### 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 asse ssment may be needed pendi ng the evaluation of the submitted toxicology studies

and the re

- evaluation of databases using current policies. O ccupational exposure assessments may need to be reassessed to incorporate current occupational exposure policies, currently registered maximu m 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.

I ntroduction

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

se lected 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 o f 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 requi red 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 request s 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 fo r 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), post

implantation 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, t here were no indications of neurotoxic or immunotoxic

effects.

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

The points of departure ( P o Ds) and toxicity endpoints from the most recent risk assessment ( M

. Doherty

, D 360807

, 10 / 27 /2009) are summarized in Attachment 4, Table s 4 .1 and 4.2. The toxicity endpoints and P o Ds for risk assessment were selected for chronic dietary, and short

- and

i ntermediate

- 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 yield ed 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 assess m ent was conducted. The unrefined c hronic dietary (food and drinki ng 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 w as 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 e stimated drinki ng 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 p pm).

### Page 5 of 21

The chronic dietary (food and drinking water) e xposures 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 datab ase is sufficient to support current tolerances

. For corn, t he nature of the residue in plan t s 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. H owever, additional storage stability studies (860.1380), residue

decline studies (860.1500) and field accumulation in ro tational 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 c hemistry 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 chan ges 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

grass es 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 like ly ” human carcinogen; therefore

neither an acute n or 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 w ere not of concern.

### Page 6 of 21

Conclusions : Unless toxicity endpoints for chronic dietary exposure are changed or acute dietary exposure toxicity endpoints are identi fied 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 a nd 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 t he 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

. Beca use the same study and same PoD were chosen for dermal and inhalation exposure assessments, MOEs and exposures can be aggregated where appropriate. C ombined ( dermal + inhalation )

MOEs for nicosulfuron to registered use sites rang ed from 1,3 00 to 93 ,000 at baseline PPE

.

Attachment 5 provides the occupational handler scenarios for nicosulfuron and w hether 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. P ost

application dermal exposures from contact with treated corn and grass es were estimated . The MOEs for post

- application exposure to the registered use sites of ni cosulfuron ranged from 6,200 to 8,400 and were not of concern. However, new assessments may be needed for post

application scenarios at the highest registered application rate for grasses, and because HED policies have changed, i.e.

, new transfer coeffici ents (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 as sessments. The need for a bystander inhalation risk

assessment for nicosulfuron should be examined during registration review.

Conclusions: There is sufficient information available to assess occup ational exposure

. 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 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 ni cosulfuron, 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, includ ing 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 fr om 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

- tier ed 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. Chemica ls 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 pes ticide 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 pesticid e 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

informat ion 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 He alth 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 Uni ted States from January 1, 2006 through December 14, 2011 for the single chemica l nicosulfuron. In the a ggregate 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 wa rrant further investigation. The Agency will continue to

monitor the incident information . I f a concern is triggered, additional analysis will be included

in the risk assessment.

Tolerance Assessment and International Harmonization

Permanent US toleran ces are established under 40 CFR §180.454 for residues of the herbicide nicosulfuron, 2

- [[[[(4,6

- dimethoxy

- 2

- pyrimidinyl)amino]carbonyl]amino]sulfonyl]

- N

, N

dimethyl

- 3

- pyridinecarboxamide, including its metabolites and degradates, in/on the following

commod ities: 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. T he 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 f or 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, Table s 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 accordin g 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

pe sticide 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 pesti cide. 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 perf ormed 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

- a pplication 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 nico sulfuron 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 concern ing 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 Studie s

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 m any 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 gene ric 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 a pplicable 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 Reference s below, four human health risk assessment s ha ve been conducted for

nicosulfuron between 2004 and 2010

. Provided the submitted neurotoxicity and immunotoxicity data are found to be acceptable, t here 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/ 20 04 Nicosulfuron HED Chapter of the Reregistration Eligibility Decision Document (RED).

A. Parmar D335236 10/18/ 20 07 Nicosulfuron

- Side

- by

- Side Field Trials on Corn using Suspension Concentrate and Water Dispersible Granule Formulations

. W. Cutchin D361732 7/14/ 20 09 Nicosulfuron: Human Health Risk Assessment for Proposed Section 18 Use on Bermudagrass. M. Doherty D360807 10/27/ 20 09 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/ 19 95 Nicosulfuron in/on Sweet Corn Amendments.

A. Parmar D 338945,

D342602 10/18/ 20 07 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/ 20 08 Nicosulfuron. Request for Waiver of Sorghum Metabolism Study, Poultry Metabolism Study and Poultry Feeding Study. M. Doherty D369742 10/15/ 20 09 Nicosulfuron

- Dietary Exposure and Risk Analysis to Evaluate a New Use Request for Grasses.

W. Drew D360897 11/6/ 20 09 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. Do herty D374717 3/2/ 20 10 Nicosulfuron

– Resolution of Analytical Method Deficiencies

Noted in HED Review D360897

. Occupational Residential Exposure M. Crowley D302620 11/17/ 20 04 Nicosulfuron Occupational and Residential Exposure Assessment for the Tolerance Reregistration Eligibility Decision (TRED) Document

for Post 84 Pesticide

. S. Oonnithan D339818 8/14/ 20 07 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/ 20 09 Nicosulfuron

– Human Occupational Exposure/Risk Assessment for the Prop osed 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

, N

dimethyl

- 3

- pyridinecarboxamide

IUPAC name 2

- [ (4,6

- dimethoxypyrimidin

- 2

- ylcarbamoy l ) sulfamoyl ]

- N

, N

dimethylnicotinamide;

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/cm 3 relative 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

### 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, pK

a 4.22 MRID 47632204

Octanol/water partition coefficient, K OW 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 Mexico 1 Codex 2

40 CFR 180.454

Plants/Livestock: nicosulfuron, 3

- Pyridinecarboxamide, 2

- [[[[(4,6

- dimethoxy

- 2

- pyrimidinyl)amino] carbonyl]amino]sulfonyl]

- N,N

dimethyl 2[[[[(4,6

- dimethoxy

- 2

- pyrimidinyl)amino]carbon yl] amino]sulfonyl]

- N,N

dimethyl

- 3

- pyridinecarboxamide None

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

US Canada Mexico 1 Codex 2

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 co b 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 dieta ry exposure assessment ( M. Doherty, D 369742

, 10 / 15 / 20 0 9 ) 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 Non

Occupational Human Health Risk Assessments

Exposure/

Scenario Point of Departure Uncertainty/FQPA

Safety Factors RfD, PAD

,

Level of

Concern for

Risk

Assessment Study and Toxicological Effects

Acute Dietary (All

p opulations, 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 UF A = 10x

UF H = 10x FQPA SF= 1x Chronic RfD =

cPAD = 1.25mg/kg/day One Year Dog

- D ecreased body

weight gain in male s 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 (r ats and mice) bioassays at the limit doses and lack of mutagenic effects in the in vitro

and in vivo genotoxicity assays. Point of Departure (P o D) = A data point or an estimated point that is derived from observed dose

- response data and

used to mark th e 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. UF A = extrapolation from animal to human (interspecies). UF H = 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 End points 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) UF A = 10x

UF H = 10x Occupational

LOC for

MOE < 100 One Year Dog

- D ecreased 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 End points 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) UF A = 10x

UF H = 10x Occupational

LOC for

MOE < 100 One Year Dog

- D ecreased body

weight gain in males and the statistically significant increase in the relative liver and kidney weights of males administered 500 mg/kg/day (LOAE L ).

Cancer (oral, dermal, inhalation) Classification: “Not likely to be Carcinogenic to Humans” based on lack of tumorigenic effects in rodent (rats and mice) bioa ssays at the limit doses and lack of mutagenic effects in the in vitro

and in vivo genotoxicity assays. Point of Departure (P o D) = 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. UF A = extrapolation from animal to human (interspecies). UF H = 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 absorpt ion factor.

### Page 19 of 21

Toxicology Data Requirements

The requirements (40 CFR 158. 50 0) for food uses of nicosulfuron are in Table 4.3. Use of the new guideline numbers does not imply that the new guideline pro tocols 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 Type a Application Method Max Application Rate Scenario Assessed or Covered c

M/L A M/L/A Flagger

Field Corn, Sweet Corn, Pop c orn 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

Bermudagrass b 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

Sorghum e 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/hed gerows, 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 (cm 2 /hr) Scenario Covered or

Assessed a

Forage Plants /Grasses 0.053 Scouting (early season, post

emergence) 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,