Date: 

Subject: 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

May 14, 2014 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

NICOSULFURON. Occupational 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 

Risk Assessment Type: OccupationaVResidentia1 Exposure Assessment Case No.: 7227 

TXRNo.:NA CAS No.: 111991-09-4 

MRIDNo.: NA 40 CFR: 180.454 

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.rftdyi"~) 

Exposure 

Monica Hawkins, 

Science 

Environmental 

Advisory Committee 

Scie/i~ (ExpoSAC) o/l~ I ED ~ 

Mindy 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 registered for use on ALSherbicide tolerant sorghum in seed propagation fields; however the exposure and risk resulting 

Page I of 18 
from 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-date 

occupational exposure assessment inputs and policies. 

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 Agricultural Reentry Task Force (ARTF) 

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 Committee 

(ExpoSAC) on October 31, 2013. 

Page 2 of 18 
Page 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 Residential 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..................... 16
Page 4 of 18

1.0 Executive Summary

The active ingredient (ai), nicosulfuron, 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 hay). 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 herbicides, 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 (DuPontTM) 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 has not been 

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 Technical, EPA Reg. No. 352-535) 

and to the formulated end use product labels (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) formulations 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 document. 

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 labels require occupational handlers to wear long pants, long sleeved shirts, 

chemical resistant gloves, shoes, and socks. The restricted entry interval (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 nicosulfuron 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 assessed. 
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 the 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 effects; 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 quantitative 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 occupational 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 compliant with applicable 
Page 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 website1. 

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), and 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 LD50 > 5000 mg/kg IV

870.1200 Acute dermal – rabbit 40924207 LD50 ≥ 2000 mg/kg III

870.1300 Acute inhalation – rat 40924209 LC50 ≥ 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.html
Page 7 of 18

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.” 

Estimated short- and intermediate-term dermal and inhalation exposures were compared to the 

oral POD (no observed adverse effect level; 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 study. 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) 

UFA=10x

UFH=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 

Intermediateterm (1-6 

months)

Term 

NOAEL

=125

mg/kg/day

IAF = 

100% 

(default) 

UFA=10x

UFH=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).

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 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). 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 routes 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 

effects, 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 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). 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 

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. 

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.htm 
Page 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 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, 20103. 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 procedures 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 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 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, 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 

 

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

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 Table4”, 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 website5.

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 clients within a region). For nicosulfuron, based on the 

proposed use, short- and intermediate-term exposures are expected. Sorghum is grown on largescale farms it is likely that a commercial applicator could apply nicosulfuron over a longer 

period of time. 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 personal 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 Equations

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.html
Page 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 + inhalation 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 sources to 

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

applications.

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

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

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

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

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

level of protection, there are 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 (μg/lb 

ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Baseline* Baseline* Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

Mixer/Loader

Mixing/Loading for Aerial 

Application Sorghum 227 8.96 0.062 1200 acres 0.25 510 0.0097 13,000 490

Mixing/Loading for 

Groundboom Application Sorghum 227 8.96 0.062 200 acres 0.047 3,100 0.0016 78,000 3,000

Applicator

Applying with Aerial 

Equipment Sorghum 2.08 0.0049 0.062 1200 acres 0.0023 56,000 0.0000053 24,000,000 56,000

Applying with 

Groundboom Equipment Sorghum 78.6 0.34 0.062 200 acres 0.014 8,900 0.000061 2,000,000 8,900

Flagger

Flagging for Aerial 

Application Sorghum 11 0.35 0.062 350 acres 0.0035 36,000 0.00011 1,100,000 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 (μg/lb ai) × Conversion Factor (0.001 mg/μg) × 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 (μg/lb ai) × Conversion Factor (0.001 mg/μg) × 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 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.

6.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates

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 

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, there are multiple potential sources of postapplication inhalation exposure to individuals performing post-application activities in 

previously treated fields. These potential sources include volatilization of pesticides and 

resuspension of dusts and/or particulates that contain pesticides. The Agency sought expert 

advice and input on issues related to volatilization of pesticides from its Federal Insecticide, 

Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and 

received the SAP’s final report on March 2, 20106. 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.html
Page 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 intermediate-term exposures, one assessment is protective of both 

durations. Furthermore, only exposure from scouting was assessed because nicosulfuron is an 

herbicide. Hand weeding, the only other post-application exposure scenario quantitatively 

considered associated 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, the assessment is also protective of exposure from scouting late in 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 postapplication 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 37” which, along with 

additional information about the ARTF data, can be found at the Agency website8.

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 

(cm2/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 DFR studies are required when a pesticide has residential or occupational 

uses that 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 default value 

for the fraction of the application rate available to be dislodged after a foliar application (FAR). 

This default value is 25% and is based on an analysis of 19 DFR studies where the FAR value 

ranged from 2% to 89%. This value is recommended for use in both residential and occupational 

post-application assessments. Of the analyzed DFR studies, the maximum FAR 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-exposure-data.html
Page 15 of 18

(Guidance for Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar 

Residue (DFR) Studies. 12/12/2012, Exposure Science Advisory Council). A DFR study is not 

required for nicosulfuron at this time since the dermal MOEs 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 

(cm2/hr) DFR/TTR1 Dermal Dose (mg/kg/day)2 MOE3

Short- and Intermediate-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/cm2; where F = 0.25 and D = 0.10 per day. 

2 Daily Dermal Dose = [DFR (μg/cm2) × 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 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 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 Notice 95-3 are met for the active ingredient and the end-use product.

 

9 Available: http://www.epa.gov/PR_Notices/pr95-3.html
Page 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 = 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).

Occupational Non-cancer Post-application Algorithms
Page 17 of 18

Potential daily exposures for occupational post-application workers are calculated using the 

following formulas:

DFRt=AR * F* (1-D)t* (4.54E8

ug

lb) * (2.47E-8

A

cm2

)

where:

DFRt = dislodgeable foliage residue on day "t" (μg/cm2),

AR = application rate (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 = exposure (mg ai/day),

TC = transfer coefficient (cm2/hr),

DFRt = dislodgeable foliar residue on day “t” (μg/cm2), and

ET = exposure time (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 = 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 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 are 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 (unitless),

POD = point of departure (mg/kg/day), and

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