UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

MEMORANDUM 

DA TE : September 14, 2015 

WASHINGTON, D.C. 20460 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Nicosulfuron. Human Health Draft Risk Assessment for Registration Review. 

PC Code: 129008 

Decision No.: 503825 

Petition No.: NA 

DP Barcode: D427029 

Registration Nos.: NA 

Regulatory Action: Registration Review 

Risk Assessment Type: Single Chemical Aggregate Case No.: 7227 

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

MRID No.: NA 40 CFR: § 180.597 

FROM: 

THROUGH: 

TO: 

Meheret 

Minerva 

Kristin Rury

Neguss

Mercado-Feliciano, 

, Bio

ie, 

log

Chem

ist 

ist lte/..c,.ye:f 

Toxicolog {1/ I- a-;~ 

~v.J 

~ 

~ 

Risk Assessment Branch III 

Health Effects Division (7509P) 

Christine Olinger, Chief ~~vj i----

Risk Assessment Branch Ill j:7 ( 

Health Effects Division (750 

Miguel Zavala, Chemical Review Manager 

Kelly Sherman, Risk Manager 

Risk Management and Implementation Branch III 

Pesticide Re-Registration Division (7508P) 

This document evaluates the existing uses of nicosulfuron as part of Registration Review and 

represents the draft risk assessment (ORA). Nicosulfuron is a sulfonylurea (SU) herbicide. The 

Agency is reviewing all the SU herbicides jointly under Registration Review. The endpoints and 

points of departure (PODs) for nicosulfuron have not changed since the previous risk assessment 

(K. Rury, 0408756, 06/26/2014). Some studies used for endpoint selection have conservative 

No Observed Adverse Effect Level/Lowest Observed Adverse Effect Level (NOAEL/LOAEL) 

values that have not been updated to reflect current standards for evaluating toxicity studies. 

Updates would result in higher NOAEL/LOAEL values and, given the current risk picture, 

would not impact the overall findings of the risk assessment. 
Nicosulfuron Human Health Risk Assessment DP No. D427029 

1.0 

2.0 

2.1 

2.2 

2.3 

3.0 

3. 1 

3.2 

3.3 

3.4 

4.0 

5.0 

5.1 

Table of Contents 

Executive Summary ...................................... ..................... .................................................. 3 

I-IED Recommendations ...................................................................................................... 3 

Tolerance Considerations ............................................................................................... .. 3 

Use Profile & Anticipated Exposure Pathways .................... ....... .............. ....................... 3 

Consideration of Environmental .Justice ..................................... ............................ ......... 5 

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

Summary of Toxicological Effects ...... .... .... ............. .... ... .... .............. .............. ................ 6 

Safety Factor for Infants and Children (FQPA Safety Factor) .... .............. ....................... 6 

Toxicity Endpoint and Point of Departure Selections ...................................................... 6 

Endocrine Disruption ....................................................................................................... 7 

Residue Chemistry ............................................................................................................... 8 

Dietary Risk Assess1nent ..................................................................... ................................ 9 

Water Residue Profile ........................ ................................ ....... .... .......... ....... .................. 9 

5.2 Dietary (Food + Water) Exposure Assessment.. .... ............... ............... ...... .................... I 0 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization .................................... I 0 

6.1 Spray Drift .. ....... .............. ............................................................................................... I 0 

6.1.1 Combined Risk Estimates From Lawn Deposition Adjacent to Applications ........ 12 

6.2 Residential Bystander Post-Application Inhalation Exposure ....................................... 13 

7.0 Aggregate Exposure/Risk Characterization ... ................................................ .................... I 3 

8.0 Cumulative Exposure/Risk Characterization ..................................................................... 14 

9.0 Occupational Exposure/Risk Characterization .. ............ .... .............. ........... ....... ....... ....... .. 14 

9.1 Occupational Handler Exposure ................. ............ .... .... .................. ... ........................... 14 

9.2 Occupational Post-Application Exposure ............... ....................................................... 17 

l 0.0 Public Health and Pesticide Epidemiology Data ............................................................... I 8 

I 1.0 References ...................................................... ............. ....... ................................................ 19 

Appendix A. Toxicology Profile ................................................................................................. 21 

A. I Toxicology Data Requirements ...................................................................................... 21 

A.2 Toxicity Profiles ............ ................................................................................................. 22 

Appendix B. Dietary Exposure/Risk Modeling Input and Output.. .............................................. 25 

Appendix C. Physical/Chemical Properties of Nicosulfuron and Metabolites ............................ 28 

Appendix D. Review of Human Research ............... ................................................................. ... 30 

Appendix E. International Harmonization .......................................... ....... .................................. 31 

Appendix F. DFR Data Waiver Rationale ................................................................................... 32 

Page 2 of 32 
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 3 of 32

1.0 Executive Summary

Nicosulfuron (2-[[[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfonyl]-N,N-dimethyl3-pyridinecarboxamide) is a systemic herbicide belonging to the sulfonylurea group of herbicides. 

It is currently 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, and on pastures, rangeland and non-crop areas. Since the last risk assessment (K. Rury, 

D408756, 06/26/2014) and the scoping document (K. Rury, D397347, 06/11/2012), there have 

been no changes to the nicosulfuron use, hazard, or residue profile. However, the existing uses 

have been reevaluated here using updated occupational and dietary exposure assessment 

methodologies. There are no risk estimates of concern for the existing uses of nicosulfuron.

2.0 HED Recommendations

2.1 Tolerance Considerations

Permanent US tolerances are established under 40 CFR §180.454 for residues of the herbicide 

nicosulfuron, 2-[[[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfonyl]-N,Ndimethyl-3-pyridinecarboxamide, in/on the following commodities: meat byproducts of cattle, 

goat, horse, and sheep at 0.05 ppm; the meat and fat of cattle, goat, horse and sheep at 0.01 ppm; 

milk at 0.01 ppm; corn commodities (field, pop, sweet) at 0.1 ppm; grass, forage at 9.0 ppm; and 

grass, hay at 25.0 ppm. The tolerance expression under 40 CFR §180.454 is correct and reflects 

measurement and compliance of nicosulfuron residues. Since the Section 18 tolerances in 

§180.454 (b) have expired, HED recommends they be revoked. Compliance with the tolerance 

levels is to be determined by measuring only nicosulfuron. A new use has been proposed on 

sorghum (78 FR 43115, 7/19/2013) and HED has completed a risk assessment for that use (K. 

Rury, D408756, 06/26/2014); however the use has not been registered as of the completion of 

the current document. Tolerances are recommended for residues in sorghum grain at 0.8 ppm, 

sorghum forage at 0.3, and sorghum stover at 0.05 ppm. An analytical reference standard for 

nicosulfuron with an expiration date of 09/03/2018 is available at EPA’s National Pesticide 

Standards Repository (e-mail dated 05/11/2015 from Theresa Cole, Analytical Chemistry 

Branch/Biological and Economic Analysis Division). 

At this time, there are no Codex maximum residue limits (MRLs) established for residues of 

nicosulfuron. Canadian MRLs are established on blueberries and corn and are expressed in 

terms of nicosulfuron. US tolerances and Canadian MRLs are harmonized for field corn grain. 

Canada does not establish tolerances on livestock feed items, whereas the US does. Canada has 

not established tolerances for residues on livestock commodities. Refer to Appendix E. 

2.2 Use Profile & Anticipated Exposure Pathways 

Nicosulfuron is formulated as dry flowable (DF) and liquid formulations. Currently registered 

labels include five technical/manufacturing use product labels and 27 end use product labels. In 

general, nicosulfuron may be applied once or twice per year or growing season. Registered use 

sites include corn (field, pop, seed, and sweet), herbicide-resistant sorghum, non-crop areas, and 

bermudagrass (including rights of way, non-crop areas, airports, landing fields, 

grass/forage/fodder/hay, industrial areas, marshes bogs, non-agricultural rights of way, sewage 

disposal areas). Nicosulfuron may be applied using groundboom, aerial, and handheld 
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 4 of 32

application equipment; application via chemigation is prohibited on the registered labels. All the 

registered labels require occupational handlers to wear long-sleeved shirts, long pants, shoes, and 

socks. Some labels require the addition of chemical resistant gloves, waterproof gloves, aprons, 

coveralls, or dust mist respirators. The restricted entry intervals (REIs) range from 4 hours to 24 

hours on the registered nicosulfuron labels; labels with REIs greater than 4 hours and that require 

additional PPE beyond baseline attire and chemical resistant gloves are all products coformulated with other pesticide active ingredients. 

Individuals may be exposed to nicosulfuron via their diet (food and drinking water). There are 

no registered uses for nicosulfuron that will result in direct non-dietary (i.e., residential) 

exposures. However, there is the potential for indirect non-dietary exposure (incidental oral and 

dermal) to nicosulfuron related to spray drift. Agricultural workers may be exposed (dermal and 

inhalation) to nicosulfuron during mixing, loading, and/or applying the herbicide as well as during 

post-application activities. Exposure to nicosulfuron is expected to be short- and intermediate-term 

for occupational handlers and post-application workers. However, since the toxicity POD is the 

same for both durations, the handler and post-application assessment is protective of both 

durations. Exposure to nicosulfuron via spray drift is expected to be short-term only. 

Table 2.1. Summary of Directions for Use of Nicosulfuron.

Applic. 

Timing, 

Type, and 

Equip.

Formula

tion

[EPA 

Reg. 

No.]

Max. 

Applic. 

Rate (lb 

ai/A)

Max. No. 

Applic. 

per 

Season/

Year

Max. 

Seasonal 

Applic. 

Rate (lb 

ai/A)

PHI

(Days) Use Directions and Limitations

Corn (Field, Sweet, Seed, and Pop)

Postemergence; 

Groundboom, 

Aerial1

DF 0.062 2 0.062

30-85

Application may be applied when corn is up 

to 20 inches tall or that is exhibiting up to and 

including 6 leaf collars (V6). Best results are 

obtained when applications are made to young 

actively growing weeds. Use of a spray 

adjuvant is required or a combination adjuvant 

containing NIS, COC, MSO4and/or 

ammonium nitrogen fertilizer.

Liquid 0.063 2 0.063

Bermudagrass2

Postemergence; 

Ground boom, 

Aerial, 

Handheld1

DF

0.049 

(broadcast)

0.053 lb 

ai/A or 

0.025 

oz/gal 

(spot)

2 0.088 0

5

Application is to be made to Bermuda grass 

that has been established for at least one 

growing season, when broadleaf weeds are 

<4” and grass weeds are <2” tall or in 

diameter. Use of a spray adjuvant is required 

or a combination adjuvant containing NIS, 

COC4, and/or ammonium sulfate or 

urea/ammonium nitrate fertilizer.

Switchgrass Grown in Tennessee

Postemergence; 

Ground boom, 

Aerial1

DF 0.035 2

0.070

(implied)

0.088

(general 

restriction)

0

5

Application is to be made after the 

switchgrass has reached the 2-leaf stage, when 

weeds are young and actively growing. Use 

of an NIS is required.

Herbicide-Resistant Sorghum

Postemergence;

DF 0.062 2 0.084 Grain 

and 

Application is to be made to emerged 

sorghum that is up to 20 inches tall. 

Applications made to 4-20 inch tall sorghum 
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 5 of 32

Table 2.1. Summary of Directions for Use of Nicosulfuron.

Applic. 

Timing, 

Type, and 

Equip.

Formula

tion

[EPA 

Reg. 

No.]

Max. 

Applic. 

Rate (lb 

ai/A)

Max. No. 

Applic. 

per 

Season/

Year

Max. 

Seasonal 

Applic. 

Rate (lb 

ai/A)

PHI

(Days) Use Directions and Limitations

Groundboom, 

Aerial1

stover69

Forage

-48

(V3-V7 stage) are recommended for best 

weed control and crop tolerance. Apply to 

young actively growing weeds. Use of a spray 

adjuvant is required or a combination adjuvant 

containing NIS, COC, MSO4and/or 

ammonium nitrogen fertilizer.

Non-Crop Areas3

Groundboom, 

Aerial, 

Handheld1

DF

0.07 lb 

ai/A

0.00082 

lb ai/gal

2 0.14 N/A

1. Chemigation is not permitted on the registered labels.

2. Registered Bermudagrass use sites include: rights of way, non-crop areas, airports, landing fields, grass/forage/fodder/hay, 

industrial areas, marshes bogs, non-agricultural rights of way, and sewage disposal areas.

3. Non-crop areas include: Fencerows, etc. May also be used selectively in established bermudagrass rough turf to control 

weeds) Industrial area/turf only.

4. NIS = Nonionic Surfactant. COC = Crop Oil Concentrate. MSO = Methylated Seed oil

5. The label states that there are no grazing or haying restrictions.

2.3 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in the 

preliminary human health risk assessment for nicosulfuron, in accordance with U.S. Executive 

Order 12898, Federal Actions to Address Environmental Justice in Minority Populations and 

Low-Income Populations1. As a part of every pesticide risk assessment, OPP considers a large 

variety of consumer subgroups according to well-established procedures. In line with OPP 

policy, HED estimates risks to population subgroups from pesticide exposures that are based on 

patterns of that subgroup’s food and water consumption, and activities in and around the home 

that involve pesticide use in a residential setting. Extensive data on food consumption patterns 

are compiled by the USDA under the National Health and Nutrition Examination Surveys/What 

We Eat in America (NHANES/WWEIA) and are used in pesticide risk assessments for all 

registered food uses of a pesticide. These data are analyzed and categorized by subgroups based 

on age and ethnic group. Additionally, OPP is able to assess dietary exposure to smaller, 

specialized subgroups and exposure assessments are performed when conditions or 

circumstances warrant. Whenever appropriate, non-dietary exposures based on home use of 

pesticide products and associated risks for adult applicators and for toddlers, youths, and adults 

entering or playing on treated areas post-application are evaluated. Further considerations are 

currently in development as OPP has committed resources and expertise to the development of 

specialized software and models that consider exposure to bystanders and farm workers as well 

as lifestyle and traditional dietary patterns among specific subgroups. 

 

1 http://epa.gov/compliance/ej/resources/policy/exec_order_12898.pdf
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 6 of 32

3.0 Hazard Characterization

No new toxicity and/or metabolism data have been received since the last risk assessment. This 

assessment is a summary of prior assessments (K. Rury, D408756, 06/26/2014).

3.1 Summary of Toxicological Effects

Nicosulfuron inhibits the action of the plant enzyme acetolactate synthase (ALS)/acetohydroxy 

acid synthase (AHAS), leading to the disruption of cell division and elongation in the plant. 

ALS is not found in humans or other mammals. A gene coding for a similar protein (ilvB-like, 

ILVBL, also known as bacterial acetolactate synthase-like) has been found in humans, however 

the protein or function associated with this gene is not known. Therefore, the herbicidal mode of 

action of nicosulfuron is not relevant to mammals.

Upon oral administration to rats, nicosulfuron appears to be incompletely absorbed, and is 

mostly excreted unchanged in feces (80-95%) and urine (9-20%) with trace residues in tissues. 

Minor metabolites of hydrolytic and oxidative metabolism were identified. A dermal absorption 

study is not available, therefore a default 100% dermal absorption factor is used in this risk 

assessment.

In repeated dose studies by the oral route, nicosulfuron is minimally toxic, and rodents are 

particularly insensitive to its effects. Dietary administration at or near the limit dose (1000 

mg/kg/day) to rats for 24 months or to mice for 18 months did not produce adverse effects. 

Dietary administration to dogs for one year produced mild effects (increase in the relative liver 

and kidney weights of males) at the highest doses tested (500 mg/kg/day). 

Nicosulfuron showed no developmental effects in rats, but produced abortions in rabbits at doses 

that also showed maternal toxicity. Decreased litter size was observed in a rat reproductive study 

from dams feed nicosulfuron levels above the limit dose. There are no indications of neurotoxic 

or immunotoxic effects elicited by nicosulfuron in animal studies. Nicosulfuron is not likely to 

be carcinogenic based on studies in the rat and mouse and lack of in vitro and in vivo mutagenic 

effects. 

3.2 Safety Factor for Infants and Children (FQPA Safety Factor)

The toxicity database of nicosulfuron is complete and adequate to assess the qualitative or 

quantitative susceptibility in the young. There is no evidence of increased qualitative or 

quantitative susceptibility in the young, there is no evidence of neurotoxicity, and exposure 

estimates are unlikely to underestimate risk; therefore, the FQPA Safety Factor (10X) is reduced 

to 1X.

3.3 Toxicity Endpoint and Point of Departure Selections

There have been no changes to the prior dose-response assessment or cancer classification (K. 

Rury, D408756, 06/26/2014). The toxicity endpoints and points of departures are presented in 

Table 3.1, and a summary of the toxicological database used as the rationale for the selections is 

presented in Appendix A.

There have been no changes to the prior recommendations for combining routes of exposure. 

There are no registered residential uses proposed of nicosulfuron. For occupational uses of 

nicosulfuron, because the dermal and inhalation POD are the same, dermal and inhalation risk 
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 7 of 32

estimates have been combined. 

Table 3.1 Summary of Toxicological Doses and Endpoints for Nicosulfuron for Use in Dietary,

Non-Occupational, and Occupational 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

Acute Dietary (General 

Population, including 

Infants and Children and 

Females 13-49 years of 

age)

No hazard was identified from appropriate oral toxicity studies including 

developmental toxicity studies in rats and rabbits. 

Chronic Dietary (All 

Populations)

NOAEL= 

125

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

DAF = 100%

cRfD = 1.25

mg/kg/day

cPAD = 1.25

mg/kg/day

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 (LOAEL = 500 

mg/kg/day, NOAEL = 100 

mg/kg/day).

Incidental oral (Short- and 

Intermediate-Term)

Residential LOC 

for MOE = 100

Dermal Exposure (All 

durations) Occupational LOC 

for MOE = 100 Inhalation Exposure (Shortand Intermediate-Term)

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. 

UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest 

observed adverse effect level, cPAD = chronic population adjusted dose, cRfD = chronic reference dose, MOE = margin of 

exposure, LOC = level of concern, NA = Not Applicable, FQPA = Food Quality Protection Act, DAF = dermal absorption factor.

3.4 Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic, and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different taxonomic 

groups. As part of its most recent registration decision for nicosulfuron, EPA reviewed these data 

and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing 

hazard database. However, as required by FFDCA section 408(p), nicosulfuron is subject to the 

endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 8 of 32

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of 

chemicals identified for EDSP screening was published on June 14, 20132and includes some 

pesticides scheduled for Registration Review and chemicals found in water. Neither of these 

lists should be construed as a list of known or likely endocrine disruptors. 

For further information on the status of the EDSP, the policies and procedures, the lists of 

chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website.3

4.0 Residue Chemistry

The nature of the residue in corn and canola metabolism studies is adequate to satisfy data 

requirements for the registered crops. The nature of the residue in livestock is adequately 

understood based on metabolism studies on dairy cows and laying hens. HED has determined 

that the residue of concern (ROC) for tolerance enforcement and risk assessment is the parent 

compound (nicosulfuron) for plants and livestock. The need for additional plant metabolism 

studies to support future uses will be decided on a case-by-case basis (D302694, D. Hrdy, 

11/30/2004). 

Adequate high performance liquid chromatography methods with tandem mass spectroscopic 

detection (HPLC/MS/MS) are available for tolerance enforcement of grass and sorghum 

commodities (DuPont-17928 and DuPont-32277) (D360897, W. Drew, 11/6/2009 and D417854, 

M. Negussie, 03/17/2014). An HPLC/UV (ultraviolet) method is available for tolerance 

enforcement of corn commodities (D302694, D. Hrdy, 11/30/2004). The methods have been 

adequately validated for the determination of residues of nicosulfuron in plants.

The LC/MS/MS method determines residues of parent and metabolite 2-aminosulfonyl]-N,Ndimethyl-3-pyridinecarboxamide (IN-V9367) separately. The method limit of quantitation 

(LOQ) is 0.010 ppm for each analyte in all matrices. 

Multiresidue methods testing data were previously submitted for nicosulfuron, which indicated 

 

2 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals.

3 http://www.epa.gov/endo/
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 9 of 32

that the methods are not applicable to nicosulfuron determination. 

The structure and the physical/chemical properties are summarized in Appendix C. 

5.0 Dietary Risk Assessment

For this DRA, an updated dietary exposure assessment has been completed for nicosulfuron to 

incorporate updated food consumption data and drinking water modeling estimates. The use 

pattern, PODs, and residue inputs to the dietary assessment have not changed since the previous 

assessment.

5.1 Water Residue Profile 

Screening ground water-sourced drinking water exposure estimates were generated with the 

Pesticide Root Zone Model for Ground Water (PRZM-GW; v.1.07) for use in the SU dietary risk 

assessments. Rather than produce chemical-specific estimated drinking water concentrations 

(EDWCs) following the usual assessment procedures, the Environmental Fate and Effects 

Division (EFED) provided coarse-screen estimates that should exceed upper-bound chemicalspecific EDWCs for any SU. This was achieved by using model inputs that represent the use 

pattern of highest exposure from any SU, the highest soil mobility of any SU residue of concern, 

and persistence to any route of degradation over time. The resulting highest coarse-screen 

EDWCs from PRZM-GW can be used as conservative screening-level estimates of exposure and 

are summarized in Table 5.1 (G. Orrick, D427429, 8/12/2015). 

The chronic dietary assessments for nicosulfuron used the post-breakthrough mean value of 492 

μg/L (0.492 ppm) from the North Carolina cotton scenario. 

Table 5.1. PRZM-GW Coarse-Screen EDWCs for Sulfonylureas1.

Modeled Scenario Kd or KOC

Initial Application 

Dates (days postemergence)

Max. Daily Conc. 

(μg/L)

Mean 

Breakthrough 

Time (yrs)

Postbreakthrough 

Mean (μg/L)

WI corn

Kd 7 449 11.5 415

KOC 7 504 6.9 425

DMV corn

Kd 7 489 5.3 369

KOC 7 560 3.3 378

FL citrus

Kd 7 429 3.2 351

KOC 7 467 2.3 349

FL potato

Kd 7 375 2.6 272

KOC 7 407 2.2 275

GA peanut

Kd 7 197 5.2 156

KOC 7 206 3.9 158

NC cotton

Kd 7 640 8.7 492

Kd 37 641 8.7 491

Kd 67 637 8.7 490

KOC 7 742 5.7 484

KOC 37 751 5.7 483

KOC 67 744 5.7 482

1 Maximum values are bolded and were used in the chronic dietary assessment.
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 10 of 32

5.2 Dietary (Food + Water) Exposure Assessment

HED has conducted a screening-level chronic dietary risk assessment for nicosulfuron using 

tolerance-level residues in foods and a sulfonylurea-class-wide screening-level estimate of 

residues in drinking water (G. Orrick, D427429, 8/12/2015). Exposure and risk estimates were 

obtained from the Dietary Exposure Evaluation Model using the Food Commodity Intake 

Database (DEEM-FCID; version 3.16). The model uses food consumption data from the 2003-

2008 NHANES/WWEIA (National Health and Nutrition Examination Survey, What We Eat in 

America) database, coupled with recipe files and residues in foods, to derive estimates of dietary 

exposure and risk. Generally, HED is concerned when chronic dietary exposure estimates 

exceed 100% of the chronic population adjusted dose (cPAD). In the case of nicosulfuron, the 

dietary risk estimates (Table 5.2) range from <1.0 to 2.2% of the cPAD and are below HED’s 

level of concern. Because of the very conservative assumptions used in the analysis (tolerancelevel residues, 100% crop treated, default processing factors, upper-bound modeled drinking 

water estimates), actual exposure and risk are expected to be much lower than those shown in 

Table 5.2. The listings of inputs and outputs to the assessment are included in Appendix B. 

HED did not conduct an acute dietary exposure/risk assessment because an acute dietary POD 

was not selected for nicosulfuron. Nicosulfuron is considered “not likely to be carcinogenic to 

humans”; therefore, cancer risk is not a concern. 

Table 5.2. Summary of dietary exposure and risk estimates for Nicosulfuron.

Population Group

Chronic Estimates

Exposure, mg/kg bw/day Risk, % cPAD

General US Population 0.010525 <1.0

All Infants (< 1 year old) 0.026963 2.2

Children 1-2 years old 0.015634 1.3

Children 3-5 years old 0.013125 1.0

Children 6-12 years old 0.009434 <1.0

Youth 13-19 years old 0.007753 <1.0

Adults 20-49 years old 0.010451 <1.0

Adults 50-99 years old 0.010280 <1.0

Female 13-49 years old 0.010407 <1.0

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are no registered residential uses or occupational uses resulting in residential exposure to 

nicosulfuron. Therefore, a quantitative residential exposure assessment was not performed. 

6.1 Spray Drift 

Off-target movement of pesticides can occur via many types of pathways and it is governed by a 

variety of factors. Sprays that are released and do not deposit in the application area end up offtarget and can lead to exposures to those it may directly contact. They can also deposit on 

surfaces where contact with residues can eventually lead to indirect exposures (e.g., children 
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 11 of 32

playing on lawns where residues have deposited next to treated fields). The potential risk 

estimates from these residues can be calculated using drift modeling onto 50 feet wide lawns 

coupled with methods employed for residential risk assessments for turf products.

The approach to be used for quantitatively incorporating spray drift into risk assessment is based 

on a premise of compliant applications which, by definition, should not result in direct exposures 

to individuals because of existing label language and other regulatory requirements intended to 

prevent them. 4 

Direct exposures would include inhalation of the spray plume or being sprayed directly. Rather, 

the exposures addressed here are thought to occur indirectly through contact with impacted areas, 

such as residential lawns, when compliant applications are conducted. Given this premise, 

exposures for children (1 to 2 years old) and adults who have contact with turf where residues 

are assumed to have deposited via spray drift thus resulting in an indirect exposure are the focus 

of this analysis analogous to how exposures to turf products are considered in risk assessment. 

In order to evaluate the drift potential and associated risks, an approach based on drift modeling 

coupled with techniques used to evaluate residential uses of pesticides was utilized. Essentially, a 

residential turf assessment based on exposure to deposited residues has been completed to 

address drift from the agricultural applications of nicosulfuron. In the spray drift scenario, the 

deposited residue value was determined based on the amount of spray drift that may occur at 

varying distances from the edge of the treated field using the AgDrift (v2.1.1) model and the 

Residential Exposure Assessment Standard Operating Procedures Addenda 1: Consideration of 

Spray Drift Policy. Once the deposited residue values were determined, the remainder of the 

spray drift assessment was based on the algorithms and input values specified in the recently 

revised (2012) Standard Operating Procedures For Residential Risk Assessment (SOPs). 

A screening approach was developed based on the use of the AgDrift model in situations where 

specific label guidance that defines application parameters is not available.2 AgDrift is 

appropriate for use only when applications are made by aircraft, airblast orchard sprayers, and 

groundboom sprayers. When AgDrift was developed, a series of screening values (i.e., the Tier 

1 option) were incorporated into the model and represent each equipment type and use under 

varied conditions. The screening options specifically recommended in this methodology were 

selected because they are plausible and represent a reasonable upper bound level of drift for 

common application methods in agriculture. These screening options are consistent with how 

spray drift is considered in a number of ecological risk assessments and in the process used to 

develop drinking water concentrations used for risk assessment. In all cases, each scenario is to 

be evaluated unless it is not plausible based on the anticipated use pattern (e.g., herbicides are 

not typically applied to tree canopies) or specific label prohibitions (e.g., aerial applications are 

not allowed). Section 6.1.1 provides the screening level drift related risk estimates. 

In many cases, risks are of concern when the screening level estimates for spray drift are used as 

the basis for the analysis. In order to account for this issue and to provide additional risk 

management options additional spray drift deposition fractions were also considered. These drift 

 

4 This approach is consistent with the requirements of the EPA’s Worker Protection Standard.

2 http://www.epa.gov/pesticides/science/models_pg.htm 
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 12 of 32

estimates represent plausible options for pesticide labels. 

6.1.1 Combined Risk Estimates From Lawn Deposition Adjacent to Applications

The spray drift risk estimates are based on an estimated deposited residue concentration as a 

result of the screening level agricultural application scenarios. Nicosulfuron is used on corn, 

sorghum, bermudagrass, and non-crop areas and can be applied via aerial, groundboom, and 

handheld equipment. The recommended drift scenario screening level options are listed below: 

 Groundboom applications are based on the AgDrift option for high boom height and 

using very fine to fine spray type using the 90th percentile results. 

 Aerial applications are based on the use of AgDrift Tier 1 aerial option for a fine to 

medium spray type and a series of other parameters which will be described in more 

detail below (e.g., wind vector assumed to be 10 mph in a downwind direction for entire 

application/drift event).1

Dermal and incidental oral risk estimates were combined because the toxicity endpoint for each 

route of exposure is based on increased relative liver and kidney weights from the same study. 

The total applicable Level of Concern is 100; therefore MOEs < 100 are of concern. Adult 

dermal and children’s (1 to <2 year old) dermal and incidental oral risk estimates from indirect 

exposure to nicosulfuron related to spray drift result in no risks of concern at field edge. 

Table 6.1.1. Adult Dermal Risk Estimates (MOEs) Related to Spray Drift Exposure to 

Nicosulfuron from the Registered Agricultural Uses. 

Application 

Type

Spray Type/Nozzle 

Configuration

Appl. Rate 

(lb ai/A)

TTR 

(μg/cm2)

2

At Edge 

(LOC = 100)

Corn1

Aerial Fine to Medium 0.063 0.0070 21,000

Groundboom High Boom Very fine to Fine 28,000

Bermudagrass1

Aerial Fine to Medium 0.049 0.00544 26,000

Groundboom High Boom Very fine to Fine 36,000

Non-Crop Areas1

Aerial Fine to Medium 0.07 0.0078 19,000

Groundboom High Boom Very fine to Fine 25,000

Sorghum1

Aerial Fine to Medium 0.062 0.0069 21,000

Groundboom High Boom Very fine to Fine 29,000

1 Assessed using the highest registered application rates.

2 HED’s default assumption that 10% 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.

 

1 AgDrift allows for consideration of even finer spray patterns characterized as very fine to fine. However, this 

spray pattern was not selected as the common screening basis since it is used less commonly for most agriculture. 
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 13 of 32

Table 6.1.2. Combined Dermal and Hand-to-Mouth Exposure for Children 1 to <2 Years Old 

Risk Estimates (MOEs) Related to Spray Drift Exposure to Nicosulfuron from the Registered 

Agricultural Uses.

Application 

Type

Spray Type/Nozzle 

Configuration

Appl. Rate 

(lb ai/A)

TTR 

(μg/cm2)

2

At Edge 

(LOC = 100)

Corn1

Aerial Fine to Medium 0.063 0.0070 10,000

Groundboom High Boom Very fine to Fine 14,000

Bermudagrass1

Aerial Fine to Medium 0.049 0.00544 13,000

Groundboom High Boom Very fine to Fine 18,000

Non-Crop Areas1

Aerial Fine to Medium 0.07 0.0078 9,200

Groundboom High Boom Very fine to Fine 13,000

Sorghum1

Aerial Fine to Medium 0.062 0.0069 10,000

Groundboom High Boom Very fine to Fine 14,000

1 Assessed using the highest registered application rates. 

2 HED’s default assumption that 10% 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.

6.2 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.1 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 nicosulfuron.

7.0 Aggregate Exposure/Risk Characterization

The Food Quality Protection Act of 1996 directs EPA to assess aggregate exposure to pesticide 

chemical residues, including all anticipated dietary exposures and all other exposures for which 

there is reliable information. In the case of nicosulfuron, aggregate exposure and risk estimates 

are equivalent to the dietary exposure and risk estimates in Section 5.2 and are not of concern. 

There are no registered uses for nicosulfuron that will result in direct non-dietary (i.e., 

residential) exposures. However, there is the potential for indirect non-dietary exposure 

(incidental oral and dermal) to nicosulfuron related to spray drift. Residential exposures 

resulting from spray drift are not included in the aggregate assessment because the likelihood of 

 

1 Available at: http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219.
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 14 of 32

co-occurrence with dietary (food + drinking water) exposures is very low. 

8.0 Cumulative Exposure/Risk Characterization

In 2015, EPA’s Office of Pesticide Programs released a guidance document entitled, Pesticide 

Cumulative Risk Assessment: Framework for Screening Analysis1. This document provides 

guidance on how to screen groups of pesticides for cumulative evaluation using a two-step 

approach beginning with the evaluation of available toxicological information and if necessary, 

followed by a risk-based screening approach. This framework supplements the existing 

guidance documents for establishing common mechanism groups (CMGs)2and conducting 

cumulative risk assessments (CRA)3. The Agency has utilized this framework to evaluate the 

SUs of which [chemical name] is a member (J. D’Agostino; D428798; 9/9/15). Although the 

SUs share some chemical and toxicological characteristics, the toxicological database does not 

support a testable hypothesis for a common mechanism of action. No further mechanistic data 

are required and no further cumulative evaluation is necessary.

9.0 Occupational Exposure/Risk Characterization

9.1 Occupational Handler Exposure

There is potential occupational handler dermal and inhalation exposure from the registered uses 

of nicosulfuron. The quantitative exposure/risk assessment developed for occupational handlers 

is based on the scenarios listed in Table 9.1. Dermal and inhalation exposures were combined in

this assessment, since the toxicological effects for these exposure routes were similar. Only 

short- and intermediate-term exposures are expected for nicosulfuron; and the PODs selected to 

evaluate dermal and inhalation exposures covers both durations. 

The standard body weight (80 kg) was used in this risk assessment since the endpoint selected 

was not developmental and/or based on fetal effects. Since no inhalation absorption data are 

available, toxicity by the inhalation route is considered to be equivalent to the estimated toxicity 

by the oral route of exposure.

All occupational handler scenarios for the registered uses resulted in MOEs greater than 100 at 

baseline level of risk mitigation (i.e., baseline attire with no gloves or respirator) or engineering 

control for aerial applications (i.e., enclosed cockpits) and, therefore, are not of concern. The 

lowest combined (dermal + inhalation) MOE of 500 is associated with mixing/loading/applying

a dry flowable formulation to industrial/commercial areas (non-crop areas). 

 

1 http://www.epa.gov/oppfead1/cb/csb_page/updates/2015/framework-for-screening-analysis.html

2 Guidance For Identifying Pesticide Chemicals and Other Substances that have a Common Mechanism of Toxicity 

(USEPA, 1999)

3 Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a Common Mechanism of Toxicity 

(USEPA, 2002)
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 15 of 32

Table 9.1. Occupational Handler Short- and Intermediate-Term Non-Cancer Exposure and Risk Estimates for Nicosulfuron. 

Exposure 

Scenario Crop or Target Level of Concern

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 Combined 

Baseline Baseline Dose 

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

Mixer/Loader

Mixing/Loading 

Dry Flowables for 

Aerial Application

Non-Crop Areas9

100

227 8.96

0.07 lb ai/A 350 A 0.0695 1,800 0.00275 45,000 1,700

Corn & Sorghum 0.62 lb ai/A 1200 A 0.211 590 0.00834 15,000 570

Mixing/Loading 

Dry Flowables for 

Groundboom 

Application

Non-Crop Areas9 0.07 lb ai/A 80 A 0.0159 7,900 0.000628 200,000 7,600

Corn & Sorghum 0.062 lb 

ai/A 200 A 0.0351 3,600 0.00139 90,000 3,500

Mixing/Loading 

Liquids for Aerial 

Application

Non-Crop Areas9

220 0.219

0.07 lb ai/A 350 A 0.0674 1,900 0.0000671 1,900,000 1,900

Corn 0.063 lb 

ai/A 1200 A 0.208 600 0.000208 600,000 600

Mixing/Loading 

Liquids for 

Groundboom 

Application

Corn 0.063 lb 

ai/A 200 A 0.0346 3,600 0.0000345 3,600,000 3,600

Applicator

Applying Sprays 

via Aerial 

Equipment

Non-Crop Areas9

100

2.08 0.0049

0.07 lb ai/A 350 A 0.000638 200,000 0.0000015 83,000,000 200,000

Corn & Sorghum 0.063 lb 

ai/A 1200 A 0.00196 64,000 0.00000463 27,000,000 64,000

Applying Sprays 

via Groundboom 

Equipment

Non-Crop Areas9

78.6 0.34 0.07 lb ai/A

80 A 0.0055 23,000 0.0000238 5,300,000 23,000

Corn & Sorghum 200 A 0.0124 10,000 0.0000535 2,300,000 10,000

Applying Sprays 

via Mechanically 

Pressurized 

Handgun

Non-Crop Areas9 1300 3.9 0.005 lb 

ai/gal 1000 gal 0.0813 1,500 0.000244 510,000 1,500

Flagger

Flagging for 

Aerial 

Application

Non-Crop Areas9

100 11 0.35

0.07 lb ai/A

350 A

0.00338 37,000 0.000107 1,200,000 36,000

Corn & Sorghum 0.063 lb 

ai/A 0.00304 41,000 0.0000965 1,300,000 40,000
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 16 of 32

Table 9.1. Occupational Handler Short- and Intermediate-Term Non-Cancer Exposure and Risk Estimates for Nicosulfuron. 

Exposure 

Scenario Crop or Target Level of Concern

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 Combined 

Baseline Baseline Dose 

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

Mixer/loader/Applicator

Mixing/Loading/

Applying Sprays 

via Backpack 

Sprayers

Non-Crop Areas9

(Rights-of-Way)

100

8260 2.58

0.005 lb 

ai/gal

40 gal

0.0206 6,100 0.00000645 19,000,000 6,100

Non-Crop Areas9

(Industrial/

Commercial Areas)

2510 30 0.00628 20,000 0.000075 1,700,000 20,000

Mixing/Loading/

Applying Sprays 

via Manually 

Pressurized 

Handwand

Non-Crop Areas9

(Industrial/

Commercial 

Areas)

100,000 30 0.25 500 0.000075 1,700,000 500

Mixing/Loading/

Applying Sprays 

via Mechanically 

Pressurized 

Handgun

Non-Crop Areas9

(Industrial/

Commercial 

Areas)

1,300 3.9 1000 gal 0.0813 1,500 0.000244 510,000 1,500

Non-Crop Areas9 1,300 3.9 0.0813 1,500 0.000244 510,000 1,500

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (02/01/2015); Level of mitigation: Baseline. Note that aerial applicators are assessed 

as enclosed cockpit and baseline represents engineering controls. 

2 Based on registered nicosulfuron labels.

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 (80 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 (80 kg).

7

Inhalation MOE = Inhalation NOAEL (125 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

8 Total MOE = NOAEL (mg/kg/day) ÷ Dermal Dose + Inhalation Dose.

9 Non-crop areas include bermudagrass for the purposes of the occupational assessment. Registered Bermudagrass and non-crop use sites include: fencerows, rights of way, noncrop areas, airports, landing fields, grass/forage/fodder/hay, industrial areas, marshes bogs, non-agricultural rights of way, and sewage disposal areas. Bermudagrass was also 

assessed using the “typical field crop”, “rights of way”, and “industrial/commercial” exposure inputs as surrogates to assess exposure. 

ai = active ingredient; A = acres; gal = gallons
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 17 of 32

9.2 Occupational Post-Application Exposure

Both short- and intermediate-term dermal and inhalation exposures are expected for occupational 

post-application workers following nicosulfuron application. 

Occupational Post-Application Inhalation Exposure

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 Post-application Dermal Exposure and Risk Estimates

The algorithms used to estimate non-cancer exposure and dose for occupational post-application 

workers can be found in the footnotes of Table 9.2. Only low crop heights were assessed 

because nicosulfuron is applied early in the crop growing season for corn and sorghum. Postapplication exposure is not expected to non-crop areas and bermudagrass. It is unlikely workers 

would have to re-enter treated areas following application to these areas. The highest registered 

application rate of the products registered on corn and sorghum was used as a conservative 

estimate of exposure (0.063 lb ai/A). The occupational post-application MOEs ranged from 

3,700 to 100,000 on day 0, and are not of concern. 

Since the highest estimated occupational post-application exposure using default dislodgeable 

foliar residue (DFR) values for nicosulfuron is minimal in comparison to the level of concern 

(i.e., the calculated MOE is greater than 2 times higher than the level of concern, MOE = 3,700

compared to the LOC of 100); EPA is waiving the 40 CFR DFR data requirement at this time for 

currently registered uses. In this instance, it is unlikely that chemical-specific DFR data would 

be needed to further refine exposure assessments or would add appreciably to our overall 

understanding of the availability of dislodgeable foliar pesticide residues for nicosulfuron. 

Table 9.2. Occupational Post-application Non-Cancer Dermal Exposure and Risk Estimates for 

Nicosulfuron.

Crop/Site Activities Transfer Coefficient 

(cm2/hr)

DFR1

(μg/cm2)

Dermal Dose

(mg/kg/day)2

MOE3

Short- and Intermediate-Term

Corn & Sorghum

Scouting 210

0.18

0.0037 34,000

Hand-Set 

Irrigation 1900 0.0336 3,700

Hand Weeding 70 0.00124 100,000

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/TTR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption (100%)]  BW (80 kg).

3 MOE = POD (125 mg/kg/day) / Daily Dermal Dose. 

Restricted Entry Interval

Based on the acute toxicity categories and post-application assessment for nicosulfuron, the 

Worker Protection Standard (WPS) Interim Restricted Entry Interval (REI) for nicosulfuron is 

12-hours. REIs may be further reduced if certain criteria are met in accordance with the 
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 18 of 32

Pesticide Registration (PR) Notice 95-3 [Reduction of WPS Interim REIs for Certain Low Risk 

Pesticides]11. In PR Notice 95-3, there are a set of criteria listed for the active ingredient that 

must be met for chemicals to be eligible for a reduced REI. These criteria include:

1. The active ingredient is in Toxicity category III or IV based upon data for acute dermal 

toxicity, acute inhalation toxicity, primary skin irritation, and primary eye irritation. 

Acute oral toxicity data were used if no acute dermal data were available. If EPA lacked 

data on primary skin irritation, acute inhalation, or primary eye irritation of the active 

ingredient, the Agency reviewed data on that end-point for similar active ingredients 

(analogs), and excluded such active ingredients from consideration for the reduced REI, 

if the analog is in Toxicity Category I or II for that endpoint.

2. The active ingredient is not a dermal sensitizer (or in the case of biochemical and 

microbial active ingredients, no known reports of hypersensitivity exist).

3. The active ingredient is not a cholinesterase inhibitor (NMethyl carbamate and 

Organophosphate) as these chemicals are known to cause large numbers of pesticide 

poisonings and have the potential for serious neurological effects.

4. No known reproductive, developmental, carcinogenic, or neurotoxic effects have been 

associated with the active ingredient. If active ingredients did not have data available for 

these chronic health effects, EPA considered data on appropriate chemical and biological 

analogs. Active ingredients that have been classified as carcinogenic in Category B 

(probable human carcinogen) or Category C with a potency factor, Q* (possible human 

carcinogen, for which quantification of potential risk is considered appropriate), or are 

scheduled for the Health Effects Division's Cancer Peer Review process, were omitted 

from consideration.

5. EPA does not possess incident information (illness or injury reports) that are ``definitely'' 

or ``probably'' related to post-application exposures to the active ingredient.

Upon review of the criteria for the active ingredient only, it appears that nicosulfuron is 

consistent with the criteria in PRN 95-3 that allow for a 4-hour REI. Note: The PR Notice also 

includes similar criteria for the end-use product. These criteria have not been evaluated by 

HED. Based solely on the active ingredient criteria, HED would recommend for reduction of the 

REI for nicosulfuron.

10.0 Public Health and Pesticide Epidemiology Data

Evaluation of the OPP Incident Data System (IDS) (S. Recore, D398572, 2/14/12; includes 

incidents from January 1, 2006 through December 14, 2011) indicated that no single chemical 

nicosulfuron incidents were identified in the United States. In the aggregate IDS (which reports 

incidents of multiple chemical exposures at the same time) there were 5 incidents reported for 

nicosulfuron. Because it falls within the categories reported as counts (which includes minor, 

unknown or no effects), there is no unique report that provides details about the incident and 

single chemical incidents are not distinguished from multiple chemical incidents. A high 

 

11 Available: http://www.epa.gov/PR_Notices/pr95-3.html
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 19 of 32

frequency of incidents indicates there is a high potential for exposure and vice versa. However 

for nicosulfuron, there appears to be a low potential for exposure. Nicosulfuron is not included 

in the Agricultural Health Study (AHS), and therefore, the AHS does not provide information for 

this report. There does not appear to be a concern at this time that would warrant further 

investigation. The Agency will continue to monitor the incident information. If a concern is 

triggered, additional analysis will be included in the risk assessment.

11.0 References

Federal Register Notices

Receipt of Several Pesticide Petitions Filed for Residues of Pesticide Chemicals in or on Various 

Commodities; Notice of filing of petitions and request for comment. 78 Federal Register 139 (19 

July 2013), pp. 43115-43118.

Memoranda Relevant to Registration Review of Nicosulfuron – Risk Assessments

Author Barcode Date Title

D. Hrdy D302694 11/30/2004 Nicosulfuron HED Chapter of the Reregistration Eligibility 

Decision Document (RED). 

A. Parmar D335236 10/18/2007 Nicosulfuron- Side-by-Side Field Trials on Corn using 

Suspension Concentrate and Water Dispersible Granule 

Formulations.

W. Cutchin D361732 7/14/2009 Nicosulfuron: Human Health Risk Assessment for Proposed 

Section 18 Use on Bermudagrass.

M. Doherty D360807 10/27/2009 Nicosulfuron. Human Health Risk Assessment for the Proposed 

Use on Grasses.

Memoranda Relevant to Registration Review of Nicosulfuron – Incident Reports

Author Barcode Date Title

S. Recore D398572 2/14/2012 Nicosulfuron: Review of Human Incidents

Memoranda Relevant to Registration Review of Nicosulfuron – Residue Chemistry

Author Barcode Date Title

J. Stokes D207115, 

D207117

N/A Nicosulfuron in/on Sweet Corn. Evaluation of Analytical 

Method and Residue Data.

J. Stokes D221715, 

D221718

6/9/1995 Nicosulfuron in/on Sweet Corn Amendments.

A. Parmar D338945, 

D342602

10/18/2007 Nicosulfuron: Section 3 Registration of Nicosulfuron 2L (EPA 

File Symbol: 67760-TU) for Use on Corn. Summary of 

Analytical Chemistry and Side-by-Side Residue Data.

A. Parmar D346994 5/13/2008 Nicosulfuron. Request for Waiver of Sorghum Metabolism 

Study, Poultry Metabolism Study and Poultry Feeding Study. 

W. Drew D360897 11/6/2009 Nicosulfuron: Petition Requesting Establishment of Permanent 

Tolerances (Associated with Section 3 Registration) for 

Residues Resulting from New Food/Feed Use of the Herbicide 

on Grasses. Summary of Analytical Chemistry and Residue 

Data.

M. Doherty D374717 3/2/2010 Nicosulfuron – Resolution of Analytical Method Deficiencies 
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 20 of 32

Noted in HED Review D360897.

M. Negussie D417854 03/17/2014 Nicosulfuron: Petition for the Establishment of Permanent 

Tolerances for Uses on Acetolactase Synthase (ALS) Tolerant 

Grain Sorghum. Summary of Analytical Chemistry and Residue 

Data.

M. Negussie D417840 03/17/2014 Nicosulfuron: Chronic Aggregate Dietary (Food plus Drinking 

Water) Exposure and Risk Assessments in Support of a Section 

3 Registration on Acetolactase Synthase (ALS) Tolerant Grain 

Sorghum.

G. Orrick, D427429, 8/12/2015 Drinking Water Exposure Assessment for the Registration 

Review of 22 Sulfonylurea Herbicides

Memoranda Relevant to Registration Review of Nicosulfuron – Other

Author Barcode Date Title

J. Van 

Alstine

TXR 

0050011

8/2/12 Nicosulfuron: Summary of Hazard and Science Policy Council 

(HASPOC) Meetings of March 29, 2012: Recommendations on 

the requirement of 90-day inhalation and 28-day dermal 

toxicity studies and neurotoxicity screening battery.
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 21 of 32

Appendix A. Toxicology Profile 

A.1 Toxicology Data Requirements

The requirements (40 CFR §158.340) for food uses of nicosulfuron are in the table below. Use of 

the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Study

Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

870.1200 Acute Dermal Toxicity..................................................

870.1300 Acute Inhalation Toxicity..............................................

870.2400 Acute Eye Irritation.......................................................

870.2500 Acute Dermal Irritation .................................................

870.2600 Skin Sensitization..........................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 90-Day Oral Toxicity in Rodents..................................

870.3150 90-Day Oral Toxicity in Nonrodents.............................

870.3200 21/28-Day Dermal Toxicity ..........................................

870.3250 90-Day Dermal Toxicity ...............................................

870.3465 90-Day Inhalation Toxicity ...........................................

yes

yes

yes

no

yes

yes

yes

waived 1

–

waived 1

870.3700a Prenatal Developmental Toxicity (rodent) ....................

870.3700b Prenatal Developmental Toxicity (nonrodent) ..............

870.3800 Reproduction and Fertility Effects ................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)..............................................

870.4100b Chronic Toxicity (nonrodent)........................................

870.4200a Carcinogenicity (rat)......................................................

870.4200b Carcinogenicity (mouse) ...............................................

870.4300 Combined Chronic Toxicity/Carcinogenicity ...............

yes

yes

yes

yes

no

2

yes

2

yes

yes

870.5100 Mutagenicity—Bacterial Reverse Mutation Test ..........

870.5300 Mutagenicity—Mammalian Cell Gene Mutation Test..

870.5385 Mutagenicity—Structural Chromosomal Aberrations...

870.5550 Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

yes

yes

870.6200a Acute Neurotoxicity Screening Battery (rat).................

870.6200b 90-Day Neurotoxicity Screening Battery (rat) ..............

870.6300 Developmental Neurotoxicity .......................................

yes

yes

no

yes

yes

–

870.7485 Metabolism and Pharmacokinetics................................

870.7600 Dermal Penetration........................................................

870.7800 Immunotoxicity .............................................................

yes

no

yes

yes

–

yes

1 The requirement for this study has been waived (J. Van Alstine; 8/2/12; TXR 0050011).

2 A chronic/oncogenicity study is available for the rat, thus separate chronic and oncogenicity are not necessary.
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 22 of 32

A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Profile of 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 an irritant IV

870.2600 Skin sensitization – guinea pig 41082604 Not a sensitizer NA

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Nicosulfuron

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

870.3100

90-Day Oral Toxicity in 

Rodents (rat)

41082607 (1988)

Acceptable/guideline

0, 300, 1500, 7500 or 

20,000 ppm

M: 0, 22, 107, 555, 1495; 

F: 0, 26, 133, 685, 1830

mg/kg/day

NOAEL = 1495/1830 mg/kg/day (M/F)

LOAEL = could not be established.

870.3150

90-Day Oral Toxicity in 

nonrodent (dog)

41082606 (1988)

Acceptable/guideline

0, 250, 5000, or 20,000 ppm

M: 0, 9, 172, 710; F: 0, 

9, 171, 683 mg/kg/day

NOAEL = 171 mg/kg/day (F)

LOAEL = 683 mg/kg/day based on decreased 

neutrophils (F only).

870.3700a

Prenatal developmental in 

rodent (rat)

41082608 (1988)

Acceptable/guideline

0, 200, 1000 , 2500 or 

6000 mg/kg/day

Maternal NOAEL = 6000 mg/kg/day

LOAEL = could not be established.

Developmental NOAEL = 6000 mg/kg/day

LOAEL = could not be established.

870.3700b

Prenatal developmental in 

nonrodent (rabbit)

41082609 (1988)

Acceptable/guideline

0, 100, 500, 1000 or 

2000 mg/kg/day

Maternal NOAEL = 100 mg/kg/day

LOAEL = 500 mg/kg/day based on increased incidence 

vaginal discharge, abortion, staining of hair in rectal and 

vaginal areas, as well as increased post-implantation loss 

and decreased body weight gain. Increased incidence of 

diarrhea at the next highest dose (1000 mg/kg/day).

Developmental NOAEL = 1000 mg/kg/day

LOAEL could not be determined.
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 23 of 32

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Nicosulfuron

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

870.3800

Reproduction and Fertility 

Effects (rat)

41360101 (1989)

Acceptable/guideline

0, 250, 5000 or 20,000 

ppm

M: 0, 15.6, 314, 1316; F: 

19.5, 380, 1588 

mg/kg/day 

Parental/Systemic NOAEL = 1203/1571 mg/kg/day (M/F)

LOAEL could not be established..

Reproductive NOAEL = 289/370 mg/kg/day (M/F)

LOAEL = 1203/1571 mg/kg/day (M/F) based on 

decrease litter size from F1 dams.

Offspring NOAEL = 1203/1571 mg/kg/day (M/F)

LOAEL could not be established.

870.4100b

Chronic toxicity (dog)

41360102 (1989)

Acceptable/guideline

0, 250, 5000 or 20,000 ppm

0, 6.25, 125, 500 mg/kg/day

NOAEL = 125 mg/kg/day

LOAEL = 500 mg/kg/day based on increased relative 

liver and kidney weights in males.

870.4200b

Carcinogenicity (mouse)

41360103 (1989)

Acceptable/guideline

0, 25, 250, 2500 or 7500 ppm 

M: 3, 31, 314, 953; F: 4, 

43, 420, 1260 mg/kg/day

NOAEL = 953/1260 mg/kg/day (M/F)

LOAEL could not be established.

No evidence of carcinogenicity.

870.4300

Combined Chronic 

Toxicity/Carcinogenicity 

(rat)

41360104 (1989)

Acceptable/guideline

0, 50, 1500, 7500 or 

20,000 ppm

M: 2, 58, 289, 786; F: 3, 

77, 382, 1098 mg/kg/day

NOAEL = 786/1098 mg/kg/day (M/F)

LOAEL could not be established.

No evidence of carcinogenicity.

870.5100

Bacterial Reverse Mutation

Test (Salmonella 

typhimurium)

41082612, 41360124 

(1988)

Acceptable/guideline

0.02 -10 μg/plate 

(not all strains tested at 

the same concentrations)

Negative in strains TA97A, TA98, TA100 and TA1535 

at doses reaching cytotoxic levels in the presence or 

absence of metabolic activation.

870.5300 

In vitro Mammalian Cell 

Gene Mutation Test

(Chinese Hamster Ovary 

(CHO) cells)

41082614, 41360123 

(1988)

Acceptable/guideline

4, 20, 40, 200 or 465 

μg/mL

Negative at doses reaching the limit of solubility in the 

presence or absence of metabolic activation.

870.5375 

In vitro Mammalian 

Chromosome Aberration 

Test (human lymphocytes)

41082615, 41368001 

(1988)

Acceptable/guideline

0, 200, 400 or 470 μg/mL

Negative at doses reaching the limit of solubility in the 

presence or absence of metabolic activation.
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 24 of 32

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Nicosulfuron

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

870.5385

Mammalian Bone Marrow 

Chromosome Aberration 

Assay (mouse)

41082616, 41360126 

(1988) 

Acceptable/guideline 

0, 500, 2500 or 5000 mg/kg

Negative for induction of chromosome aberrations in 

the bone marrow cells of male or female mice at 24, 48 

or 72 hrs post-exposure. 

870.5550 

Unscheduled DNA 

Synthesis in Mammalian 

Cells in Culture (rat 

hepatocytes)

41082613, 41360125 

(1998)

Acceptable/guideline

0.04, 0.4, 1.2, 4.1, 12, 41, 

122, 409 or 470 μg/mL

Negative for DNA damage or inducible repair in the rat 

hepatocyte.

870.6200a

Acute Neurotoxicity 

Screening Battery (rat)

48790905 (2011)

Acceptable/guideline 

0, 200, 1000, or 2000 mg/kg

NOAEL = 2000 mg/kg/day

LOAEL = could not be established.

870.6200b

Subchronic Neurotoxicity 

Screening Battery (rat)

48790903 (2011)

Acceptable/guideline 

0, 2500, 7500 or 18000 ppm

M: 0, 145, 449 or 1101; 

F: 0, 181, 532 or 1295 

mg/kg/day

NOAEL = 1101/1295 mg/kg/day (M/F)

LOAEL = could not be established.

870.7485

Metabolism and 

Pharmacokinetics (rat)

41082617 (1988)

Acceptable/guideline

Single dose oral: 10 or 

1000 mg/kg

Single dose iv: 10 mg/kg

Repeated dose oral: 10 

mg/kg/day for 14 days

Most of a single oral dose was excreted unchanged within 

24 hours and 98-109% within 4 days; the oral half-life was 

12-24 hours. 80-95% dose was eliminated in feces, 9-20% 

in urine and <0.01% in exhaled air. A slightly greater 

percent of the oral dose was detected in feces of high dose 

than low dose animals. After iv administration, 76-80% 

dose was eliminated in urine and 27-30% in the feces; the iv 

half-life was < 12 hours. Residues in tissues were 0.05-

0.5% dose; highest levels detected in the liver and kidneys. 

The major excretion product was unchanged parent 

compound. Pyridinesulfonamide was detected in urine (1.1-

5.7% dose). Pyridine acid sulfonamide was tentatively 

identified as a minor metabolite in the feces of orally dosed 

rats and urine of iv dosed rats. These metabolites represent 

hydrolytic cleavage/oxidation of the parent molecule. No 

differences were observed between sexes.

870.7800

Immunotoxicity (female 

mice)

48790904 (2011)

Acceptable/guideline

0, 300, 900, 1800 or 

7000 ppm

0, 60, 181, 333 or 1207 

mg/kg/day

NOAEL = 1207 mg/kg/day

LOAEL = could not be established.

M = males, F = females, PND = post natal day
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 25 of 32

Appendix B. Dietary Exposure/Risk Modeling Input and Output

U.S. EPA Ver. 3.16, 03-08-d

DEEM-FCID Chronic analysis for NICOSULFURON

Residue file: C:\Documents and Settings\MNEGUSSI\My Documents\DEEM Version 

3.16\Nicosulfuron\Chronic_Nicosulfuron2015PRA.R08

 Adjust. #2 NOT used

Analysis Date 05-12-2015 Residue file dated: 05-12-2015/09:33:56

Reference dose (RfD) = 1.25 mg/kg bw/day

Comment:Scoping-PRA EDWC-SU Coarse Screen Estimate

----------------------------------------------------------------------------------

Food Crop Residue Adj.Factors

EPA Code Grp Food Name (ppm) #1 #2 

---------- ---- ------------------------------- ---------- ------ ------

3100044000 31 Beef, meat 0.010000 1.000 1.000 

3100044001 31 Beef, meat-babyfood 0.010000 1.000 1.000 

3100045000 31 Beef, meat, dried 0.010000 1.920 1.000 

3100046000 31 Beef, meat byproducts 0.050000 1.000 1.000 

3100046001 31 Beef, meat byproducts-babyfood 0.050000 1.000 1.000 

3100047000 31 Beef, fat 0.010000 1.000 1.000 

3100047001 31 Beef, fat-babyfood 0.010000 1.000 1.000 

3100048000 31 Beef, kidney 0.050000 1.000 1.000 

3100049000 31 Beef, liver 0.050000 1.000 1.000 

3100049001 31 Beef, liver-babyfood 0.050000 1.000 1.000 

1500120000 15 Corn, field, flour 0.100000 1.000 1.000 

1500120001 15 Corn, field, flour-babyfood 0.100000 1.000 1.000 

1500121000 15 Corn, field, meal 0.100000 1.000 1.000 

1500121001 15 Corn, field, meal-babyfood 0.100000 1.000 1.000 

1500122000 15 Corn, field, bran 0.100000 1.000 1.000 

1500123000 15 Corn, field, starch 0.100000 1.000 1.000 

1500123001 15 Corn, field, starch-babyfood 0.100000 1.000 1.000 

1500124000 15 Corn, field, syrup 0.100000 1.000 1.000 

1500124001 15 Corn, field, syrup-babyfood 0.100000 1.000 1.000 

1500125000 15 Corn, field, oil 0.100000 1.000 1.000 

1500125001 15 Corn, field, oil-babyfood 0.100000 1.000 1.000 

1500126000 15 Corn, pop 0.100000 1.000 1.000 

1500127000 15 Corn, sweet 0.100000 1.000 1.000 

1500127001 15 Corn, sweet-babyfood 0.100000 1.000 1.000 

3200169000 32 Goat, meat 0.010000 1.000 1.000 

3200170000 32 Goat, meat byproducts 0.050000 1.000 1.000 
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 26 of 32

3200171000 32 Goat, fat 0.010000 1.000 1.000 

3200172000 32 Goat, kidney 0.050000 1.000 1.000 

3200173000 32 Goat, liver 0.050000 1.000 1.000 

3300189000 33 Horse, meat 0.010000 1.000 1.000 

3800221000 38 Meat, game 0.010000 1.000 1.000 

3600222000 36 Milk, fat 0.010000 1.000 1.000 

3600222001 36 Milk, fat-baby food/infant formu 0.010000 1.000 1.000 

3600223000 36 Milk, nonfat solids 0.010000 1.000 1.000 

3600223001 36 Milk, nonfat solids-baby food/in 0.010000 1.000 1.000 

3600224000 36 Milk, water 0.010000 1.000 1.000 

3600224001 36 Milk, water-babyfood/infant form 0.010000 1.000 1.000 

3600225001 36 Milk, sugar (lactose)-baby food/ 0.010000 1.000 1.000 

3500339000 35 Sheep, meat 0.010000 1.000 1.000 

3500339001 35 Sheep, meat-babyfood 0.010000 1.000 1.000 

3500340000 35 Sheep, meat byproducts 0.050000 1.000 1.000 

3500341000 35 Sheep, fat 0.010000 1.000 1.000 

3500341001 35 Sheep, fat-babyfood 0.010000 1.000 1.000 

3500342000 35 Sheep, kidney 0.050000 1.000 1.000 

3500343000 35 Sheep, liver 0.050000 1.000 1.000 

1500344000 15 Sorghum, grain 0.800000 1.000 1.000 

1500345000 15 Sorghum, syrup 0.800000 1.000 1.000 

8601000000 86A Water, direct, all sources 0.492000 1.000 1.000 

8602000000 86B Water, indirect, all sources 0.492000 1.000 1.000 

U.S. EPA Ver. 3.16, 03-08-d

DEEM-FCID Chronic analysis for NICOSULFURON NHANES 2003-2008 2-day

Residue file name: C:\Documents and Settings\MNEGUSSI\My Documents\DEEM Version 

3.16\Nicosulfuron\Chronic_Nicosulfuron2015PRA.R08

 Adjustment factor #2 NOT used.

Analysis Date 05-12-2015/09:34:25 Residue file dated: 05-12-2015/09:33:56

Reference dose (RfD, Chronic) = 1.25 mg/kg bw/day

COMMENT 1: Scoping-PRA EDWC-SU Coarse Screen Estimate

===============================================================================

 Total exposure by population subgroup

-------------------------------------------------------------------------------

 Total Exposure

 -----------------------------------

 Population mg/kg Percent of 
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 27 of 32

 Subgroup body wt/day Rfd 

-------------------------------------- ------------- ----------------

Total US Population 0.010525 0.8%

Hispanic 0.010116 0.8%

Non-Hisp-White 0.010809 0.9%

Non-Hisp-Black 0.008724 0.7%

Non-Hisp-Other 0.012082 1.0%

Nursing Infants 0.009471 0.8%

Non-Nursing Infants 0.034776 2.8%

Female 13+ PREG 0.009892 0.8%

Children 1-6 0.013843 1.1%

Children 7-12 0.008975 0.7%

Male 13-19 0.007353 0.6%

Female 13-19/NP 0.008144 0.7%

Male 20+ 0.009762 0.8%

Female 20+/NP 0.010956 0.9%

Seniors 55+ 0.010076 0.8%

All Infants 0.026963 2.2%

Female 13-50 0.010418 0.8%

Children 1-2 0.015634 1.3%

Children 3-5 0.013125 1.0%

Children 6-12 0.009434 0.8%

Youth 13-19 0.007753 0.6%

Adults 20-49 0.010451 0.8%

Adults 50-99 0.010280 0.8%

Female 13-49 0.010407 0.8%
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 28 of 32

Appendix C. Physical/Chemical Properties of Nicosulfuron and Metabolites

TABLE C.1. Physicochemical Properties of Nicosulfuron. 

Parameter Value Reference

Melting point/range 183.3 ± 0.3°C MRID #47632204

Ph 4.5 MRID #47632204

Density 1.441 ± 0.006 g/cm3relative density MRID #47632204

Water solubility (at 25°C) Anhydrous form (g/L)

pH 5 = 0.36

pH 7 = 12.2

pH 9 = 39.1

Monohydrate form 

(g/L)

pH 5 = 0.42

pH 7 = 7.4

pH 9 = 47.96

MRID #47632204

Solvent solubility (at 28°C) Solubility g/L

Acetone 18

Acetonitrile 23

Benzene 1.7

Chloroform 64

Dichloromethane 160

Dimethylformamide 64

Ethanol 4.5

Ethyl acetate 3.8

Hexane <0.02

Methanol 0.44

2-Propanol 1.2

Tetrahydrofuran 26

Toluene 0.37

Xylenes 0.2

MRID #47632204

Vapor pressure (at 25°C) 1.2 x 10-16 Torr MRID #47632204

Dissociation constant, pKa 4.22 MRID #47632204

Octanol/water partition 

coefficient, KOW (at 25°C)

pH 5 = 0.44

pH 7 = 0.02

pH 9 = 0.007

MRID #47632204

UV/visible absorption spectrum 

(at 20°C)

No absorbance maxima at or above 290 nm for 

acidic, basic or neutral solutions. 

MRID #47632204
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 29 of 32

TABLE C.2. Chemical Names and Structures of Nicosulfuron and Metabolites. 

Company Code; 

Common Name

Chemical Name Chemical Structure

IN-V9367; pyridine 

sulfonamide

[2-aminosulfonyl]-N,N-dimethyl-3-

pyridinecarboxamide

IN-HYY21 or AUSN

2-[[[[(Aminoiminomethyl) 

amino]carbonyl]amino]sulfonyl]-

N,N-dimethyl-3-

pyridinecarboxamide

IN-37740 2-[[(3,4-dihydro-6-methoxy-4-

oxopyrimidin-2-

yl]aminocarbonyl]aminosulfonyl]-N, 

N-dimethyl-3-pyridinecarboxamide

N

O

N

H3C CH3

S

NH2

O

O
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 30 of 32

Appendix D. Review of Human Research

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 are subject to ethics review 

pursuant to 40 CFR §26, have received that review, and are compliant with applicable ethics 

requirements. For certain studies that 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: 

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

http://www.epa.gov/pesticides/science/post-app-exposure-data.html.
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 31 of 32

Appendix E. International Harmonization

TABLE E.1. Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR 180.454

Plants/Livestock: nicosulfuron, 3-

Pyridinecarboxamide, 2-[[[[(4,6-dimethoxy2-pyrimidinyl)amino] 

carbonyl]amino]sulfonyl]-N,N-dimethyl

2[[[[(4,6-dimethoxy-2-

pyrimidinyl)amino]carbonyl]

amino]sulfonyl]-N,Ndimethyl-3-

pyridinecarboxamide

None

Commodity

Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico1 Codex

Cattle, fat 0.01

Cattle, meat 0.01

Cattle, meat byproducts 0.05

Corn, field, forage 0.1

Corn, field, grain 0.1 0.1 corn

Corn, field, stover 0.1

Corn, pop, grain 0.1

Corn, pop, stover 0.1

Corn, sweet, forage 0.1

Corn, sweet, kernel plus cob 

with husks removed

0.1

Corn, sweet, stover 0.1

Goat, fat 0.01

Goat, meat 0.01

Goat, meat byproducts 0.05

Grass, forage 9.0

Grass, hay 25.0

Horse, fat 0.01

Horse, meat 0.01

Horse, meat byproducts 0.05

Milk 0.01

Sheep, fat 0.01

Sheep, meat 0.01

Sheep, meat byproducts 0.05

MRLs with No US Equivalents

Blueberries 0.05

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.
Nicosulfuron Human Health Risk Assessment DP No. D427029

Page 32 of 32

Appendix F. DFR Data Waiver Rationale

Dislodgeable Foliar Residue (DFR): In accordance with 40 CFR §158, DFR data are required

for all occupational (e.g., crop, nursery, greenhouse use sites) or residential (e.g., ornamental and 

vegetable gardens, pick your own farms, retail tree farms) uses that could result in postapplication exposure to foliage. In the absence of chemical-specific DFR data, EPA uses default 

values. The 2012 Standard Operating Procedures for Residential Pesticide Exposure 

Assessment includes an analysis of a number of DFR studies, which resulted in the selection of a 

revised default values for the fraction of the application rate available for transfer after a foliar 

application (FAR). These values are based on an analysis of 19 DFR studies. Since that time, the 

Agricultural Re-entry Task Force has submitted information (MRID 49299201) that corrects an 

application rate error made in the original submission of “ARF039 – Determination of Dermal 

and Inhalation Exposure to Reentry Workers During Chrysanthemum Pinching in a Greenhouse” 

(EPA MRID 45344501). As a result, the range of FAR values was revised from 2% - 89% to 2% 

- 47%. In the data, a large range of transferability is observed and this variability can potentially 

be attributable to many factors such as active ingredient; formulation; field conditions in the 

studies; weather conditions (e.g., humidity); or many other difficult to quantify factors. 

Although witnessed across multiple chemicals, this range in FAR values is not expected when 

considering DFR data for a single chemical. At this time, the ARTF submission did not alter the 

selection of 25% as the reasonable, high-end default value. Because DFR data are not available 

for nicosulfuron, EPA is using the default value of 25%. Although there may be a small degree 

of uncertainty in the use of the default DFR value for nicosulfuron (i.e., there is a small chance 

that the FAR value may exceed the applicable default value), it is likely that the health-protective 

aspects of EPA’s occupational post-application assessment methodology will more than 

compensate for this potential uncertainty. For example, when assessing residential and 

occupational post-application exposure to gardens and ornamentals, EPA assumes the following: 

exposures occur to zero-day (i.e., day of application) residues every day of the assessed 

exposure duration (i.e., EPA assumes that no dissipation or degradation occurs, it doesn’t rain, 

etc); individuals perform the same post-application activities performed in the transfer 

coefficient study day after day (e.g., weeding, harvesting, pruning, etc.); and individuals engage 

in these post-application activities for a high-end amount of time every day (represented by data 

reflecting time spent gardening based on survey data).

Given the conservatisms discussed above and the potential compounding nature of these 

conservatisms, EPA is able to rely upon the calculated exposure estimates with confidence that 

exposure is not being underestimated. 

Since the highest estimated occupational post-application exposure using default DFR values for 

nicosulfuron is minimal in comparison to the level of concern (i.e., the calculated MOE is greater 

than 2 times higher than the level of concern, MOE = 3,700 compared to the LOC of 100); EPA 

is waiving the 40 CFR DFR data requirement. In this instance, it is unlikely that chemicalspecific DFR data would be needed to further refine exposure assessments or would add 

appreciably to our overall understanding of the availability of dislodgeable foliar pesticide 

residues for nicosulfuron.