Page 3 of 21

The residue chemistry database is complete for nicosulfuron risk assessment. HED has 

evaluated all submitted studies addressing prior deficiencies and has deemed the requirements 

satisfied. 

A new risk assessment may be needed pending the evaluation of the submitted toxicology studies

and the re-evaluation of databases using current policies. Occupational exposure assessments 

may need to be reassessed to incorporate current occupational exposure policies, currently 

registered maximum application rates, and any changes to the nicosulfuron toxicological 

endpoints. In addition, the Agency may need to consider changes that consider off-target 

movement of pesticides into residential settings. A new version of DEEM (Version 3.04) will be

used in dietary exposure assessments in the future. However, any potential changes in the 

DEEM model will not significantly affect the dietary exposure estimates for nicosulfuron. 

Introduction

Nicosulfuron is a selective herbicide belonging to the sulfonylurea group of herbicides. It 

inhibits the action of the plant enzyme, ALS, which is not found in mammals (including 

humans). Nicosulfuron is used for the pre- and post-emergent control of annual weeds in 

selected agricultural crops and non-residential areas. Nicosulfuron is sold in the US as liquid and 

dry flowable (DF)/water-dispersible granule (WDG) formulations. Some DF formulations are 

manufactured in water soluble bag (WSB) packaging.

The most recent risk assessment for nicosulfuron was conducted in 2009 (M. Doherty, D360807, 

10/27/2009). A Tolerance Reassessment and Risk Management Decision (TRED) was 

conducted in 2004 (D. Hrdy, D302694, 11/30/2004). Refer to Attachment 1 for the chemical 

identity of the parent compound, and structures of parent and metabolites. 

Hazard Identification/Toxicology

Per the 2007 revised 40 CFR Part 158 Toxicology data requirements, the neurotoxicity battery 

(acute and subchronic neurotoxicity studies) and an immunotoxicity study are all required for 

nicosulfuron registration. The Agency has now received the required studies; the data will be 

reviewed and the results will be incorporated into the Preliminary Risk Assessment during the 

registration review of nicosulfuron. In the case of inhalation and dermal toxicity, the registrant 

has submitted waiver requests which have been granted (TXR 0050011). 

Nicosulfuron exhibits low acute 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. 

Subchronic or chronic dietary administration of doses exceeding the limit dose did not produce 

adverse effects in rats or mice. Chronic administration in the diet to dogs produced mild effects 

(decreased body weight gains in males and increases in the relative liver and kidney weights) at 

the limit dose. No findings were reported in dogs following subchronic dosing at comparable 

dietary levels. The toxicology database for nicosulfuron suggests that this herbicide possesses 
Page 4 of 21

relatively low mammalian toxicity which is consistent with its herbicidal MOA – inhibition of a 

critical enzyme not found in mammals. 

No developmental or reproductive effects were observed in rats. However, in rabbits, maternal 

toxicity (clinical signs, decreased body weight gain during dosing, increased abortions), postimplantation loss, and decreases in fetal body weight were observed. Developmental effects 

(decreased fetal body weight) were only observed at maternally toxic doses. In clinical 

observations of repeat-dose studies, there were no indications of neurotoxic or immunotoxic 

effects. 

Nicosulfuron is classified as “not likely to be carcinogenic” to humans. 

The points of departure (PoDs) and toxicity endpoints from the most recent risk assessment (M. 

Doherty, D360807, 10/27/2009) are summarized in Attachment 4, Tables 4.1 and 4.2. The 

toxicity endpoints and PoDs for risk assessment were selected for chronic dietary, and short- and 

intermediate-term dermal and inhalation scenarios. 

Conclusions: The toxicology database is adequate for FQPA assessment. The Agency has now

received the required neurotoxicity battery and immunotoxicity study. The data will be reviewed

and the results will be incorporated into the Preliminary Risk Assessment during registration 

review of nicosulfuron. An inhalation toxicity waiver has been granted based on low hazard and 

low exposure; the registered use resulting in the highest expected exposure yielded an MOE of 

30,000. A dermal toxicity waiver has also been granted based low dermal absorption and hazard 

and high MOEs in excess of 1000.

Dietary Exposure

The most recent dietary exposure assessment (M. Doherty, D369742, 10/15/2009) was 

conducted using the Dietary Exposure Evaluation Model DEEM-FCIDTM Version 2.03. No 

acute dietary toxicity endpoints were identified for nicosulfuron; therefore, only a chronic dietary 

exposure assessment was conducted. The unrefined chronic dietary (food and drinking water) 

exposure assessment included residues in corn (food use) and livestock commodities (meat and 

milk) resulting from consumption of nicosulfuron-treated feed items. The residue levels used in 

the assessment for all commodities were tolerance-level. As explained in Attachment 3, the 

assessment was conducted using the assumption that 100% of the crops were treated (100%CT) 

and using default (DEEM 7.81) processing factors. 

The Environmental Fate and Effects Division (EFED) provided estimated drinking water 

concentrations (EDWCs) of nicosulfuron in water. The most conservative estimate of 

nicosulfuron in water, from its use on corn, was incorporated directly into the chronic dietary 

assessment. A Tier 1 drinking water assessment for the use on corn was performed using the 

FQPA Index Reservoir Screening Tool (FIRST) and Screening Concentration In Ground Water 

(SCIGROW) modeling. EDWCs for nicosulfuron are based on estimated surface water residues, 

and are not expected to exceed 0.685 ppb (0.000685 ppm). 
Page 5 of 21

The chronic dietary (food and drinking water) exposures to nicosulfuron were below HED’s 

level of concern for the general US population and all population subgroups. All dietary risk 

estimates were <1% of the chronic population adjusted dose (cPAD), and therefore are not of 

concern. 

HED classified nicosulfuron as “not likely to be a human carcinogen;” therefore, a quantification 

of human cancer risk was not conducted. 

The residue chemistry database is sufficient to support current tolerances. For corn, the nature of 

the residue in plants and livestock has been defined, and adequate enforcement methods are 

available. Adequate storage stability, field trial, and rotational crop data are also available. 

Adequate residue chemistry data are available to support tolerances for residues of nicosulfuron 

in/on grass commodities. However, additional storage stability studies (860.1380), residue 

decline studies (860.1500) and field accumulation in rotational crops studies (860.1900) were 

required (M. Doherty, D360807, 10/27/2009) as conditions of registration. HED has evaluated 

all submitted studies addressing prior deficiencies and has deemed the requirements satisfied. 

Conclusions:

The residue chemistry database is sufficient to support current tolerances of nicosulfuron. The 

re-evaluation of dietary exposure using a new version of DEEM (Version 3.04) is unlikely to 

change the overall dietary risk conclusion for nicosulfuron. Any potential changes in the DEEM 

model will not significantly affect the dietary exposure estimates. 

Residential and Occupational Exposure

Currently, nicosulfuron is only registered for use on sorghum in seed propagation, corn, and 

grasses in non-residential areas.

Residential Exposure

Nicosulfuron is not registered for use in residential settings.

Conclusions: Because nicosulfuron is not registered for use in residential settings, there is 

currently no risk concern for residential exposure. If exposure data and methodologies for 

estimating exposure have changed for issues such as volatilization and spray drift, then a new 

exposure assessment may be required.

Aggregate Risk Assessment

Aggregate assessments consider exposures from food, drinking water, and residential uses. 

Since there are no residential uses of nicosulfuron, aggregate risk for all exposure durations 

consists of only food and drinking water. For nicosulfuron, there is no endpoint established for 

acute exposure, and it has been determined to be a “not likely” human carcinogen; therefore

neither an acute nor a cancer aggregate risk assessment is required. In the most recent human 

health risk assessment (M. Doherty, D360807, 10/27/2009), risk estimates from chronic dietary 

exposure from food and drinking water were not of concern. 
Page 6 of 21

Conclusions: Unless toxicity endpoints for chronic dietary exposure are changed or acute dietary 

exposure toxicity endpoints are identified in newly submitted toxicity studies, a new aggregate 

risk assessment will not be necessary. 

Occupational Exposure

Nicosulfuron is registered for use on the following crops: field corn, sweet corn, and popcorn

from post-emergence up to the 20” stage; established sorghum in seed propagation fields; and 

established grasses. There is potential for short- and intermediate-term occupational exposure to 

nicosulfuron during handling (mixing, loading, and applying) and post-application activities. 

Occupational handler exposure assessments have been conducted for nicosulfuron DF and liquid 

formulations. 

Occupational Handlers

Previous occupational handler exposure and risk assessments were conducted for nicosulfuron 

use on corn, but not for use on sorghum, and not at the highest application rate registered for use 

on grasses. However, the corn assessment would be protective of exposure to nicosulfuron 

application to sorghum; the registered formulation and application methods are the same for both 

crops, and the application rate for sorghum is lower than for corn. An up-to-date occupational 

assessment is needed for use on grasses at the highest registered application rate, and may be 

needed for all registered uses to account changes in occupational assessment policies (unit 

exposures and TC), and to account for any changes to the nicosulfuron toxicological endpoints

after review of the submitted toxicity studies. If the re-evaluation of nicosulfuron endpoints does 

not change the endpoints selected for risk assessment, the occupational exposure assessment

should rely on the NOAEL from the chronic dog study which is regarded as a more accurate PoD 

based on dose-selection and dose spread (125 mg/kg/day) (M. Dow, D362708, 4/01/2009). 

All current exposure estimates at baseline personal protective equipment (PPE) (single layer 

clothing, no gloves, and no respirator) result in risk estimates which are not of concern. Because 

the same study and same PoD were chosen for dermal and inhalation exposure assessments, 

MOEs and exposures can be aggregated where appropriate. Combined (dermal + inhalation)

MOEs for nicosulfuron to registered use sites ranged from 1,300 to 93,000 at baseline PPE. 

Attachment 5 provides the occupational handler scenarios for nicosulfuron and whether or not 

the scenario has been assessed by HED.

Occupational Post-Application

Occupational post-application exposure can occur via the dermal and/or inhalation route. Postapplication dermal exposures from contact with treated corn and grasses were estimated. The 

MOEs for post-application exposure to the registered use sites of nicosulfuron ranged from 6,200 

to 8,400 and were not of concern. However, new assessments may be needed for postapplication scenarios at the highest registered application rate for grasses, and because HED 

policies have changed, i.e., new transfer coefficients (TCs) have been established. 
Page 7 of 21

Residential bystander inhalation exposures resulting from off-site transport (e.g., spray drift or 

volatilization) may occur as a result of applications of nicosulfuron. The Agency is in the process 

of evaluating these types of exposures 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. The need for a bystander inhalation risk 

assessment for nicosulfuron should be examined during registration review.

Conclusions: There is sufficient information available to assess occupational exposure. An upto-date occupational assessment is needed for use on grasses at the highest registered application 

rate, and may be needed for all registered uses to account for changes in occupational assessment 

policies (unit exposures and TCs), to assess using the most accurate PoD (NOAEL = 125 

mg/kg/day), or to incorporate any changes in toxicological endpoints upon review of recently

submitted toxicity studies. Dislodgeable foliar residues studies would refine the occupational 

post-application assessment, but, based on the current use pattern of nicosulfuron, are not 

required at this time. If the use pattern or HED policies change, DFR studies may be required on 

corn, sorghum and grasses. 

Endocrine Disruptor Screening Program

As required by the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal 

Food, Drug, and Cosmetic Act (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, 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 

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 
Page 8 of 21

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. Nicosulfuron 

is not among the group of 58 pesticide active ingredients on the initial list to be screened under 

the EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data 

call-ins, requiring the submission of EDSP screening assays for nicosulfuron. For further 

information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, 

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

http://www.epa.gov/endo/.

Public Health and Pesticide Epidemiology Data

The evaluation of the OPP Incident Data System (IDS) (S. Recore, D398572, 2/14/12) indicated 

that no incidents were identified in the United States from January 1, 2006 through December 

14, 2011 for the single chemical nicosulfuron. In the aggregate IDS from January 1, 2006 to 

December 14, 2011, 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; however, a high frequency of incidents indicates there is a 

high potential for exposure and vice versa. 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.

Tolerance Assessment and International Harmonization

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, including its metabolites and degradates, 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. 

Compliance with the tolerance levels is to be determined by measuring only nicosulfuron.

No Codex or Mexican MRLs are established for residues of nicosulfuron; Canadian MRLs are 

established for blueberries and corn, and are expressed in terms of nicosulfuron. US tolerances 

and Canadian MRLs are harmonized for field corn grain (see Attachment 2, Tables 2.1 and 2.2). 

Environmental Justice
Page 9 of 21

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

human health risk assessment, in accordance with US Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf).

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 Continuing Survey of Food Intake by Individuals (CSFII) 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, season of the year, ethnic group, and region of the 

country. 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.

Cumulative 

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to nicosulfuron and any other substances and nicosulfuron does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this action, therefore, EPA has not 

assumed that nicosulfuron has a common mechanism of toxicity with other substances. For 

information regarding EPA’s efforts to determine which chemicals have a common mechanism 

of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements 

released by EPA’s Office of Pesticide Programs concerning common mechanism determinations 

and procedures for cumulating effects from substances found to have a common mechanism on 

EPA’s website at http://www.epa.gov/pesticides/cumulative/.

Human Studies

Past nicosulfuron risk assessments rely in part on data from studies in which adult human 

subjects were intentionally exposed to a pesticide or other chemical to determine their dermal 

and inhalation exposure. Many such studies, involving exposure to many different pesticides, 

comprise generic pesticide exposure databases such as the Pesticide Handlers Exposure 

Database (PHED) and the Agricultural Reentry Task Force (ARTF) Database. EPA has 

reviewed all the studies supporting these multi-pesticide generic exposure databases, and has 

found no clear and convincing evidence that the conduct of any of them was either 

fundamentally unethical or significantly deficient relative to the ethical standards prevailing at 

the time the research was conducted. All applicable requirements of EPA’s Rule for the 
Page 10 of 21

Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied, and there is 

no regulatory barrier to continued reliance on these studies.

Data Requirements

As shown in References below, four human health risk assessments have been conducted for 

nicosulfuron between 2004 and 2010. Provided the submitted neurotoxicity and immunotoxicity 

data are found to be acceptable, there are no outstanding data gaps associated with the 

toxicology, exposure and residue chemistry requirements. 

References

Memoranda Relevant to Registration Review of Nicosulfuron

Author Barcode 

(DP#)

Date Title

Risk Assessments

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. 

Incident Reports

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

Residue Chemistry

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. 

M. Doherty D369742 10/15/2009 Nicosulfuron- Dietary Exposure and Risk Analysis to Evaluate a 

New Use Request for Grasses.

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 

Noted in HED Review D360897.

Occupational Residential Exposure

M. Crowley D302620 11/17/2004 Nicosulfuron Occupational and Residential Exposure Assessment for 

the Tolerance Reregistration Eligibility Decision (TRED) Document 

for Post 84 Pesticide.

S. Oonnithan D339818 8/14/2007 Nicosulfuron: Occupational Exposure Assessment for the 

Registration of a New Formulation, Cheminova Nicosulfuron 2L 

(EPA File Symbol 67760-TU) for Use on Corn.
Page 11 of 21

Memoranda Relevant to Registration Review of Nicosulfuron

Author Barcode 

(DP#)

Date Title

M. Dow D362708 4/1/2009 Nicosulfuron – Human Occupational Exposure/Risk Assessment for 

the Proposed FIFRA Section 18 Use of Nicosulfuron on 

Bermudagrass Pasture and Hayfields in Oklahoma and Texas.

Attachments

1. Chemical Identity Tables

2. Tolerance Summary Table

3. Percent Crop Treated Data Comparison Table

4. Endpoint Selection Table

5. Residential Exposure Tables

6. Occupational Exposure Tables

7. Outstanding Deficiencies to be Addressed by the Registrants
Page 12 of 21

Attachment 1

Chemical Identity Table

Table 1.1. Chemical Identity – Nicosulfuron

Common Name Nicosulfuron

Chemical Name (CAS) 2-[[[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfonyl]-N,Ndimethyl-3-pyridinecarboxamide

IUPAC name 2-[(4,6-dimethoxypyrimidin-2-ylcarbamoyl)sulfamoyl]-N,Ndimethylnicotinamide;

1-(4,6-dimethoxypyrimidin-2-yl)-3-(3-dimethylcarbamoyl-2-pyridylsulfonyl)urea

PC Code 129008

Chemical Abstracts No. 111991-09-4

Registration Review Case 

No.

7227

Chemical Class Herbicide

Chemical structure

Table 1.2. 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 (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

N

O

N

H3C CH3

S

NH NH

N

N O

O

CH3

CH3

O O

O
Page 13 of 21

Table 1.2. Physicochemical Properties of Nicosulfuron

Parameter Value Reference

Solvent solubility (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 (25 °C) 1.2 x 10-16 mm Hg 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 No absorbance maxima at or above 290 nm at 20 

°C for acid, basic, and neutral solutions. 

MRID 47632204
Page 14 of 21

Attachment 2

Tolerance/MRL Table

No Codex or Mexican MRLs are established for residues of nicosulfuron; Canadian MRLs are 

established in blueberries and corn, and are expressed in terms of nicosulfuron. Harmonization 

of tolerances is not an issue for this tolerance petition. 

Nicosulfuron (129008, 02/09/2012)

Table 2.1. Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex2

40 CFR 180.454

Plants/Livestock: nicosulfuron, 3-

Pyridinecarboxamide, 2-[[[[(4,6-

dimethoxy-2-pyrimidinyl)amino] 

carbonyl]amino]sulfonyl]-N,Ndimethyl

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

pyrimidinyl)amino]carbon

yl]

amino]sulfonyl]-N,Ndimethyl-3-

pyridinecarboxamide

None

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

US Canada Mexico1 Codex2

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

Completed: M. Negussie; 02/09/2012
Page 15 of 21

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

2

* = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. F = measured in the milk fat. MRLs indicated as proposed have not been finalized by the 

CCPR and the CAC.
Page 16 of 21

Attachment 3

Percent Crop Treated Data Comparison Tables

The most recent dietary exposure assessment (M. Doherty, D369742, 10/15/2009) was 

conducted using the assumption for all registered/proposed crops that 100% of the crop was 

treated (100%CT). 
Page 17 of 21

Attachment 4

Summary of Endpoints, Points of Departure, and Toxicology Data Requirements for 

Nicosulfuron

Table 4.1. Summary of Toxicological Doses and Endpoints for Nicosulfuron for Use in Dietary and NonOccupational 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 (All 

populations, including 

Infants and Children and 

Females 13-49 years of 

age)

An endpoint of concern attributable to a single dose was not identified.

Chronic Dietary (All 

Populations)

NOAEL=125 

mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 1x

Chronic RfD = 

cPAD = 

1.25mg/kg/day

One Year Dog - Decreased body 

weight gain in males and the 

statistically significant increase in the 

relative liver and kidney weights of 

males at the LOAEL of 500 

mg/kg/day.

Incidental Oral This risk assessment is not required. There are no residential uses of nicosulfuron.

Dermal (all durations) This risk assessment is not required. There are no residential uses of nicosulfuron.

Inhalation (all durations) This risk assessment is not required. There are no residential uses of nicosulfuron.

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). FQPA SF = FQPA Safety Factor. N/A = not 

applicable.

Table 4.2. Summary of Toxicological Doses and Endpoints for Nicosulfuron for Use in 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

Dermal (short- and 

intermediate-term)

NOAEL=125 

mg/kg/day

DAF = 100% 

(default)

UFA= 10x

UFH= 10x

Occupational 

LOC for 

MOE < 100

One Year Dog - Decreased body 

weight gain in males and the 

statistically significant increase in the 

relative liver and kidney weights of 

males administered 500 mg/kg/day 

(LOAEL).
Page 18 of 21

Table 4.2. Summary of Toxicological Doses and Endpoints for Nicosulfuron for Use in 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

Inhalation (short- and 

intermediate-term)

NOAEL=125 

mg/kg/day

IAF = 100% 

(default)

UFA= 10x

UFH= 10x

Occupational 

LOC for 

MOE < 100

One Year Dog - Decreased body 

weight gain in males and the 

statistically significant increase in the 

relative liver and kidney weights of 

males administered 500 mg/kg/day 

(LOAEL).

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). FQPA SF = FQPA Safety Factor. MOE = 

margin of exposure. LOC = level of concern. N/A = not applicable. DAF = dermal absorption factor. IAF = 

Inhalation absorption factor.
Page 19 of 21

Toxicology Data Requirements

The requirements (40 CFR 158.500) for food uses of nicosulfuron are in Table 4.3. Use of the new guideline 

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

Table 4.3. Summary of Toxicological Data Requirements for Nicosulfuron 

Test

Technical

Required Satisfied

870.1100 Acute Oral Toxicity

870.1200 Acute Dermal Toxicity

870.1300 Acute Inhalation Toxicity

870.2400 Primary Eye Irritation

870.2500 Primary Dermal Irritation

870.2600 Dermal Sensitization

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

870.3100 Oral Subchronic (rodent)

870.3150 Oral Subchronic (nonrodent)

870.3200 21-Day Dermal

870.3250 90-Day Dermal

870.3465 90-Day Inhalation*

Yes

Yes

Yes

No

Yes

Yes

Yes

*

-

*

870.3700a Developmental Toxicity (rodent)

870.3700b Developmental Toxicity (nonrodent)

870.3800 Reproduction

Yes

Yes

Yes

Yes

Yes

Yes

870.4100a Chronic Toxicity (rodent)

870.4100b Chronic Toxicity (nonrodent)

870.4200a Oncogenicity (rat)

870.4200b Oncogenicity (mouse)

870.4300 Chronic/Oncogenicity

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

870.5100 Mutagenicity—Gene Mutation - bacterial

870.5300 Mutagenicity—Gene Mutation - mammalian

870.5385 Mutagenicity—Mammalian Bone Marrow 

 Chromosome Aberration Aberrations

870.5550 Mutagenicity—Unscheduled DNA Synthesis

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

**

**

-

870.7485 General Metabolism

870.7600 Dermal Penetration

870.7800 Immunotoxicity

Yes

No

Yes

Yes

-

**

* The requirement for this study has been waived (TXR 0050011) . 

** Study Under Review
Page 20 of 21

Attachment 5

Occupational Exposure Table

Table 5.1. Occupational Handler Exposure Scenarios for Nicosulfuron

Crop/Use Site Formulation 

Typea Application Method Max Application Rate

Scenario Assessed or Coveredc

M/L A M/L/A Flagger

Field Corn, Sweet Corn, 

Popcorn

DF Aerial

0.062 lb ai/A

Y Y N/A Y

Groundboom Y Y N/A N/A

Liquid Aerial Y

d Y N/A Y

Groundboom Y

d Y N/A N/A

WSB Aerial Y Y N/A Y

Groundboom Y Y N/A N/A

Bermudagrassb DF

Aerial (broadcast)

0.0703 lb ai/A

N N N/A N

Groundboom 

(broadcast) N N N/A N/A

Backpack sprayer (spot 

treatment)

0.088 lb ai/ 100 gal

N N N N/A

Hand held sprayer 

(spot treatment) N N N N/A

Truck-mounted sprayer 

(spot treatment) N N N N/A

Sorghume DF Aerial 0.047 lb ai/A

Y Y N/A Y

Groundboom Y Y N/A N/A

a DF = dry flowable, WSB = dry flowable in water soluble packaging

b Includes rights-of-way, agricultural uncultivated areas, airports, landing fields, grass/forage/fodder/hay, industrial/construction areas, 

intermittently flooded areas when no water is present, marshes/swamps/bogs after water has receded, non-agricultural rights of 

way/fences/hedgerows, and sewage disposal areas.

c Indicating that an occupational exposure assessment was or was not conducted for the proposed use at the time of the petition. However, the 

occupational exposure scenarios were may not have been assessed based on current ORE policies. An up-to-date occupational assessment may be 

needed, accounting for the changes in policies, unit exposures and TCs.

d Would be covered by the DF assessment.

e Would be covered by the corn assessment 

N= No, Y= Yes, N/A = Not Applicable
Page 21 of 21

Table 5.2. Occupational Post-Application Exposure Scenarios for Nicosulfuron

Crop/Use Site Application Rate 

Assessed (lb ai/A) Activity TC (cm2/hr)

Scenario Covered or 

Assesseda

Forage Plants/Grasses 0.053

Scouting (early season, postemergence)

1100 N

Small Grain Crops

(Sorghum) 0.053 1100 Y

Corn 0.062 1000 Y

a Indicating that an occupational exposure assessment was or was not conducted for the proposed use at the time of the petition. 

However, the occupational exposure scenarios may not have been assessed based on current ORE policies and using current assessment 

inputs (TCs). An up-to-date occupational assessment may be needed, accounting for the changes in policies, unit exposures, and TCs.

N= No, Y= Yes,