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 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460 

 OFFICE OF 

PREVENTION, PESTICIDES 

AND TOXIC SUBSTANCES 

MEMORANDUM

Date: 7/14/09 

SUBJECT: Nicosulfuron: Human Health Risk Assessment for Proposed Section 18 Use on 

Bermudagrass. 

PC Code: 129008 DP Num: D361732 

Decision No.: 405771 Registration No.: NA 

Petition No.: 09OK02 Regulatory Action: Section 18 

Registration 

Risk Assessment Type: Single Chemical 

Aggregate 

Case No.: NA 

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

MRID No.: NA 40 CFR: §180.454 

FROM: W. Cutchin, Chemist 

Alternative Risk Integration Assessment (ARIA) Team 

Risk Integration, Minor Use, and Emergency Response Branch (RIMUERB) 

Registration Division (RD; 7505P) 

 

THROUGH: C. Swartz, Branch Chief 

 L. Hansen, Ph.D., Biologist 

 Registration Action Branch II (RAB II) 

 Health Effects Division (HED; 7509P) 

TO: B. Madden, Risk Manager 

 RIMUERB/RD (7505P) 

 
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Table of Contents

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

2.0 Ingredient Profile................................................................................................................. 6 

2.2 Structure and Nomenclature ...................................................................................... 7 

2.3 Physical and Chemical Properties.............................................................................. 7 

3.0 Hazard Characterization/Assessment................................................................................ 8 

3.1 Hazard and Dose-Response Characterization............................................................ 8 

3.1.2 Toxicological Effects................................................................................... 10 

3.5 Hazard Identification and Toxicity Endpoint Selection........................................... 10 

3.5.5 Level of Concern for Margin of Exposure................................................... 10 

3.5.6 Recommendation for Aggregate Exposure Risk Assessments .................... 10 

3.5.8 Summary of Toxicological Doses and Endpoints for Nicosulfuron for Use in 

Human Risk Assessments........................................................................................ 10 

4.0 Public Health and Pesticide Epidemiology Data............................................................. 12 

5.0 Dietary Exposure/Risk Characterization ........................................................................ 12 

5.1 Pesticide Metabolism and Environmental Degradation........................................... 12 

5.1.1 Metabolism in Primary Crops...................................................................... 12 

5.1.2 Metabolism in Rotational Crops .................................................................. 12 

5.1.3 Metabolism in Livestock.............................................................................. 13 

5.1.4 Analytical Methodology .............................................................................. 13 

5.1.5 Environmental Degradation......................................................................... 14 

5.1.6 Comparative Metabolic Profile.................................................................... 15 

5.1.7 Pesticide Metabolites and Degradates of Concern....................................... 15 

5.1.8 Drinking Water Residue Profile................................................................... 15 

5.1.9 Food Residue Profile.................................................................................... 16 

5.1.10 International Residue Limits...................................................................... 18 

5.2 Dietary Exposure and Risk ........................................................................................... 18 

5.2.1 Acute Dietary Exposure/Risk ........................................................................ 18 

5.2.2 Chronic Dietary Exposure/Risk ..................................................................... 18 

5.2.3 Cancer Dietary Risk....................................................................................... 19 

5.3 Anticipated Residue and Percent Crop Treated (%CT) Information............................. 19 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................... 19 

6.1 Other (Spray Drift, etc.)........................................................................................... 19 

7.0 Aggregate Risk Assessments and Risk Characterization............................................... 20 

8.0 Cumulative Risk Characterization/Assessment.............................................................. 20 

9.0 Occupational Exposure/Risk Pathway............................................................................. 20 

9.1 Short-Term Handler Risk......................................................................................... 21 

9.2 Short-/Intermediate-/Long-Term Postapplication Risk ........................................... 23 

10.0 Data Needs and Label Recommendations ....................................................................... 24 

References:...................................................................................................................................... 24 

Appendix A: Toxicology Assessment .......................................................................................... 26 

Appendix B: International Residue Status................................................................................. 30 
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1.0 Executive Summary

The Oklahoma Department of Agriculture, Food, and Forestry and the Texas Department of 

Agriculture have submitted a Section 18 petition proposing the use of nicosulfuron on 

Bermudagrass for control of sandbur. The proposed uses are for PastoraTM Herbicide (EPA Reg. 

No. not registered), a dry flowable (DF) formulation containing 3.19 lb ai/gal for multiple 

broadcast foliar applications at maximum seasonal rates of 0.0878 lb ai/A on Bermudagrass. 

Foliar applications may be made using ground or aerial equipment. The use of spray adjuvants is 

required. There are no feeding restrictions for the use of nicosulfuron in Bermudagrass. 

Nicosulfuron [3-pyridinecarboxamide, 2-((((4,6-dimethoxypyrimidin-2-yl)aminocarbonyl) 

aminosulfonyl))-N,N-dimethyl] is a member of the sulfonylurea family of herbicides which 

includes, among others, halosulfuron, pirimisulfuron and chlorsulfuron. Nicosulfuron is used for 

control of weeds such as Johnsongrass, quackgrass, foxtails, shattercane, panicums, barnyardgrass, 

sandbur, pigweed, morning glory and others. Nicosulfuron’s herbicidal action is due to the 

inhibition of the enzyme acetolactate synthetase leading to the disruption of cell division and plant 

growth. The registered formulations of nicosulfuron include water dispersible granules, an 

emulsifiable concentrate, and suspension concentrates. 

Toxicology 

Nicosulfuron is of low acute toxicity by all routes of exposure (Category III or IV for acute 

lethality and irritation studies) and is not a skin sensitizer. In repeated dose studies by the oral 

route, nicosulfuron is minimally toxic. No effects were observed in rats or mice following either 

subchronic or chronic dietary administration of doses exceeding the limit dose. Chronic dietary 

administration to dogs produced minimal toxicity (in males, decreased body weight and increased 

relative liver and kidney weights), also at high doses. Nicosulfuron is not likely to be carcinogenic 

based on lack of tumorigenicity in rodent bioassays and lack of mutagenic effects in the in vitro

and in vivo genotoxicity assays. Nicosulfuron showed no developmental or reproductive effects in 

rats; in rabbits, developmental and maternal effects were observed at high doses. No effects 

indicating neurotoxicity or immunotoxicity were observed in any study. The low toxicity of 

nicosulfuron is consistent with poor oral absorption as observed in the rat metabolism study. 

Studies suitable for use in risk assessment were limited to the developmental study in rabbits and 

chronic study in dogs. An endpoint of concern attributable to a single dose was not identified from 

the toxicity database. The chronic oral dog study was selected for all exposure scenarios assessed 

for this proposed use, supported by the findings from the rabbit developmental toxicity study. 

This endpoint is protective of all populations including pre- and/or postnatal exposure. 

Uncertainty factors of 10X for intra- and 10X for interspecies variability, respectively, were 

applied to give a combined uncertainty factor of 100X in determining the chronic reference dose 

(RfD) and calculation of the Margins of Exposure (MOE) for Occupational/Residential Risk 

Assessments. 

The nicosulfuron HED team recommended reduction of the Food Quality Protection Act (FQPA) 

Safety Factor (SF) to 1x because there are no concerns and no residual uncertainties with regard to 

pre- and/or postnatal toxicity. The existing toxicology database for nicosulfuron is considered 

adequate for purposes of this risk assessment. Although there are several toxicology data gaps 

under the current (revised) 40 CFR Part 158 toxicology data requirements (immunotoxicity, rat 

acute and subchronic neurotoxicity, and rat 28-day inhalation and 21-day dermal toxicity studies), 

due to the lack of evidence of immunotoxicity or neurotoxicity in available studies, it is unlikely 

that these studies will identify a NOAEL below the dose currently selected for exposure 

assessments. Therefore, an additional safety factor (UFDB) for database uncertainty is not needed. 
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Residue Chemistry 

The nature of the residue in plants and livestock is adequately understood for the purposes of this 

action based on metabolism studies with corn and goats. The residue of concern for both risk 

assessment and tolerance enforcement purposes is nicosulfuron. The primary degradation 

pathway, with regard to water, was aerobic soil metabolism. Degradation rate and the resulting 

degradates under aerobic soil metabolism conditions depended on the pH of the soil. Nicosulfuron 

is more persistent in alkaline soils. 

CIBA-Geigy’s method, AG-499, a high performance liquid chromatography with ultra-violet 

detection (HPLC/UV) method, was found adequate for enforcement purposes. The procedure has 

a limit of detection (LOD) of 0.05 ppm. The method was recommended for inclusion in the 

Pesticide Analytical Manual Vol. II (PAM II). Grass forage and hay samples in the administrative 

materials submitted by DuPont in support of the Section 18 request were analyzed for nicosulfuron 

using procedures described in DuPont-17928, an HPLC with electrospray mass spectrometry/mass 

spectrometry (ESI-MS/MS) method. The method LOD and limit of quantitation (LOQ) were 

0.003 mg/kg and 0.010 mg/kg, respectively. A successful Independent Laboratory Validation 

(ILV) has been conducted. The method is adequate for data gathering purposes. 

The registrant submitted a volume of administrative materials for an upcoming petition (for 

Section 3 Registration) in support of this Section 18 action. The registrant has conducted thirteen 

residue field trials on Bermudagrass, brome, and fescue. Nicosulfuron 75WG was applied either 

as a single foliar broadcast application at the rate of 1.41 oz ai/A (0.088 lb ai/A), or as two foliar 

broadcast applications at the target rates of 0.938 oz ai/A (0.059 lb ai/A) and 0.469 oz ai/A (0.029 

lb ai/A). Non-ionic surfactants or nitrogen were included in the spray mixture in all applications. 

Samples were harvested the same day as the last application. Analysis of the samples was 

conducted using the method described in DuPont-17928. The registrant reported that the LOQ of 

the analytical method was 0.010 ppm and the LOD was 0.003 ppm (1/3 the LOQ). Nicosulfuron 

residues in grass forage and hay were reported as ranging from 0.032 ppm to 7.7 ppm and from 

0.11 ppm to 18.0 ppm, respectively. ARIA recommends for nicosulfuron time-limited tolerances 

on Bermudagrass, forage and hay at 10 ppm and 25 ppm, respectively, as a result of this Section 18 

use. 

Grass forage and hay are feed items for beef and dairy cattle. A dietary burden for cattle using the 

established tolerances for corn commodities as well as the proposed time-limited tolerances for 

Bermudagrass results in an exposure of 3.0 ppm for both beef cattle and 5.8 ppm for dairy cattle. 

Previously submitted metabolism studies using lactating goats dosed with nicosulfuron at a daily 

feeding level of approximately 60 ppm showed that uptake of residues was low for all tissues and 

organs. The highest residue level found, 0.1 ppm (0.04% of total dose), was in the liver. Using the 

dietary burden and the dosage and results of the metabolism study, residues would not be 

detectable in cattle commodities. Therefore, ARIA determines that as a result of this Section 18 

use, there would be no detectable residues of nicosulfuron in ruminants. There is no need for 

nicosulfuron cattle tolerances at this time. 

Grass feed items are not used for swine and poultry. Since the addition of grass feed items will not 

affect the swine or poultry diets, there is no need for nicosulfuron swine or poultry tolerances at 

this time. 

Drinking Water 
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The Ecological Fate and Effects Division (EFED) presented the Tier I Estimated Environmental 

Concentrations (EECs) for nicosulfuron, estimated using the models FQPA Index Reservoir 

Screening Tool (FIRST) for surface water and Screening Concentration In GROund Water

(SCIGROW) for groundwater in the human health risk assessment. For nicosulfuron, the surface 

water chronic value is 0.7 ppb and the groundwater screening concentration is 0.06 ppb based on 

the application on corn. 

Dietary Exposure 

Since no acute end point has been selected for nicosulfuron, an acute dietary exposure assessment 

was not required. 

Chronic dietary exposure is based on potential residues in food and drinking water. In the case of 

this Section 18 request, there are no human food items of regulable interest for Bermudagrass. 

ARIA has also determined that there will be no detectable nicosulfuron residues in livestock 

commodities. A previous chronic dietary (food + water) risk assessment was conducted for the 

general U.S. population and various population subgroups. Drinking water was incorporated 

directly into the dietary assessment using the chronic (annual average) concentration for surface 

water. Tolerance level residues were used along with 100 percent crop treated (%CT), and a single 

point estimate for drinking water, resulting in a conservative chronic exposure and risk assessment 

for nicosulfuron. The results from the overall chronic dietary risks using DEEM-FCIDTM analyses 

are below HED’s level of concern. The chronic population adjusted dose (cPAD) value for the 

general U.S. population is less than 1% and the most highly exposed population subgroup, children 

3-5, is also less than 1%.

Residential 

There are no residential uses for nicosulfuron; therefore, incidental oral, dermal, and inhalation 

exposure assessments are not required. 

Aggregate Risk 

The acute aggregate risk assessment takes into account exposure estimates from dietary 

consumption of nicosulfuron (food + drinking water). Since no acute endpoint has been identified 

for nicosulfuron an acute aggregate risk assessment is not required. Chronic aggregate risk takes 

into account exposure estimates from dietary consumption (food + drinking water), which is not of 

concern. Nicosulfuron is considered not likely to be carcinogenic, so there is no dietary or 

aggregate cancer risk associated with the proposed Section 18 use. 

Occupational Exposure 

ARIA/RD believes occupational handlers will be exposed to short-term duration exposures (1-30 

days). Multiple applications are generally not expected and treatment plots are expected be rather 

small by comparison to typical, large acreage row crops. Private (i.e., grower) applicators may 

perform all functions, that is, mix, load and apply the material. Standard HED practice directs that 

although the same individual may perform all those tasks, they shall, in some cases, be assessed 

separately. The estimates of exposure to pesticide handlers are based upon surrogate study data. 

For pesticide handlers, it is HED standard practice to present estimates of dermal exposure for 

“baseline” that is, for workers wearing appropriate work clothing. Since nicosulfuron dermal and 

inhalation risks are based on an endpoint selected from an oral study, default 100% dermal and 

inhalation absorption factors were used in the occupational assessment Since the dermal and 
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inhalation toxicological endpoints were identified from the same study and effects, the dermal and 

inhalation exposures are summed prior to use in calculation of margins of exposure (MOE, where 

MOE = NOAEL ÷ Average Daily Exposure). The estimated MOEs are all > 100, with the most 

exposed occupational population MOE at 3,400. Therefore the proposed Section 18 use does not 

exceed ARIA/RD’s level of concern for pesticide handlers. 

It is possible for agricultural workers to have post-application exposure to pesticide residues during 

the course of typical agricultural activities. Since the requested applications of nicosulfuron are for 

early season (early post-emergence), scouting is expected to be the most likely post-application 

activity. The MOE from nicosulfuron during scouting was calculated using HED’s SOP for 

occupational exposure to be 8,445. Since an MOE of 100 is adequate to protect agricultural 

workers from post-application exposures, risks from the proposed Section 18 use do not exceed 

ARIA/RDs level of concern. 

Regulatory Decision 

There are no data needs at this time for residue chemistry, and occupational and residential 

exposure. However, there are other data requirements listed in Section 10 below. 

To support the proposed Section 18 use on Bermudagrass, ARIA recommends for time-limited 

tolerances for nicosulfuron [3-pyridinecarboxamide, 2-((((4,6-dimethoxypyrimidin-2-

yl)aminocarbonyl) aminosulfonyl))-N,N-dimethyl] in/on: 

Bermudagrass, forage ............................................10 ppm 

Bermudagrass, hay.................................................25 ppm 

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

human health risk assessment, in accordance with U.S. 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). 

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 studies have been determined to 

require a review of their ethical conduct, and have received that review. 

2.0 Ingredient Profile

Nicosulfuron is a member of the sulfonylurea family of herbicides which includes, among others, 

halosulfuron, pirimisulfuron and chlorsulfuron. Nicosulfuron is used for control of weeds such as 

Johnsongrass, quackgrass, foxtails, shattercane, panicums, barnyardgrass, sandbur, pigweed, 

morning glory and others. Nicosulfuron’s herbicidal action is due to the inhibition of the enzyme 

acetolactate synthetase leading to the disruption of cell division and plant growth. The registered 

formulations of nicosulfuron include water dispersible granules, an emulsifiable concentrate, and 

suspension concentrates. 

2.1 Summary of Proposed Uses 

The registrant, DuPont Crop Protection, in support of the Section 18 requests from Oklahoma 

Department of Agriculture, Food, and Forestry and the Texas Department of Agriculture provided 

a copy of a label for PastoraTM Herbicide (EPA Reg. No. not registered, 3.19 lb ai/gal DF). The 

proposed new use is summarized below in Table 2.1. 
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Table 2.1. Summary of Directions for Use of Nicosulfuron. 

Applic. Timing; 

Type; and 

Equip. 

Formulation 

[EPA Reg. 

No.] 

Applic. Rate 

(lb ai/A) 

Max. No. 

Applic. 

per 

Season 

Max. 

Seasonal 

Applic. Rate 

(lb ai/A) 

PHI 

(days)

Use Directions and 

Limitations 

Bermudagrass 

Broadcast foliar; 

Ground or aerial 

equipment 

3.19 lb/gal 

DF 

[not 

registered] 

0.035-0.053 

(1.0-1.5 oz 

formulation) 

2 

0.088 

(2.5 oz 

formulation) 

0 

Use of a spray adjuvant is 

required. Apply only to 

established Bermudagrass 

that is at least one year old.

The proposed use directions are adequate to allow evaluation of the residue data relative to the 

proposed use. 

2.2 Structure and Nomenclature

The structure and nomenclature of nicosulfuron are summarized in Table 2.2. 

Table 2.2 Nicosulfuron Nomenclature

Chemical structure 

N

N

O

CH3

CH3

S

N

O

O H N

O

H N

N

OMe

OMe

Empirical Formula C15H18N6O6S 

Common name nicosulfuron 

IUPAC name 2-(4,6-dimethoxypyrimidin-2-ylcarbamoylsulfamoyl)-N,Ndimethylnicotinamide; 1-(4,6-dimethoxypyrimidin-2-yl)-3-(3-

dimethylcarbamoyl-2-pyridylsulfonyl)urea 

CAS name 2-[[(4,6-dimethoxypyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-N,Ndimethyl-3-pyridinecarboxamide 

CAS # 111991-09-4 

End-use product/EP ACCENT, CELEBRITY, and STEADFAST 

Chemical Class sulfonylureas 

 

2.3 Physical and Chemical Properties

Nicosulfuron’s physical and chemical properties are summarized below in Table 2.3. 

Table 2.3 Physicochemical Properties of Nicosulfuron

Parameter Value Reference 

Molecular Weight 410.4 
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Table 2.3 Physicochemical Properties of Nicosulfuron

Parameter Value Reference 

Melting point/range 141-144°C 40954501, 40924203 

pH A slurry in HPLC water caused pH to decrease 

from 6.6 to 4.5 

40954501, 40924203 

Density 0.313 g/mL 40954501, 40924203 

Water solubility @ 25°C: 0.04 g/100g pH=5.0; 1.2 g/100g 

pH=7.0; 3.9 g/100g pH=9.0 

40954501, 40924203 

Solvent solubility 28oC: acetone, 0.018 ppm; acetonitrile, 0.023 

ppm; benzene, 0.003; chloroform, 0.064 ppm; 

DMF, 0.064 ppm; ethanol, 0.004 ppm; 

methylene chloride, 0.160 ppm 

40954501, 40924203 

Vapor pressure 1.2 x 10-16 torr at 25°C 40954501, 40924203 

Dissociation constant, pKa 4.3 (acid) 40954501, 40924203 

Octanol/water partition 

coefficient, Log(KOW) 

@ 25°C: 0.44 (pH 5); 0.017 (pH 7); 0.01 (pH 9) 40954501, 40924203 

UV/visible absorption spectrum not available data outstanding 

3.0 Hazard Characterization/Assessment 

3.1 Hazard Characterization

For a more detailed characterization of the toxicity/dose response of nicosulfuron, selection of 

endpoints and FQPA, please refer to the human health risk assessment conducted for the 

Reregistration Eligibility Decision Document (RED) (D301619, November 19, 2004). No new 

toxicity data have been submitted since the RED. Toxicity profile tables summarizing the database 

are provided in Appendix A. Although additional studies (rat acute and subchronic neurotoxicity; 

rat 21-day dermal; and immunotoxicity studies) are required under the current (revised) 40 CFR 

Part 158 toxicity data guidelines, the existing database is considered adequate for purposes of 

assessing human health risk from this emergency exemption use. 

Nicosulfuron is a member of the sulfonylurea family of herbicides. Its herbicidal action is due to 

the inhibition of acetolactate synthetase, leading to the disruption of cell division and elongation in 

the plant. This mode of herbicidal action is not relevant to human toxicity as acetolactate 

synthetase does not occur in humans or animals. 

Nicosulfuron is of low toxicity in animals by all routes and durations of exposure. It is of minimal 

or low toxicity (category III or IV) in the 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 increase in the relative liver and kidney 

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

comparable dietary levels. No dermal or inhalation studies were submitted. 

No developmental or reproductive effects were observed in rats, but in rabbits, maternal toxicity 

(clinical signs, decreased body weight gain during dosing, increased abortions), postimplantation 

loss and decreases in fetal body weight were observed. Toxicity to the fetus was only observed at 

maternally toxic doses. There were no indications of neurotoxic or immunotoxic effects. 

Nicosulfuron is not likely to be carcinogenic based on bioassays in the rat and mouse and lack of 

effects in the in vitro and in vivo genotoxicity studies. 
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Upon oral administration, nicosulfuron is poorly absorbed. In the rat, most of the administered 

dose was excreted as unmetabolized parent compound, primarily via the feces (total fecal excretion 

80-95%) and a lower percentage was excreted in the urine (total urinary excretion 9-20%). 

Radioactivity was not retained in tissues at significant levels. Minor metabolites of hydrolytic and 

oxidative metabolism were identified. The poor absorption is consistent with the low toxicity 

observed in the available studies. 

3.2 Dose-Response 

Due to the lack of observed effects in the database as a whole, the studies suitable for selection of 

endpoints for risk assessment were limited to the rabbit developmental study and the dog chronic 

study. Maternal effects in the rabbit developmental study consisted of vaginal discharge, staining 

of hair in the rectal and vaginal areas, decreased body weight gain during the dosing period and 

late abortion. An increase in percentage postimplantation loss was observed at 500 mg/kg/day and 

decreased fetal body weight was observed at 1000 mg/kg/day. The NOAEL was 100 mg/kg/day. 

Effects in the chronic dog study were limited to decreased body weight gain in males and increases 

in liver and kidney weight at the LOAEL of 500 mg/kg/day with a NOAEL of 125 mg/kg/day. 

Although these two oral studies were of different dosing durations, they had similar NOAELs and 

LOAELs. The slight difference in NOAELs (125 vs.100 mg/kg/day) is a result of dose-spacing 

rather than actual differences in toxicity, and the LOAELs for each study (both 500 mg/kg/day) 

were significantly higher than the NOAELs. The dog chronic study NOAEL of 125 mg/kg/day 

was selected for all risk assessment scenarios of all exposure routes and durations as a more 

realistic NOAEL, supported by the rabbit developmental toxicity study. It is considered protective 

of potential pre- and/or postnatal toxicity based on observation of developmental effects in the 

rabbit at a much higher LOAEL (500 mg/kg/day). Each exposure scenario is discussed as follows: 

Acute Dietary Endpoint: No effects were considered attributable to a single day’s exposure; 

therefore, an assessment was not performed. 

Chronic Dietary Endpoint (all populations): The NOAEL of 125 mg/kg/day from the chronic dog 

study was selected, where decreased body weight gain in males and increased relative liver and 

kidney weights were observed at the LOAEL of 500 mg/kg/day. The study is of an appropriate 

route and duration for this assessment. The FQPA safety factor is discussed below in Section 3.3. 

Residential Exposure: Endpoints for residential exposure were not selected because there are 

presently no residential uses. 

Short- and Intermediate Term Occupational Dermal and Inhalation: The NOAEL of 125 

mg/kg/day from the dog chronic oral study was selected for all occupational exposure scenarios. 

The rationale for this selection was discussed above. For both dermal and inhalation exposure, a 

default absorption factor of 100% of oral absorption was applied since an oral study was selected 

and dermal/inhalation absorption data were not available. 

Carcinogenicity: Nicosufuron is classified as “not likely to be carcinogenic to humans” based on 

lack of tumorigenic effects in rodent (rats and mice) bioassays at the limit doses and was not 

mutagenic in in vitro and in vivo genotoxicity assays. Therefore there is no cancer risk associated 

with the proposed Section 18 use. 

MOE for Occupational/Residential Risk Assessments: A MOE of 100 (10 x for interspecies 

extrapolation and 10x for intraspecies variation) is adequate. No additional safety factors were 

included to account for lack of studies (neurotoxicity, immunotoxicity) because the database as a 
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whole indicated low toxicity of nicosulfuron and there was no evidence of neurotoxicity or 

immunotoxicity in the available studies; therefore, it is considered unlikely that these studies 

would provide a lower NOAEL for risk assessment. 

3.3 FQPA Considerations and Safety Factor Determination

Reduction of the special FQPA SF to 1x is recommended. The database is adequate for the 

purpose of this Section 18 risk assessment, and developmental toxicity studies in two species and a 

rat multigeneration reproductive toxicity study are available. Nicosulfuron is poorly absorbed and 

toxicity is low in the available studies. No developmental or reproductive effects were observed in 

rats, and developmental toxicity in rabbits (postimplantation loss, decreased fetal body weight) 

was observed only in the presence of maternal toxicity. Abortions and postimplantation loss were 

observed at the maternal toxicity LOAEL, along with clinical signs and decreased body weight 

gain. Increased pre- and/or postnatal susceptibility was not observed and there was no evidence of 

neurotoxicity or immunotoxicity. There are no residential uses and exposure assessments will not 

underestimate risks. There are no concerns and no residual uncertainties with regard to assessment 

of pre- and/or postnatal toxicity. 

3.4 Hazard Identification and Toxicity Endpoint Selection

3.4.1 Level of Concern for Margin of Exposure

Table 3.4.1. Summary of Levels of Concern for Risk Assessment. 

Route 

Short-Term 

(1 - 30 Days) 

Intermediate-Term 

(1 - 6 Months) 

Long-Term 

(> 6 Months) 

Occupational (Worker) Exposure

Dermal 100 100 N/A 

Inhalation 100 100 N/A 

Residential Exposure

Dermal N/A N/A N/A 

Inhalation N/A N/A N/A 

Incidental Oral N/A N/A N/A 

 N/A Not applicable (risk assessment not required due to use patterns) 

3.4.2 Recommendation for Aggregate Exposure Risk Assessments

The aggregate exposure assessments are only chronic food + drinking water (both surface and 

ground water model estimates).

3.4.3 Summary of Toxicological Doses and Endpoints for Nicosulfuron for Use in Human 

Risk Assessments

Table 3.4.3.a 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 
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Table 3.4.3.a 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 

Oral toxicity – dog 

NOAEL = 125 mg/kg/day based upon 

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 and 

considered this dose to be the LOAEL for 

the test material. 

Supported by the NOAEL of 100 

mg/kg/day/LOAEL 500 mg/kg/day in the 

rabbit developmental toxicity study. 

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). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use 

of a short-term study for long-term risk assessment. UFDB = to account for the absence of key date (i.e., lack of a 

critical study). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = 

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

Table 3.4.3.b 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 (shortand intermediateterm) 

NOAEL=125 

mg/kg/day 

DAF = 100% 

(default) 

UFA= 10x 

UFH= 10x 

Occupational 

LOC for MOE < 

100 

Oral toxicity – dog 

NOAEL = 125 mg/kg/day based upon 

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. 

Supported by the NOAEL of 100 

mg/kg/day/LOAEL 500 mg/kg/day in the 

rabbit developmental toxicity study. 
 12 of 30 

Table 3.4.3.b 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 (shortand intermediateterm) 

NOAEL=125 

mg/kg/day 

IAF = 100% 

(default) 

UFA= 10x 

UFH= 10x 

Occupational 

LOC for MOE < 

100 

Oral toxicity – dog 

NOAEL = 125 mg/kg/day based upon 

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 and 

considered this dose to be the LOAEL for 

the test material. 

Supported by the NOAEL of 100 

mg/kg/day/LOAEL 500 mg/kg/day in the 

rabbit developmental toxicity study. 

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). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use 

of a short-term study for long-term risk assessment. UFDB = to account for the absence of key date (i.e., lack of a 

critical study). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = 

reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable. DAF = dermal 

absorption factor. IAH = Inhalation absorption factor. 

4.0 Public Health and Pesticide Epidemiology Data

No data exists for nicosulfuron in NHANES or AG HEALTH studies. 

5.0 Dietary Exposure/Risk Characterization 

5.1 Pesticide Metabolism and Environmental Degradation

DP Num: 302694, D. Hrdy, 11/30/04 

5.1.1 Metabolism in Primary Crops

Based upon the results of the nicosulfuron metabolism study in corn, the metabolism of 

nicosulfuron proceeds predominantly via two mechanisms: the hydrolysis of the sulfonylurea 

bridge yielding pyridine sulfonamide and pyrimidine amine, and the hydroxylation of nicosulfuron 

at the 5-position of the pyrimidine amine followed by glucosidation (in early forage samples). The 

glucose conjugate and its aglycone were present in the whole plant, but were not present in the 

fodder or stover (113 day PHI). The grain and cob were not analyzed since these contained <0.005 

ppm total 14C-equivalents of nicosulfuron. Pyridine sulfonamide was present in the whole plant 

and in silage, and fodder and stover The analyses show that nicosulfuron gradually decreases 

during the corn growing season and is present in very low levels at maturity. However, residues of 

metabolite pyridine sulfonamide begin at day 0 and are detected in the whole plant and stalk at 

maturity. These residues are higher than the detected residues of the nicosulfuron. Pyrimidine 

amine is further metabolized to 5-OH pyrimidine amine and its glucoside, but is not detected in the 

whole plant or in fodder or stover. 

5.1.2 Metabolism in Rotational Crops
 13 of 30 

The submitted confined rotational crop studies are acceptable. Based upon the data there is 

indication that metabolites /degradates containing the pyridine ring are more readily taken up by 

plants than those containing the pyrimidine ring. Neither in soils nor in plants were the pyrimidine 

amine residues detected even though this metabolite is a major metabolite/degradate of 

nicosulfuron. Maximum total residues were observed in soybean forage/hay and seeds when the 

pyridine labeled material was used, but the amount of residues decreased with the aging period of 

the soil. The major metabolite detected was pyridine sulfonamide. With the pyrimidine labeled 

material, total residues were lower and the only identified metabolite/degradate was N-desmethyl 

nicosulfuron, which was higher in forage/hay than in seeds. Maximum total residues were also 

observed in wheat straw/chaff when the pyridine labeled nicosulfuron was used; pyridine 

sulfonamide was the major metabolite/degradate identified. The lowest residues were identified in 

lettuce leaves and radish roots. (Accession #: 412004-044, E. Regelman, 6/1/90). 

5.1.3 Metabolism in Livestock

In studies in which lactating goats were treated with radiolabeled nicosulfuron for 3 consecutive 

days, residues continued to increase in the milk up to day 3 for the pyrimidinyl-labeled 

nicosulfuron and then apparently plateaued, while the pyridinyl-labeled nicosulfuron gave no 

detectable 14C-residues on day 1, 2, or 3. The total 14C activity measured in milk (pyrimidinyllabeled) was a maximum of 0.03 ppm (0.03% total radioactive residue, TRR). The administered 

14C-dosage was excreted in the urine at 46% and 17%, and in the feces at 62% and 32%, 

respectively for the pyridinyl- and pyrimidinyl-labeled nicosulfuron. Uptake of residues was low 

for all tissues and organs for either label. The highest level, 0.1 ppm (0.04% of total dose) was in 

the liver from the goat treated with the pyridinyl label. All other tissues had TRR of 

approximately 0.07 ppm or less (nicosulfuron equivalents). Radioactivity in the collected bile 

comprised 0.1% and 0.7% of the total dose, respectively for the pyridinyl- and pyrimidinyl labeled 

nicosulfuron. 

The proposed metabolic pathway for nicosulfuron in the goat showed primarily three mechanisms: 

1) hydrolysis of the sulfonylurea bridge to yield pyridine sulfonamide and pyrimidine amine (both 

of which undergo additional metabolism); 2) N-demethylation and subsequent loss of sulfur 

dioxide leading to the cyclized compound was identified as a “cyclized ipso compound,”; and 3) 

oxidation and conjugation at the 5-position of the pyrimidine ring. 

A poultry metabolism study was not required (R. Schmitt, 7/25/89) because at the proposed 

treatment rates the RACs used for feeding poultry, would contain no detectable residues of 

nicosulfuron (<0.05 ppm), or any significant metabolites as evidenced by the plant metabolism 

study. 

5.1.4 Analytical Methodology 

90-TN-03, A. Akins, 1/11/90 

PP#7G3564, F. Suhre, 1/30/89 

CIBA-Geigy’s method, AG-499, an HPLC/UV method, was found adequate for enforcement 

purposes. The procedure has a LOD of 0.05 ppm. The method was recommended for inclusion in 

the Pesticide Analytical Manual Vol. II (PAM II). The method is adequate for enfocement of the 

Section 18 time-limited tolerance. 

Grass forage and hay samples in the administrative materials submitted by DuPont in support of 

the Section 18 request were analyzed for nicosulfuron using procedures described in DuPont17928, dated May 26, 2006, entitled "Analytical Method for the Determination of Nicosulfuron 

(DPX-V9360) and its Metabolite IN-V9367 in Pasture Grass by HPLC/ESI-MS/MS" including 
 14 of 30 

modifications to the method dated December 20, 2007 and deviations to the method dated January 

28, 2008, January 31, 2008, and March 14, 2008. Residues found in/on samples are reported as 

nicosulfuron, IN-V9367 (expressed as nicosulfuron parent equivalents), and total nicosulfuron 

parent equivalents, based upon the molecular weight mathematical conversion. 

Briefly, residues of nicosulfuron and IN-V9367 were extracted from fortified grass samples by 

homogenization in acetone: 0.1M ammonium carbonate (90:10, v/v) followed by shaking in 0.1 M 

ammonium carbonate. Aliquots of the sample extracts were purified by solid phase extraction 

(SPE). The compounds were eluted from the cartridges with methanol. The eluates were 

evaporated to dryness under a gentle stream of nitrogen gas at 35°C and then reconstituted in 

methanol: 10mM ammonium formate (5:95, v/v) solution and filtered. The purified extracts were 

analyzed by reversed-phase HPLC with electrospray mass spectrometry/mass spectrometry (ESIMS/MS) for detection. The method LOD and LOQ were 0.003 mg/kg and 0.010 mg/kg, 

respectively. 

Morse Laboratories, Inc. of Sacramento, California, conducted a successful ILV of the Analytical 

Method “Analytical Method for the Determination of Nicosulfuron (DPX-V9360) and its 

Metabolite IN-V9367 in Pasture Grass by HPLC/ESI-MS/MS, DuPont-17928.” The study reports 

of this analytical method and validation (DuPont-17928 and DuPont-18853) will be submitted with 

the tolerance petition. 

The description of the method used for data gathering is included for informational purposes. The 

adequacy of the method will be assessed when submitted with the tolerance petition. 

5.1.5 Environmental Degradation 

The primary degradation pathways were hydrolysis and oxidation. Nicosulfuron hydrolyzed to the 

major transformation product V9367 (pyridine sulfonamide) and to o-desmethyl nicosulfuron 

(37740), and then further degraded to the unidentified major transformation product “metabolite 

A,” which has the sulfonylurea bridge intact. 

The major transformation products detected in the soil were pyridine sulfonamide and the 

unidentified “metabolite A”. Pyridine sulfonamide was detected in the 0-6 inch soil depth at a 

maximum concentration of 0.004 ppm at 121 days and decreased to 0.001 ppm by 366-548 days 

posttreatment. Pyridine sulfonamide was not detected in the 6-12 inch soil depth above 0.001 

ppm. “Metabolite A” was detected in the 0-6 inch soil depth at a maximum concentration of 0.004 

ppm at 250 days and decreased to 0.003 ppm by 366-548 days posttreatment. “Metabolite A” was 

detected in the 6-12 inch soil depth at a maximum of 0.002 ppm at 366 days posttreatment. 

The only major transformation product detected in the soil treated with [pyrimidine-2-

14C]nicosulfuron was the unidentified “metabolite A”, which was detected in the 0-6 inch soil 

depth at a maximum concentration of 0.004 ppm at 121 and 250 days, and decreased to 0.003 ppm 

by 456-548 days posttreatment. “Metabolite A” was not detected in the 6-12 inch soil depth above 

0.001 ppm. 

In lysimeters treated with [pyridine-2-14C] nicosulfuron, material balances decreased from 84.6-

87.5% at 0-121 days to 72.9-75.6% by 250-548 days following treatment. In lysimeters treated 

with [pyrimidine-2-14C] nicosulfuron, material balances decreased from 76.7-92.2% at 0-121 days 

to 70.7-71.8% by 250-366 days and 53.6% by 548 days following treatment. The study authors 

attributed losses of radioactivity from lysimeters treated with both labels to the production of a 

volatile compound that was not captured. For the purposes of this Section 18, the residue of 
 15 of 30 

concern in drinking water is nicosulfuron only. 

5.1.6 Comparative Metabolic Profile 

The metabolism of 14C-nicosulfuron was studied in male and female rats. Following oral dosing, 

most of the radioactivity was excreted unchanged within 24 hours. Elimination in the feces 

accounted for 80 to 95% of the dose, and elimination in the urine accounted for 9 to 20%. 

Elimination of 14CO2 was negligible (<0.01 of the administered dose). Following intravenous 

administration, approximately 76 to 80% of the dose was eliminated in the urine and 27 to 30% in 

the feces. Residues in tissues accounted for 0.05 to 0.5% of the dose. The major excretion product 

in urine and feces was unchanged parent compound. In addition, pyridinesulfonamide (N, Ndimethyl-2-sulfonamide pyridine-3-carboxamide) was detected in the urine and accounted for 1.1 

to 5.7% of the dose. Pyridine acid sulfonamide (2-sulfonamidepyridine-3-carboxylic acid) was 

tentatively identified as a minor metabolite in the feces of orally dosed rats and urine of 

intravenously dosed rats. These metabolites represent hydrolytic cleavage/oxidation of the parent 

molecule. 

The metabolic pathway of nicosulfuron in plants is similar to its pathway in rats. Based upon the 

results of the nicosulfuron metabolism study in corn, the metabolism of nicosulfuron proceeds 

predominantly via two mechanisms: the hydrolysis of the sulfonylurea bridge yielding pyridine 

sulfonamide and pyrimidine amine, and the hydroxylation of nicosulfuron at the 5-position of the 

pyrimidine amine followed by glucosidation (in early forage samples). The analyses show that 

nicosulfuron gradually decreases during the corn growing season and is present in very low levels 

at maturity. However, residues of metabolite pyridine sulfonamide begin at day 0 and are detected 

in the whole plant and stalk at maturity (113 day PHI) exceeding residues of nicosulfuron. 

Pyrimidine amine is further metabolized to its 5-hydroxy derivative and its glucoside, but is not 

detected in the whole plant (49 day PHI) or in fodder or stover (113 day PHI). 

The metabolic pathway of nicosulfuron in livestock also appears to be similar to the rat and plant. 

The likely metabolic pathway for nicosulfuron in livestock is hydrolysis of the sulfonylurea bridge 

to yield pyridine sulfonamide and pyrimidine amine (both of which undergo additional 

metabolism), N-demethylation and subsequent loss of sulfur dioxide leading to an unidentified 

cyclized compound; and oxidation and conjugation at the 5-position of the pyrimidine ring. 

5.1.7 Pesticide Metabolites and Degradates of Concern 

Table 5.1.7. Summary of Metabolites and Degradates to be included in the Risk Assessment 

and Tolerance Expression

Matrix Residues included in Risk 

Assessment 

Residues included in 

Tolerance Expression 

Plants Primary Crop Nicosulfuron Nicosulfuron 

Rotational Crop Nicosulfuron Nicosulfuron 

Livestock Ruminant Not Applicable Not Applicable 

Poultry Not Applicable Not Applicable 

Drinking Water Nicosulfuron Not Applicable 

5.1.8 Drinking Water Residue Profile

DP Num: 301842, 302623, 302624, L. Liu, 7/28/04 
Page 16 of 30 

EFED presented the Tier I EECs for nicosulfuron, estimated using the models FIRST for surface 

water and SCIGROW for groundwater in the human health risk assessment. 

For nicosulfuron, the surface water the chronic (average 56-day) value is 0.685 ppb based on the 

application on corn. The groundwater screening concentration is 0.056 ppb for nicosulfuron. 

The highest result of the two models, surface water at 0.685 ppb, should be used for water, all 

sources (both indirect and direct). The water model estimates were placed in all water food 

forms, both indirect and direct, for the aggregate food + water assessment. 

Table 5.1.8. Summary of Estimated Surface and Ground Water Concentrations for Nicosulfuron.

Exposure Duration

Surface Water Conc., ppb a Ground Water Conc., ppb b

Chronic (non-cancer) 0.685 ppb 0.056 ppb

Chronic (cancer) N/A N/A 

a

 From the Tier I FIRST 

b

 From the SCI-GROW model 

5.1.9 Food Residue Profile

In support of the proposed Section 18 use, the Dept. of Agriculture has cited a volume of 

administrative materials for an upcoming petition entitled “Petition for Establishment of 

Tolerances for Nicosulfuron on Grass Forage, Grass Hay, Meat, Meat by-products, Milk and 

Milk, fat,” (R. Ashley, 12/2008). Thirteen residue field trials were conducted on Bermudagrass, 

brome, and fescue in Regions 5 (Eastern ND and NE and Central MO and IA), 6 (Eastern TX 

and OK), 7 (Central SD), and 8 (Western TX and OK). Nicosulfuron 75WG was applied either 

as a single foliar broadcast application at the rate of 1.41 oz ai/A (0.088 lb ai/A), or as two foliar 

broadcast applications at the target rates of 0.938 oz ai/A (0.059 lb ai/A) and 0.469 oz ai/A 

(0.029 lb ai/A). Non-ionic surfactants or nitrogen were included in the spray mixture in all 

applications. 

Samples were harvested the same day as the last application (email, S. Groce, 3/31/09). Forage 

samples were cut at the same time as the hay samples, but were immediately frozen without 

drying. Analysis of the samples was conducted using the method described in DuPont-17928. 

The registrant reported that the LOQ of the analytical method was 0.010 ppm and the LOD was 

0.003 ppm (1/3 the LOQ). Nicosulfuron residues in grass forage ranged from 0.032 ppm to 7.7 

ppm. Nicosulfuron residues in grass hay ranged from 0.11 ppm to 18.0 ppm. 

Table 5.1.9.a Summary of Crisis Exemption Use 

Patterns. 

State OK TX 

Application Dates April 1,2009 Early February 

2009 

Counties Throughout state 
Page 17 of 30 

Table 5.1.9.a Summary of Crisis Exemption Use 

Patterns. 

State OK TX 

Crop Bermudagrass 

Pest Sand bur 

Formulation PastoriaTM 

# of Applications 2 

Max. Appl. Rate 1.0-2.5 fl oz (0.035-0.088 lb ai) 

/A/yr 

Acreage 200K 11,200K 

Application Interval NA 

Pre-harvest Interval Harvest or grazing may begin at 

any time. 

Other Apply only to established 

Bermudagrass that is at least one 

year old. 

These data indicate that a time-limited tolerance for nicosulfuron residues on Bermudagrass, 

forage should be established at 10 ppm and on Bermudagrass, hay at 25 ppm. 

Grass forage and hay are feed items for beef and dairy cattle. Table 5.1.9.b, below, shows a 

reasonably balanced dietary burden for cattle using the established tolerances for corn 

commodities as well as the proposed time-limited tolerances for Bermudagrass (e-mail, J. 

Stokes, 4/6/09). The diet results in an exposure of 3.0 ppm for both beef cattle and 5.8 ppm for 

dairy cattle. Previously submitted metabolism studies using lactating goats dosed with either 

[pyrimidine 2-14C] nicosulfuron or [pyridine-2-14C] nicosulfuron at a daily feeding level of 

approximately 60 ppm showed uptake of residues was low for all tissues and organs for either 

label. The highest level found, 0.1 ppm (0.04% of total dose), was in the liver from the goat 

treated with the pyridinyl label. All other tissues had TRR of approximately 0.07 ppm or less 

(MRID 41082627). Using the dietary burden and the dosage and results of the metabolism 

study, residues would not be detectable in cattle commodities (0.1 ppm found in liver x 3.0 ppm 

beef cattle diet/ 60 ppm dose = 0.005 ppm in liver). Therefore, ARIA/RD has concluded that as 

a result of this Section 18 use, there would be no detectable residues of nicosulfuron in 

ruminants. 
Page 18 of 30 

Table 5.1.9.b Calculation of Reasonably Balanced Dietary Burdens of Nicosulfuron Residues for Livestock.

Feedstuff Type 1 % Dry 

Matter 2 % Diet 2

 Tolerance (ppm) Dietary Contribution 

(ppm) 3

Beef Cattle R 15%, CC 80%, PC 5%

Bermudagrass, hay R 88 10 25 2.84 

Corn, forage/silage R 40 5 0.1 0.013 

Corn, field, grain/milled byproducts CC 88 80 0.1 0.091 

Untreated PC -- 5 -- -- 

TOTAL BURDEN 100 3.0 

Dairy Cattle R 45%, CC 45%, PC 10%

Bermudagrass, hay R 88 20 25 5.68 

Corn, forage/silage R 40 25 0.1 0.063 

Corn, field, grain/milled byproducts CC 88 45 0.1 0.051 

Untreated PC -- 5 -- -- 

TOTAL BURDEN 100 5.8 1

 R: Roughage; CC: Carbohydrate concentrate; PC: Protein concentrate. 

2

 Table 1 Feedstuffs (June 2008). 

3

 Contribution = ([tolerance /% DM] X % diet). 

Grass feed items are not used for swine and poultry. Since the addition of grass feed items will 

not affect the swine or poultry diets, no change will be required in the associated tolerances (i.e., 

ARIA continues to conclude that livestock tolerances are not needed for the existing use on corn 

or for the proposed Section 18 use on Bermudagrass.. 

5.1.10 International Residue Limits

Codex Alimentarius Commission, Canada, or Mexico have not established maximum residue 

limits (MRLs) for residues of nicosulfuron in/on grasses. Tolerance harmonization is not an 

issue for this petition. 

5.2 Dietary Exposure and Risk

5.2.1 Acute Dietary Exposure/Risk

Since no acute end point has been selected for nicosulfuron, an acute dietary exposure 

assessment was not conducted. 

5.2.2 Chronic Dietary Exposure/Risk

Chronic dietary exposure is determined from food and drinking water. In the case of this Section 

18 request, there are no human food items of regulable interest for Bermudagrass. ARIA has 

also determined that there will be no detectable nicosulfuron residues in livestock commodities. 

A previous chronic dietary (food + water) risk assessment was conducted for the general U.S. 

population and various population subgroups. Drinking water was incorporated directly into the 

dietary assessment using the chronic (annual average) concentration for surface water. The 
Page 19 of 30 

results of the chronic dietary exposure analysis are reported in Table 5.2.3. Tolerance level 

residues were used, assuming 100 %CT, and a single point estimate for drinking water, resulting 

in a conservative analysis for this chronic exposure and risk assessment on nicosulfuron. The 

results indicate chronic dietary risks are below HED’s level of concern (100% cPAD). The 

cPAD value for the general U.S. population is less than 1%, and the %cPAD for the most highly 

exposed population subgroup, children 3-5, is also less than 1% (DP Num: 302694, D. Hrdy, 

11/30/04). 

. 

5.2.3 Cancer Dietary Risk

There is no cancer risk associated with the proposed Section 18 use because nicosulfuron has 

been classified “not likely to be carcinogenic to humans.” 

Table 5.2.3. Dietary (Food +Drinking Water) Exposure and Risk Estimates for Nicosulfuron.

Population Subgroup Acute Chronic Cancer

Exposure

mg/kg/day

%aPAD, Exposure 

mg/kg/day

%cPAD Exposure 

mg/kg/day

Risk

U.S. Population 0.000221 <1 

All infants (< 1 yr) 0.000323 <1 

Children 1-2 yrs 0.000443 <1 

Children 3-5 yrs 0.000506 <1 

Children 6-12 yrs 0.000384 <1 

Youth 13-19 yrs 0.000292 <1 

Adults 20-49 yrs 0.000181 <1 

Adults 50+ yrs 0.000110 <1 

Females 13-49 yrs 

NA NA 

0.000181 <1 

NA NA 

5.3 Anticipated Residue and Percent Crop Treated (%CT) Information

Tolerance level residues and 100%CT were assumed for all registered and proposed 

commodities in the chronic assessment. 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are no residential uses of nicosulfuron; therefore a residential risk assessment was not 

conducted. 

6.1 Other (Spray Drift, etc.)

Spray drift is always a potential source of exposure to residents nearby to spraying operations. 

This is particularly the case with aerial application, but, to a lesser extent, could also be a 

potential source of exposure from the ground application method employed for nicosulfuron. 

The Agency has been working with the Spray Drift Task Force, EPA Regional Offices and State 
Page 20 of 30 

Lead Agencies for pesticide regulation and other parties to develop the best spray drift 

management practices. On a chemical by chemical basis, the Agency is now requiring interim 

mitigation measures for aerial applications that must be placed on product labels/labeling. The 

Agency has completed its evaluation of the new database submitted by the Spray Drift Task 

Force, a membership of U.S. pesticide registrants, and is developing a policy on how to 

appropriately apply the data and the AgDRIFT computer model to its risk assessments for 

pesticides applied by air, orchard airblast and ground hydraulic methods. After the policy is in 

place, the Agency may impose further refinements in spray drift management practices to reduce 

off-target drift with specific products with significant risks associated with drift. 

7.0 Aggregate Risk Assessments and Risk Characterization 

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

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

acute exposure and it has been determined to be a “not likely” carcinogen; therefore there is no 

acute or cancer aggregate risk. ARIA has determined that chronic dietary exposure from food 

and drinking water does not exceed HED’s level of concern (see Section 5.2.2, above). 

8.0 Cumulative Risk Characterization/Assessment

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 tolerance 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 OPP 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/.

9.0 Occupational Exposure/Risk Pathway

DP Num: 361732, M. Dow, 4/1/09 

Based upon the proposed use pattern, ARIA/RD believes the most highly exposed occupational 

pesticide handlers will be 1) mixer/loaders using open-pour loading of dry flowables, 2) 

applicators using open-cab ground-boom sprayers, 3) aerial applicators, 4) applicators using 

ATVs (miniboom or “hand-wand”), 5) mixer/loader/applicators using backpack sprayers, and 6) 

mixer/loader/applicators using hand-held, pump-up sprayers. The latter is not assessed in that 

the assessment of a mixer/loader/applicator using an ATV mounted low-pressure hand-wand 

sprayer is adequate (protective) to describe a hand held sprayer. The spray wands are quite 

similar and the delivery pressures are similar (low pressure). The operator using an ATV 

mounted sprayer is likely more highly exposed than a handler using a pump-up sprayer due to 

the increased area treated per day thus the increased volume handled per day. 
Page 21 of 30 

9.1 Short-Term Handler Risk

ARIA/RD believes occupational handlers will be exposed to short-term duration exposures (1 - 

30 days). Multiple applications are generally not expected and treatment plots are expected be 

rather small by comparison to typical, large acreage row crops. 

Private (i.e., grower) applicators may perform all functions, that is, mix, load and apply the 

material. Standard HED practice directs that although the same individual may perform all those 

tasks, they shall, in some cases, be assessed separately. The available exposure data for 

combined mixer/loader/applicator scenarios are limited in comparison to the monitoring of these 

two activities separately. These exposure scenarios are outlined in the Pesticide Handler 

Exposure Database (PHED) Surrogate Exposure Guide (August 1998). 

HED has adopted a methodology to present the exposure and risk estimates separately for the job 

functions in some scenarios and to present them as combined in other cases. Most exposure 

scenarios for hand-held equipment (such as hand wands, backpack sprayers, and push-type 

granular spreaders) are assessed as a combined job function. With these types of hand held 

operations, all handling activities are assumed to be conducted by the same individual. The 

available PHED and other exposure data support this and HED presents them in this way. 

Conversely, for equipment types such as fixed-wing aircraft, ground-boom tractors, or air-blast 

sprayers, the applicator exposures are assessed and presented separately from those of the mixers 

and loaders. By separating the two job functions, HED/RD determine the most appropriate 

levels of personal protective equipment (PPE) for each aspect of the job without requiring an 

applicator to wear unnecessary PPE that might be required for a mixer/loader (e.g., chemical 

resistant gloves may only be necessary during the pouring of a liquid formulation). 

No chemical specific data were available with which to assess potential exposure to pesticide 

handlers. The estimates of exposure to pesticide handlers are based upon surrogate study data 

available in the PHED (v. 1.1, 1998). For pesticide handlers, it is HED standard practice to 

present estimates of dermal exposure for “baseline” that is, for workers wearing a single layer of 

work clothing consisting of a long-sleeved shirt, long pants, shoes plus socks and no protective 

gloves as well as for “baseline” and the use of protective gloves or other PPE as might be 

necessary. The product label directs applicators and other handlers to wear long-sleeved shirt, 

long pants, shoes plus socks and chemical-resistant gloves in Category A (such as butyl rubber, 

natural rubber, neoprene rubber or nitrile rubber), all ≥ 14 mils. 

Since an oral study was selected fo both dermal and inhalation exposure and risk assessment, 

ARIA assumed default 100% dermal and inhalation absorption factors (relative to oral 

absorption). Since the dermal and toxicological endpoints were identified from the same study 

and effects, the dermal and inhalation exposures were summed prior to use in calculation of 

MOE (NOAEL ÷ Average Daily Exposure). 

Nicosulfuron is not likely to be carcinogenic based on lack of tumurogenic effects in bioassays at 

the limit dose in the rat and mouse and lack of in vitro and in vivo mutagenic effects. 
Page 22 of 30 

Since the adverse effects for all studies utilized in the nicosulfuron risk assessments are not 

gender-specific, the average weight for an adult (i.e., 70 kg) was used to estimate exposure. 

1. Unit Exposures are taken from “PHED SURROGATE EXPOSURE GUIDE”, Estimates of Worker Exposure from The 

Pesticide Handler Exposure Database Version 1.1, August 1998. Dermal = Single Layer Work Clothing No Gloves; Single 

Layer Work Clothing With Gloves; Inhal. = Inhalation. Units = mg ai/pound of active ingredient handled. 

2. Applic. Rate. = Taken from OK and TX section 18 request and from draft label. 

3. Units Treated are taken from “Standard Values for Daily Acres Treated in Agriculture”; ExpoSAC SOP No. 9.1. Revised 5 

July 2000; Area for backpack derived from HED SOP; Area for ATV mounted sprayer is assumed by ARIA/RD. 

4. Average Daily Dose = Unit Exposure * Applic. Rate * Units Treated *100 % dermal absorption ÷ 70 kg Body Weight 

5. MOE = Margin of Exposure = NOAEL ÷ ADD. NOAEL = 125 mg ai/kg bw/day. ADD = dermal + inhalation exposure 

* The unit exposure for M/L/A using an ATV is taken from the PHED for a M/L/A using open 

pour loading of wettable powder and a low-pressure hand-wand sprayer. Typically, ATVs are 

fitted with a spray tank and hand-wand sprayer. “Mini” ground booms are also used. However, 

use of the hand-wand is likely to result in the greatest exposure thus contributes to the most 

conservative (protective) estimate of risk. 5 acres per day is selected as the units treated per day. 

** The unit exposure for a M/L/A using a backpack is based on PHED for open loading of 

liquids. There are no PHED M/L/A data reflecting backpack and dry flowable granules. The 

data for handlers loading liquids are considered to be conservative/protective. The units treated 

are based on the spray volumes recommended. Ground spray volumes vary from 10-30 gpa. 

Table 9.1 Summary of Exposure & Risk to Occupational Handlers From Applying Nicosulfuron to 

Bermudagrass 

Unit Exposure1

mg ai/lb handled 

Applic. Rate2 

lb ai/unit 

Units 

Treated3

Avg. Daily Exposure4

mg ai/kg bw/day 

MOE5

Mixer/Loader - Dry Flowable - Open Pour 

Dermal: 

SLNoGlove 0.066 

SLWithGlove 0.066 

Inhal. 0.00077 

0.0527 

lb ai/A 

350 A/day Dermal: 

SLNoGlove 0.0174 

SLWithGlove 0.0174 

Inhal. 0.0002

No Glove 

7,100 

With Glove 

7,100 

Applicator - Ground-boom - Open-cab

Dermal: 

SLNoGlove 0.014 

SLWithGlove 0.014 

Inhal. 0.00074 

0.0527 

lb ai/A 

200 A/day Dermal: 

SLNoGlove 0.0021 

SLWithGlove 0.0021 

Inhal. 0.00011

No Glove 

57,000 

With Glove 

5,700 

Aerial Applicator (Pilots not required to wear gloves) 

Dermal: 

SLNoGlove 0.005 

Inhal. 0.000068 

0.0527 

lb ai/A 

350 A/day Dermal: 

SLNoGlove 0.00132 

Inhal. 0.000018 

No Glove 

93,000 

Mixer/Loader/Applicator* – ATV low-pressure handwand 

Dermal: 

SLNoGlove no data 

SLWithGlove 8.6 

Inhal. 1.1 

0.0527 

lb ai/A 

5 A/day Dermal: 

no data 

SLWithGlove 0.0324 

Inhal. 0.0041 

With Glove 

3,400 

Mixer/Loader/Applicator** – Backpack sprayer 

Dermal: 

SLNoGlove no data 

SLWithGlove 2.5 

Inhal. 0.03 

0.0527 

lb ai/A 

2 A/day Dermal: 

no data 

SLWithGlove 0.00376 

Inhal. 0.0000452 

With Glove 

33,000 
Page 23 of 30 

Therefore, at a median of 20 gpa spray volume and an Agency default of 40 gallons/day using 

backpack = 2 acres per day. 

A MOE of 100 is adequate to protect occupational pesticide handlers from exposures to 

nicosulfuron. The estimated MOEs are all > 100. Therefore the proposed Section 18 use does 

not exceed ARIA/RD’s level of concern. 

9.2 Short-/Intermediate-/Long-Term Postapplication Risk

It is possible for agricultural workers to have post-application exposure to pesticide residues 

during the course of typical agricultural activities. HED in conjunction with the Agricultural Reentry Task Force (ARTF) has identified a number of post-application agricultural activities that 

may occur and which may result in post-application exposures to pesticide residues. HED has 

also identified transfer coefficients (TC) (cm2/hr) relative to the various activities which express 

the amount of foliar contact over time, during each of the activities identified (HED SOP 003.1, 

Agricultural Transfer Coefficients, Revised August 2000).. 

The HED SOP does not reflect post-application agricultural activity data with regards to 

Bermudagrass. The database does contain information regarding “forage plants.” The highest 

TC listed is 1,100 cm2

/hr for scouting. Since the requested applications of nicosulfuron are for 

early season (early post-emergence), scouting is expected to be the most likely post-application 

activity. 

The small grains crops are also grasses. The highest TC for the small grains is also 1,100 cm2/hr 

for scouting. As a “screening” level assessment, ARIA/RD herein uses the TC of 1,100 cm2

/hr 

for scouting to assess efficacy of the treatment. 

The TCs used in this assessment are from an interim TC SOP developed by HED’s ExpoSAC 

using proprietary data from the ARTF database (SOP # 3.1). It is the intention of HED’s 

ExpoSAC that this SOP will be periodically updated to incorporate additional information about 

agricultural practices in crops and new data on transfer coefficients. Much of this information 

will originate from exposure studies currently being conducted by the ARTF, from further 

analysis of studies already submitted to the Agency, and from studies in the published scientific 

literature.

Lacking compound specific dislodgeable foliar residue (DFR) data, HED assumes 20% of the 

application rate is available as dislodgeable foliar residue on day zero after application. This is 

adapted from the ExpoSAC SOP No. 003 (5/7/98 - Revised 8/7/00). 

The following convention may be used to estimate post-application exposure. 

Average Daily Dose (ADD) (mg ai/kg bw/day) = DFR μg/cm2

 * TC cm2/hr * hr/day * 0.001 

mg/μg * 1/70 kg bw 

 and where: 
Page 24 of 30 

Surrogate Dislodgeable Foliar Residue (DFR) = application rate * 20% available as dislodgeable 

residue * (1-D)t

 * 4.54 x 108 μg/lb * 2.47 x 10-8 A/cm2 . 

0.0527 lb ai/A * 0.20 * (1-0)0 * 4.54 x 108 μg/lb * 2.47 x10-8 A/cm2 = 0.118 μg/cm2

 , therefore, 

0.118 μg/cm2 * 1,100 cm2/hr * 8 hr/day * 0.001 mg/μg ÷ 70 kg bw = 0.0148 mg/kg bw/day. 

MOE = NOAEL ÷ ADD then 125.0 mg/kg bw/day ÷ 0.0148 mg/kg bw/day = 8445.

A MOE of 100 is adequate to protect agricultural workers from post-application exposures. The 

most conservative estimate (i.e., highest exposure/risk) of post-application exposure results in 

MOEs > 100. Therefore, the proposed risk does not exceed ARIA/RDs level of concern. 

10.0 Data Needs and Label Recommendations

ARIA/RD notes that although there are no additional data needed to support the proposed 

Section 18 use on grasses, there are data gaps for toxicology studies which result from the 2007 

update of the Part 158 Data Requirements. The following studies should be submitted in 

support of future Section 3 registrations: 

• Neurotoxicity studies (acute and subchronic) 

• Immunotoxicity study 

• 21/28-day dermal study 

References:

D. Hrdy, 11/30/04, “Nicosulfuron HED Chapter of the Reregistration Eligibility Decision 

Document (RED),” DP Num: 302694 

A. Khasawinah, 11/19/04, “Nicosulfuron - Hazard Characterization Assessment for the 

Reregistration eligiviligiy Decision Document (RED). DP Num D302619. 

D. Hrdy, 11/30/04, “Nicosulfuron Chronic Dietary Exposure Assessment for the Tolerance 

Reassessment Eligibility Decision (TRED),” DP Num: 302621 

Akins, 1/11/90,“90-TN-03. Section 18 Emergency Exemption for the use of Beacon on Field 

Corn to Contol Johnsongrass,” DEB# 6132 

F. Suhre, 1/30/89, PP#7G3564 

E. Regelman, 6/1/90, Accession #: 412004-044 

R. Schmitt, 7/25/89 
Page 25 of 30 

L. Liu, 7/28/04, “Tier I Estimated Environmental Concentrations of Nicosulfuron, for use in 

Human Health Risk Assessment,” DP Num: 301842, 302623, 302624 

M. Dow, 4/1/09, “NICOSULFURON – Human Occupational Exposure/Risk Assessment for the 

Proposed FIFRA Section 18 Use of Nicosulfuron on Bermudagrass Pasture and Hayfields in 

Oklahoma and Texas,” DP Num: 362708 
Page 26 of 30 

Appendix A: Toxicology Assessment

Table A.1 Acute Toxicity Profile - Nicosulfuron

Guideline 

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

870.11 Acute Oral - Rats 

90.6 % ai 

409242054 LD50 > 5000 mg/kg 

Acceptable/Guideline

IV 

870.12 Acute Dermal- Rabbits 90.6% ai 409242074 LD50 = > 2000 mg/kg 

Acceptable/Guideline

III 

870.13 Acute Inhalation - Rats 

90.6% ai 

49242094 LC50 = >5.9 mg/L 

Acceptable/Guideline

IV 

870.24 Acute eye irritation - Rabbits 

90.4% ai 

410826024 Moderate eye irritant 

Acceptable/Guideline

III 

870.25 Acute dermal irritation - 

Rabbits, 90.6 % ai 

410826034 Not irritant 

Supplement/Guideline

IV 

870.26 Skin Sensitization -guinea pigs 

90.4% ai 

410826044 Not a sensitizer 

Acceptable/Guideline

NA 
Page 27 of 30 

Table A.2 Subchronic, Chronic and Other Toxicity Profile: Nicosulfuron

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

870.3100 

90-Day oral toxicity 

(CRL:CD BR rats) 

41082607 (1988) 

Acceptable/guideline 

 (10/sex/dose) at 0, 300, 

1500, 7500 or 20,000 ppm 

94.9% purity

M: 0, 22.2, 107.0, 555.0, 

1495.0 mg/kg/day 

F: 0, 26.0, 133.0, 685.0, 

1830.0 mg/kg/day

NOAEL could not be derived from this study. There was a 

statistically significant decrease (p<0.05) but not in a dose 

dependent fashion in platelets in females at all doses tested both at 

the 45 and 90 day sacrifices. No other hematological parameters 

were significantly affected. Blood calcium and bilirubin were 

significantly depressed (p<0.05) at dose levels of 1500 ppm and 

above in males and females, but not in a dose-dependent fashion. 

Ketones were present in the urine of all treated males in a doserelated manner, but not in females. The hematological and urinary 

findings were not seen in the 24 month study in rats, thus the 

biological significance of these findings in this subchronic test is 

questionable. 

870.3150 

90-Day oral toxicity 

Beagle dogs 

(4/sex/dose)

41082606 (1988) 

Acceptable/guideline 

0, 250, 5000, or 20000 ppm 

94.5% purity 

M: 0, 9.23, 172.0, 710.0 

F: 0, 9.14, 171.0, 683.0 

mg/kg/day

NOAEL is 5000 ppm (172/ 171 mg/kg/day in males/females)

LOAEL = 20,000 ppm (710/ 683 mg/kg/day in males/females) 

based on the hematological finding (reduction of neutrophils in 

females) 

870.3200 

21/28-Day dermal 

toxicity (species) 

None 

870.3250 

90-Day dermal 

toxicity (species) 

None 

870.3465 

90-Day inhalation 

toxicity (species) 

None 

870.3700a 

Prenatal 

developmental in 

(Crl:CD BR mated and 

presumed pregnant 

rats) 

41082608 (1988) 

Acceptable/guideline 

0, 200, 1000 , 2500 or 6000 

mg/kg/day from days 7 

through 16 of gestation.

Maternal NOAEL = 6000 mg/kg/day or greater 

LOAEL = greater than 6000 mg/kg/day 

Developmental NOAEL = 6000 or greater mg/kg/day 

LOAEL = greater than 6000 mg/kg/day. No treatment-related 

effects were noted on maternal or developmental toxicity up to and 

including the highest dose tested of 6 grams/kg (the limit of the 

suspension capability). 

870.3700b 

Prenatal 

developmental in 

(New Zealand White 

SPF Rabbits) 

41082609 (1988) 

Acceptable/guideline 

0, 100, 5000 , 1000 or 2000 

mg/kg/day from days 7 

through 19 of gestation 

Maternal NOAEL = 100 mg/kg/day 

LOAEL = 500 mg/kg/day based on an increase in the number of 

animals with diarrhea (1000 mg/kg/day), possible vaginal 

discharge, abortion, a decrease in body weight gain during the 

dosing period, staining of hair in the rectal and vaginal areas and an 

apparent increase in % postimplantation loss. 

Developmental NOAEL = 100] mg/kg/day 

LOAEL = 500 mg/kg/day based on an apparent increase in percent 

postimplantation loss 

NOAEL for fetal toxicity is 500 mg/kg/day 

LOAEL for fetal toxicity is 1000 mg/kg/day, based on reduced 

mean fetal body weight There were no external on visceral 

anomalies in the fetuses. 
Page 28 of 30 

870.3800 

Reproduction and 

Fertility Effects (rats) 

41360101 (1989) 

Acceptable/guideline 

0, 250, 5000 or 20000 ppm 

M: 14.4-16.7, 289 - 338, 

Parental/Systemic NOAEL = 5000 ppm (287 mg/kg/day) 

LOAEL = 20,000 ppm (1265 mg/kg/day) based on lower body 

weight gain (p<0.05) in the F1 (first mating) females 

NOAEL for reproductive and fetal toxicity = 5000 ppm (287 

mg/kg/day) 

LOAEL = 20,000 ppm (1265 mg/kg/day) based on a statistically 

significant (p<0.05) decrease in litter size at birth and in pup 

weights at postpartum day 14 through 21 in the F2a high dose group. 

870.4300 

Chronic/ 

Carcinogenicity 

(CR:CD-BR Rat) 

41360104 (1989) 

Acceptable/guideline 

(90.6% - 92.8% ai) 

0, 50, 1500, 7500 or 20000 

ppm 

M: 1.9, 58, 289, 786 

F: 2.6, 77, 382, 1098 

mg/kg/day 

NOAEL = 20,000 ppm (786/ 1098 mg/kg/day in males/females, 

highest dose tested). 

LOAEL = >20,000 ppm (786/ 1098 mg/kg/day in males/ females) 

based on the lack of chronic toxic effects. Although, the MTD was 

not achieved, the material was tested at limit dose levels in both 

sexes. No tumors reported. 

870.4100b 

Chronic toxicity 

(Beagle dog) 

41360102 (1989) 

Acceptable/guideline 

(5/sex/dose/group) 

0, 250, 5000 or 20000 ppm 

M & F : 0, 6.25, 125, 500 

mg/kg/day 

LOAEL = 20,000 ppm (500 mg/kg/day) based upon the statistically 

significant increase in the relative liver and kidney weights of males 

NOAEL = 5000 ppm (125 mg/kg/day) 

870.4300 

Carcinogenicity 

(CRL:CD-1(CR)BR 

mouse) 

41360103 (1989) 

Acceptable/guideline 

(80/sex/dose/group) in the 

diet at 0, 25, 250, 2500 or 

7500 ppm (3.2, 31.4, 314, 

953/ 4.2, 43.0, 420, 1260 

mg/kg/day for 

males/females, based on 

90.6% purity) 

NOAEL = 7500 ppm= (953/1260 mg/kg/day in males/females, the 

highest dose tested). 

LOAEL = >7500 ppm (953/1260 mg/kg/day in males/females) 

based on the lack of systemic toxicity. 

(no) evidence of carcinogenicity

870.5100 

Gene Mutation 

Bacterial reverse 

mutation 

Salmonella 

typhimurium

41082612, 41360124 (1988) 

Acceptable/guideline 

 TA98, TA1535 at 0.1 to 1 

microgram /plate, TA97A at 

0.02 to 0.1 microgram/ plate 

and TA100 at 0.1 to 10 

micrograms/plate with and 

without metabolic activation 

INV-9360-7 was nonmutagenic to these strains at doses reaching 

cytotoxic levels in the presence or absence of metabolic activation. 

870.5300 Cytogenetics 

in vitro CHO/HPRT 

mutation assay 

41082614, 41360123 (1988) 

Acceptable/guideline 

 4, 20, 40, 200 or 465 

microgram/mL with or 

without metabolic activation 

Nicosulfuron was non mutagenic. The maximum concentration 

tested 465 micrograms/mL was the limit of the test compound 

solubility in the test system (HED 007963). 

870.8375 Cytogenetics 41082615, 41368001 (1988) Nicosulfuron was not clastogenic under the conditions of this test. 

870.5395 Cytogenetics 41082616, 41360126 (1988) 

Acceptable/guideline 

 0, 500, 2500 or 5000 mg/kg. A positive control group received 40 

mg/kg of cyclophospahmideIN V9360-27 did not induce a 

clastogenic or aneugenic effect in either sex at any dose or sacrifice 

time (24, 48 or 72 hours post-exposure) 
Page 29 of 30 

870.5550 

Other Effects Un 

scheduled DNA 

synthesis in primary 

rat hepatocytes 

41082613, 42360125 (1988) 

Acceptable/guideline 

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

122, 409 or 470 

micrograms/mL. 90.6% ai 

IN V9360-27 did not cause any DNA damage or inducible repair in 

the rat hepatocytes. The highest concentration selected in this study 

was 470 micrograms/mL dose was the limit of solubility in the test 

system without cytotoxicity (HED 007963). 

870.6200a 

Acute neurotoxicity 

screening battery 

NA 

870.6200b 

Subchronic 

neurotoxicity 

screening battery 

NA 

870.6300 

Developmental 

neurotoxicity 

NA 

870.7485 

Metabolism and 

pharmacokinetics 

(Rat) 

41082617 (1988) 

Acceptable/guideline 

Pyridine-2-C14 Accent orally 

at 10 mg/kg or 1000 mg/kg, 

or at 10 mg/kg following oral 

administration of unlabeled 

Accent at 10 mg/kg/day for 

14 days, and iv at 10 mg/kg. 

Pyrimidine-2-C14 labeled 

Accent orally at 1000 mg/kg. 

Total recovery was 98-109% of AD after 4 days of dosing, mostly 

excreted unchanged within 24 hours. No apparent differences 

between sexes or dose groups, although a slightly greater % of the 

AD was detected in feces of animals receiving the high dose than in 

animals receiving the low dose. Following oral dosing, elimination 

in the feces was 80 to 95% of the dose, and in the urine was 9 to 

20%. Elimination of 14C-CO2 was negligible (<0.01 of the AD). 

The average total cumulative excretion indicated half-lives between 

12 and 24 hours. Following iv administration, ~ 76 to 80% of the 

dose was eliminated in the urine and 27 to 30% in the feces. 

Residues in tissues were 0.05 to 0.5% of the dose. The major 

excretion product in urine and feces was unchanged parent 

compound. In addition, pyridinesulfonamide (n,N-dimethyl-2-

sulfonamide pyridine-3-carboxamide) was detected in the urine (1.1 

to 5.7% of the dose). Pyridine acid sulfonamide (2-

sulfonamidepyridine-3-carboxylic acid) 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. 

870.7600 NA 

Special studies NA 
Page 30 of 30 

 Appendix B: International Residue Status

INTERNATIONAL RESIDUE LIMIT STATUS 

Chemical Name: [3-

pyridinecarboxamide, 2-

((((4,6-dimethoxypyrimidin-2-

yl)aminocarbonyl) 

aminosulfonyl))-N,Ndimethyl] 

Common Name: 

Nicosulfuron 

⁬ Proposed tolerance 

⁬ Reevaluated tolerance 

⁬ Other 

Date: 3/31/2009 

Codex Status (Maximum Residue Limits) U. S. Tolerances 

√No Codex proposal step 6 or above 

⁬No Codex proposal step 6 or above for the crops requested

Petition Numbers: 09OK02 

DP Number: 361732 

Other Identifier: 

Residue definition (step 8/CXL): N/A Reviewer/Branch: W. Cutchin 

Residue definition: Nicosulfuron 

Crop (s) MRL (mg/kg) Crop(s) Tolerance (ppm) 

 Bermudagrass, forage 10 

 Bermudagrass, hay 25 

 

 

 

Limits for Canada Limits for Mexico 

⁬ No Limits 

√ No Limits for the crops requested 

⁬ No Limits 

√ No Limits for the crops requested 

Residue definition: 

2[[[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfonyl]-N,N -

dimethyl-3-pyridinecarboxamide 

Residue definition: nicosulfuron 

Crop(s) MRL (mg/kg) Crop(s) MRL (mg/kg) 

 

Notes/Special Instructions: S. Funk, 04/01/2009. 

Rev. 1998