inhalation exposure to individuals nearby pesticide applications. The Agency sought exper t 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 3 . The Agency is in the process of evaluating the SAP report and may, as appropriate, develop policies and procedures to identify the need for and, subsequently, the way to incorporate post

- application inhalation exposure into the Agency's risk assessments. If new policies or p rocedures are developed, the Agency may revisit the need for a quantitative post

- application inhalation exposure assessment for nicosulfuron.

6 .0 Occupational Exposure and Risk Estimates

6 .1 Occupational Handler Exposure/Risk Estimates

HED uses the te rm 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 requi rements (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 uses. The quantitative exposure/risk assessment developed for occupational handlers is based on the following scenarios:

 Mixing/Loading dry flowable formulations for aerial application;

 Mixing/Loading dry flowable formulations for groundboom application;

 Applying sprays with aerial equipment;

 Applying sprays with groundboom equipment; and

 Flagging for aerial applications.

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 : A summary of the proposed application rates is provided in Table 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, u sed 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

3 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.htm lPage 10 of 18

data are proprie tary (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 Pesticid e Handler Unit Exposure Surrogate Reference Table 4 ”, 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 website 5

.

Area Treated or Amount Handled : Based on HED ExpoSAC Policy 9.1, the amount treated or handled per day was assumed to be:

 1200 acres for mixing/loading for aerial application ;

 200 acres for mixing/loading for groundboom application;

 1200 acres for aerial application ;

 200 acres for groundboom application; and

 350 acres for flagging for aerial application

. 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 c lients within a region). For nicosulfuron , based on the proposed use, short

- and intermediate

- term exposure s are expected . Sorghum is grown on large

scale farms it is likely that a commercial applicator could apply nicosulfuron over a longer period of ti me. Additionally, for both dermal and inhalation exposures, the PODs selected are considered protective of both durations.

Mitigation/Personal Protective Equipment: Estimates of dermal and inhalation exposure were calculated for various levels of perso nal protective equipment (PPE). 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, as well as baseline with various levels of PPE as necessary (e.g., gloves, respirator, etc). The proposed label requires occupational handlers to wear long pants, long sleeved shirts, chemical resistant gloves, shoes, and socks.

Occupational Handler Non

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

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

.
Combining Exposures/ Risk Estimates :

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

- exposure

- table.pdf

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

- exposure

- data.htmlPage 11 of 18

Dermal and inhalation risk estimates were combined in this assessment, since the toxicological effects for these exposure routes were similar. Dermal and inhalation risk estimates were combined using the following formula:

Total MOE = Point of Departure (mg/kg/day) ÷ Combined dermal + inh alation dose (mg/kg/day)

Summary of Occupational Handler Non

- Cancer Exposure and Risk Estimates There are no risk estimates of concern at baseline (no PPE). At baseline, the short

- and intermediate

- term combined (dermal + inhalation) occupational handler MOEs ranged from 490
to 56 ,000.

The Agency matches quantitative occupational exposure assessment with appropriate characterization of exposure potential. While HED presents quantitative risk estimates for human flaggers where appropriate, agricultural aviation has changed dramatically over the past two decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of their membership, the use of GPS for swath guidance in agricultural aviation has grown steadily from the mid 1990’s. Over the same time period, the use of human flaggers for aerial pesticide applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent (2012) NAAA survey. The Agency will continue to monitor all available information sour ces to best assess and characterize the exposure potential for human flaggers in agricultural aerial applications.

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

- sleeve shirt, long pants, shoes, and socks); per the Agency’s Worker Protection Standard stipulations for engineering controls, pilots are not required to wear protective gloves for the duration of the application . With this level of protection, there are no risk estimates of concern for applicators.Page 12 of 18

Table 6 .1. 1. Occupational Handler Short

- and Intermediate

- Term Exposure and Risk Estimates for Nicosulfuron

.

Exposure Scenario Crop or Target Dermal Unit

Exposure ( μ g/lb ai) 1 Inhalation Unit

Exposure ( μ g/lb ai) 1 Maximum

Application Rate 2 Area Treated or Amount Handled Daily 3 Dermal Inhalation Total

Baseline* Baseline* Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 MOE 8

Mixer/Loader Mixing/Loading for Aerial Application Sorghum 227 8.96 0.062 1200 acres 0.2 5 510 0. 0097 1 3 ,000 490

Mixing/Loading for Groundboom Application Sorghum 227 8.96 0.062 200 acres 0. 047 3, 100 0.001 6 78 ,000 3, 0 00

Applicator Applying with Aerial Equipment Sorghum 2.08 0.0049 0.062 1200 acres 0. 0023 56 ,000 0. 0000053 2 4 ,000,000 56 ,000

Applying with Groundboom Equipment Sorghum 78.6 0.34 0.062 200 acres 0. 014 8,9 00 0. 000061 2, 0 00,000 8

, 9 00

Flagger Flagging for Aerial Application Sorghum 11 0.35 0.062 350 acres 0.003 5 36 ,000 0. 00011 1, 1 00,000 35 ,000

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” ( May 2013 ); Level of mitigation: Baseline. *Aerial Application is assessed assuming a closed cockpit (engineering controls).

2 Based on registered or proposed label (Reg. No. 352

- 560 ). This exposure assessment is protective of the DupontTM Steadfast ® XP Herbicide label because the proposed application rate is lower than 0.062 lb ai/A. 3 Exposure Science Advisory Council Policy #9.1. 4 Dermal 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 (A or gal/day) × DAF ( 100 %) ÷ BW ( 69 kg). 5 Dermal MOE = Dermal NOAEL ( 125 mg/kg/day) ÷ Dermal Dose (mg/kg/day). 6 Inhalation Dose = Inhalation Unit Exposure ( μ g/lb ai) × Conversion Fac tor (0.001 mg/ μ g) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ BW ( 69 kg). 7 Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). 8 Total MOE = NOAEL (mg/kg/day) ÷ Dermal Dose + Inhalation Dose.Page 13 of 18

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 re

entry exposure). Such exposures may occur when workers enter previously treated areas to perform job functions, including activities related to crop production, such as scouting for pests or harvesting. Post

- application exposure levels vary over time and depend o n 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.

6

. 2 .1 Occupational Post

- application Inhalation Exposure/Risk Estimates

Based on the Agency's current practices, a quantitative post

- application inhalation exposure

ass essment was not performed for nicosulfuron at this time primarily because of the low acute inhalation toxicity (Toxicity Category IV), low vapor pressure ( 1.2 x 10

- 16 mm Hg at 25oC ), an d the low proposed use rate (0.062 lb ai/A). However, there are multip le 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 tha t contain pesticides. The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final r eport on March 2, 2010 6

. The Agency is in the process of evaluating the SAP report as well as available post

- application inhalation exposure data generated by the ARTF and may, as appropriate, develop policies and procedures, to identify the need for and, subsequently, the way to incorporate occupational post

- application inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post

- application inhalation exposure assessment for nicosulfuron

.
Although a quantitative occupational post

- application inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercial handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in higher exposure than post

- application exposure. Therefore, it is expected that these handler inhalation exposure estimates would be protective of most occupational post

- application inhalation exposure scenarios.

6

. 2 .2 Occupational Post

- application Dermal Exposure/Risk Estimates

Occupational Post

- application Dermal Exposure Data and Assumptions

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

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

6 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.htmlPage 14 of 18

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

- term and exposures 30 days to six months as intermediate

- term. For nicosulfuron, both short

- and intermediate

- term exposure could occur for the proposed use on sorghum. However, because the POD is the same for dermal short

- and interm ediate

- term exposures, one assessment is protective of both durations. Furthermore, o nly exposure from scouting was assessed because nicosulfuron is an herbicide. Hand weeding, the only other post

- application exposure scenario quantitatively considered a ssociated with sorghum would not be necessary following application of an herbicide. While nicosulfuron is only applied early in the sorghum growth stage before the plant reaches 20” high, t he assessment is also protective of exposure from scouting late i n the crop season when foliage is full

. Therefore, the assessment is considered a conservative estimate of post

- application exposure to treated sorghum.

Transfer Coefficients : It is the policy of HED to use the best available data to assess post

applica tion exposure. Sources of generic post

- application data, used as surrogate data in the absence of chemical

- specific data, are derived from ARTF exposure monitoring studies, and, as proprietary data, are subject to the data protection provisions of FIFRA. The standard values recommended for use in predicting post

- application exposure that are used in this assessment, known as “transfer coefficients”, are presented in the ExpoSAC Policy 3 7 ” which, along with additional information about the ARTF data, can be found at the Agency website 8

.

Table 6

. 2 .2

. 1

. Anticipated Post

- Application Activities and Dermal Transfer Coefficients.

Proposed Crops Policy Crop Group Category Crop

Height Foliage

Density Transfer

Coefficients (cm 2 /hr ) Activities

Sorghum, grain Field/Row

Crop/Tall High &

Low Full &

Min 210 Scouting

Application Rate: Application rates are provided in Table 4.0.

Exposure Time : The average occupational workday is assumed to be 8 hours.

Dislodgeable Foliar Residues : In accordance with the updated Part 158 data requirements (2007), one or more DF R stud ies are required when a pesticide has residential or occupational
uses t hat could result in post

- application dermal exposure. As part of the recent revision to the Health Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment , HED analyzed a number of DFR studies and selected a new def ault value for the fraction of the application rate available to be dislodged after a foliar application (F AR ). This default value is 25 % and is based on an analysis of 19 DFR studies where the F AR value ranged from 2% to 89%. This value is recommended f or use in both residential and occupational post

- application assessments. Of the analyzed DF R studies, the maximum F AR value seen was 89% or 3.6 times higher than the default residue transfer value. Therefore, the HED has decided that a calculated MOE of approximately 4 times higher than the level of concern (e.g., an MOE > 400 if the LOC = 100) using the default dislodged residue values would provide an adequate margin of safety for any potentially higher residues seen in a chemical

- specific DFR study

7 Available: http://www.epa.gov/pesticides/science/exposac_policy3.pdf

8 Available: http://www.epa.gov/pesticides/science/post

- app

- exp osure

- data.htmlPage 15 of 18

( G uidance for Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar Residue (DFR) Studies

. 12 / 12 /2012, Exposure Science Advisory Council ). A DF R study is not required for nicosulfuron at this time since the dermal MOE s are greater than 4 times the LOC based on default values for the fraction of application rate available for transfer after a foliar application.

Chemical

- specific dislodgeable foliar residue data have not been submitted for nicosulfuron

. Therefore, this assessment uses HED’s default assumption that 25% of the application is available for transfer on day 0 following the application and the residues dissipate at a rate of 10% each following day.

Occupational Post

- application Non

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

- cancer exposure and dose for occupational post

- application workers can be found in Appendix A

.
Occupational Post

- application Non

- Cancer Dermal Risk Estimates The occupational short

- term post

- application risk assessment resulted in a dermal MOE of 30 ,000 on the day of application. Therefore, there are no post

- application risk estimates of concern for nicosulfuron.

Table 6

. 2 .2.2

. Occupational Post

- application Non

- Cancer Exposure and Risk Estimates for Nicosulfuron

.
Crop/Site Activities Transfer Coefficient (cm 2 /hr) DFR/TTR 1 Dermal Dose (mg/kg/day) 2 MOE 3

Short

- and Interm e diate

- term
Sorghum Scouting 210 0.17 0. 0042 30 ,000

1 DFR = Application Rate × F × (1

- D) t × 4.54E8 μg/lb × 2.47E

- 8 acre/cm 2 ; where F = 0.25 and D = 0.10 per day

. 2 Daily Dermal Dose = [DFR (μg/cm 2 ) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption ( 100 %)]  BW ( 69 kg). 3 MOE = POD ( mg/kg/day) / Daily Dermal Dose.

Restricted Entry Interval Nicosulfuron is classified as Toxicity Category III or IV based upon data for acute dermal toxicity, acute inhalation toxicity, primary skin irritation, and primary eye irritation. Typically, the REI specified on the proposed label is based on the acute toxicity of the a ctive 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 12

- hour REI. However, it is noted that the proposed product label has a 4

- hr REI listed. REIs may be further reduced from 12 hours if certain criteria are met for both the technical material and the different end

- use products in accordance with the Pesticide Registration (PR) Notice 95

- 3 [Reduction of Worker Protection Standard (WPS) Interim Restricted Entry Intervals (REIs) for Certain Low Risk Pesticides] 9

. Based only on the acute toxicity categories, nicosulfuron is a possible candidate for a 4

- hr REI, however, RD should ensure that the additional criteria listed in PR Notic e 95

- 3 are met for the active ingredient and the end

- use product.

9 Available: http://www.epa.gov/PR_Notices/pr95

- 3.htmlPage 16 of 18

Appendix A. Summary of Occupational and Residential Non

- cancer Algorithms

Occupational Non

- cancer Handler Algorithms

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 (μ g 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 a bsorbed in a given scenario (mg ai/ kg / day), E = e xposure (mg ai/day), AF = absorption fa ctor (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. T he 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
ADD

where:

MOE = m argin of e xposure: value used by HED to represent risk estimates (unitless), POD = p oint of d eparture (mg/kg/day)

, and ADD = average daily dose absorbed in a given scenario (mg ai/kg/day)

.
Occupational Non

- cancer Post

- application AlgorithmsPage 17 of 18

Potential daily exposures for occupational post

- application workers are calculated using the following formulas:

DFR t =AR * F* (1

- D) t * ( 4.54E8 ug lb ) * ( 2.47E

- 8 A

cm 2 )

where:

DFR t = dislodgeable foliage residue on day "t" (μg/cm 2 ), AR = a pplication r ate (lb ai/acre), F = fraction of ai retained on foliage or 25% (unitless), D = fraction of residue that dissipates daily or 10% (unitless), and
t = number of days after application day (days)

.

E=TC * DFR t * ET * 0.001 mg

ug

where: E = e xposure (mg ai/day), TC = t ransfer coefficient (cm 2 /hr), DFR t = d islodgeable f oliar r esidue on day “t” (μg/cm 2 ), and ET = e xposure t ime (hours/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/or inhalation), and BW = body weight (kg).

Margin of Exposure: Non

- cancer risk estimates for each 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 dose received by occupational post

- application workers is compared to the appropriate POD ( i.e.

, NOAEL) to assess the risk to occupational post

- application workers

. All MOE values a re calculated using the following formula:

MOE= POD
ADD

where:Page 18 of 18

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