### UNITED S TATE S ENVIRONMENTAL PROTECTION AGENCY

M E MORANDUM

D A T E : 

### September 14

, 2015 W AS HIN G TON

, D .C. 20 46 0

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION



### SU BJ EC T: Nico s ulfuron

. 

### Human Health Draft R isk Assessment fo r Registra ti on Rev i ew.

P C C o de: 

### 129008
Deci s ion No

. : 

### 503825
P e titi o n N o. : 

### NA DP Barcode: 

### D427029
Re g i s tration N o s .: 

### NA
Re g ulator y Action: 

### Reg i stra ti o n Rev i ew C a se 

### N o.: 7227 Ri s k Assess ment T y pe: 

### Single Chemical Aggregate TXR 

### No

. : 

### NA CA S 

### No

. : 1 11991-09

- 4 40 C FR : 

### § 

### 180.597 MRID 

### N o

. : NA

FRO M :

THRO U GH:

TO: 

### Minerva Mercado-Feliciano,

# Toxicolog**~** Kristin Rury

, Bio l og i st 

## {1/ I-**a-; ~**  Meheret Neguss i e, Chem i st 

### lte/..c,.ye:f**~v.J ~**  

### Ri s k Assessment Branch III Health Effec ts D i vision (7509 P )

C h ris t i n e O l inge r , C hi ef

# ~~vj 

# i----

Ri s k Assessme n t Branch Ill 

# j:7 (

Hea l t h Effects D i vision (750

M i guel Zava l a, Chemical Review Manage r Kelly Sherman, Ri sk Ma n ager Ri s k Management and Impl e mentation Branch III Pest i cide Re-Regis tr at i o n D ivis i o n (7508 P )

This document evaluates the existing uses of nicosu l furon as part of Registration Rev i ew and

repr ese nts the draft risk assessme n t ( ORA )

. N i cosu l furo n is a s ul fo n yl u rea (SU) h e r b i cide. T h e Agency i s reviewing all the SU h e r bicides jointly under Regist r at i on Review. The endpoints and points of depa r ture (PODs) for n icosulf u ron h ave no t change d si n ce the previous risk assessment (K. Rur y, 040875 6, 06 / 26 / 2014). Some studies used fo r endpoint se l ection h ave conservat i ve No Observed Adverse Effect Leve l / Lowest Observed Adve r se Effect Level (NOAEL/LOAEL) values that have not been u pdated to reflect current standards for eva luat in g toxic i ty s tu d i es. Updates wou l d re s u l t in higher NOAEL/LOAEL values and

, given the current risk picture, would n o t impact the overall fi n dings of the r i sk assessmen t.

### Nicosu lfuron Human Health Risk Assess m e nt DP No. D427029

1. 0

2.0

2 .1

2.2

2.3

3.0

3. 1

3.2

3.3

3.4



### 4.0

5.0

5 .1 

### Tab l e of Co nt ents

Exec uti ve S umm ary

..... ..................... ... . ...... .. ....... . .... . ..... ... ..... . ............................................ 3

I-I ED R ecommen dation s

...................................................................................................... 3

Tolerance Considerations

............................................................................... .. .... ... .... ... .. 3

Use Profile & 

### Anticipated Exposure P a thw ays

................. ... .... ... ..... .. ..... .. ..... . ..... .. .......... 3

Consideration of Env ironment a l .Justice

...... . .......................... .. .. .... .......... ..... . . ..... .. ..... . ... 5

H azard C h aracterizatio n

............................................................ . ..... ... .. . . .. .. .. ..... .. ..... .. ... .... .. 6



### S umm a r y of Tox i co l og ic a l Effects

... ... .. .. .. .. .. .. ...... ... . ... . .. . ... ...... . ..... .. ...... . ..... .. .... .. .......... 6 

### Safety Factor fo r In fa nt s and C hildren (FQPA Safety Facto r )

.. .. ...... . ..... .. ..... . ...... . .......... 6 

### Toxicity Endpoint and Point of D eparture Se lection s

..................................... . .... .... .... .... 6



### E nd oc rin e Di sr uption

................ . ...................................................................................... 7



### Re s idue Che m istry

.... .......... .. ...... . ...... .. ................... . .... .... .. ..... . ...... . ........... . ......................... 8

D ietary Ri s k Assess 1n ent

. .. ..... . ..... . ...... .. ..... ... .. .................. .. ..... .. .. . . ... .. ...... . ......................... 9

Wate r Re s id ue P rofil e

..................... ... .. ... ... . ....... .. .. ...... .. .. .. . .. . . .. . ... . ...... . .. ..... .. ..... ... .......... 9

5.2 Dieta r y ( Food + Water) Exposure Assessme nt..

.. .. .. ......... .. .. ............. .. .... .. .................... I 0

6.0 R es i dential (No n-O ccupatio n a l ) Ex posure / Ri sk C h aracterization

.......................... .......... I 

### 0

6.1 Sp r ay D rift

.. .... ... ..... . ...... .. ............................................................................................... I 0

6 .1.1 Co mbin ed Ri sk Est im a t es From Lawn D epositio n Adjacent to Applica ti ons

........ 12

6

. 2 R es id en ti a l Bystande r Po s t-Appli cat i on I nhalation Ex po s ure

.......... .... ................ .. ....... 1 3

7.0 Aggregate Expos ur e / Ri s k Characterization

... ..... ... ... . ............. .. ..... .. ..... .. ..... .. ... .... . ............ I 

### 3

8.0 Cumulative Expos ure / Ri s k C haract e rization

... ...... .. . ............................................... . .. ....... 14

9.0 O ccupat i onal Exposure / Ri sk C h aracter i za ti on

.. ..... ... . ... . ... . .... . ..... ... .. ..... .. .. .... ... ..... .. ..... .. .. 14

9.1 Occ u patio n a l Handler Expos ur e

...... .. ...... ... . ....... . . .. . ... . ... . ...... . ...... .. .. . .. . .................... ...... 14

9.2 Occupa ti o n a l Po s t-Applic a ti on E xposure

..... . ...... ... ..... . ................................................. 17

l 

### 0

. 0 Public Health and P est i c id e Epidemiology D a t a

............................................................... I 

### 8

I 

### 1.0 R efe rence s

.................................................... .. ... ..... .. ... ..... .. ................................................ 19 

### Appe ndix A. Toxi co l ogy Profile

....... . ... ..... ... .. ..... .. ..................................................................... 2 1

A. I 

### Toxicology Data Requir e ment s

... ..... ........................... ........................................ .......... . 2 1

A.2 Toxicity Pr ofiles

.......... .. ..... .. . ..... . .......... . ....... .. . .................. . ........... . ............................... 22 Append i x B. 

### Diet ary Ex p osure / Ri sk M ode lin g I nput and Output..

.............. . ...... . ............. . ...... . ... 25 Ap p e ndi x C. 

### Ph ys ic a l /C h e mi ca l P ropert i es of Nicosu l furo n and Metabolites

. ........................... 28 Append i x D. Revi e w of Human R esea rch

..... . ...... ... .. ..................................................... .. ..... ... ... 30 Append i x E. 

### Int e rnati o nal H armonization

.................. . ....... . ... .... ...... .. ..... .. .................................. 31 Appendix F. 

### DFR D ata Waiver R a tion a le

................................................................................... 32

Page 

### 2 of 32

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

Page 3 of 32 1.0 Executive Summary

Nicosulfuron (2

- [[[[(4,6

- dimethoxy

- 2

- pyrimidinyl)amino]carbonyl]amino]sulfonyl]

- N

, N

- dimethyl

3

- pyridinecarboxamide) is a systemic herbicide belonging to the sulfo nylurea group of herbicides. It is currently registered for use on field corn, sweet corn, popcorn, and grasses (Bermuda grass, grass forage

, and grass hay). It is also registered for use on sorghum plants in seed propagation fields, and on pastures, rangeland and non

- crop areas. Since the last risk assessment ( K. Rury, D408756, 06/26/2014 ) and the scoping document (K. Rury, D397347, 06/11/20 12 )

, there have been no changes to the nico sulfuron use, hazard, or residue profile

. However, the existing uses have been reevaluated here using updated occupational and dietary exposure assessment methodologies. There are no risk estimate s of concern fo r the existing uses of nicosulfuron

.

2 .0 HED Recommendations

2.1 Tolerance Considerations
Permanent US tolerances are established under 40 CFR §180.454 for residues of the herbicide nicosulfuron, 2

- [[[[(4,6

- dimethoxy

- 2

- pyrimidinyl)amino]carbonyl]amino]sulfonyl]

- N,N

dimethyl

- 3

- pyridinecarboxamide, in/on the following commodities: meat byproducts of cattle, goat, horse, and sheep at 0.05 ppm; the meat and fat of cattle, goat, horse and sheep at 0.01 ppm; milk at 0.01 ppm; corn commodities (field, pop, sweet) at 0.1 ppm; grass, forage at 9.0 ppm; and grass, hay at 25.0 ppm. The tolerance expressio n under 40 CFR §180.454 is correct and reflects measurement and compliance of nicosulfuron residues. Since the Section 18 tolerances in §180.454 (b) have expired, HED recommends they be revoke d

. Compliance with the tolerance levels is to be determined by measuring only nicosulfuron. A new use has been proposed on sorghum ( 78 FR 43115 , 7/19/2013 ) and HED has completed a risk assessment for that use (K. Rury, D408756, 06/26/2014) ; however the use has not been registered as of the completion of the current document. Tolerances are recommended for residues in sorghum grain at 0.8 ppm, sorghum forage at 0.3, and sorghum stover at 0. 05 ppm. An analytical reference standard for nicosulfuron with an expiration date of 09/03/2018 is available at EPA’s National Pes ticide Standards Repository (e

- mail dated 05/11/2015 from Theresa Cole, Analytical Chemistry Branch/Biological and Economic Analysis Division).
At this time, there are no Codex maximum residue limits (MRLs) established for residues of nicosulfuron. Cana dian MRLs are established on blueberries and corn and are expressed in terms of nicosulfuron. US tolerances and Canadian MRLs are harmonized for field corn grain. Canada does not establish tolerances on livestock feed items, whereas the US does. Canada h as not established tolerances for residues on livestock commodities. Refer to Appendix E

.

2.2 Use Profile & Anticipated Exposure Pathways

Nicosulfuron is formulated as dry flowable (DF) and liquid formulations. Currently registered labels include five technical/manufacturing use product labels and 27 end use product labels. In general, nicosulfuron may be applied once or tw ice per year or growing season. Registered use sites include corn (field, pop, seed, and sweet), herbicide

- resistant sorghum, non

- crop areas, and bermudagrass (including rights of way, non

- crop areas, airports, landing fields, grass/forage/fodder/hay, industrial areas, marshes bogs, no n

- agricultural rights of way, sewage disposal areas ) . Nicosulfuron may be applied using groundboom, aerial, and handheld

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

Page 4 of 32 application equipment; application via chemigation is prohibited on the registered labels. All the registered l abels require occupati onal handlers to wear long

- sleeved shirts, long pants, shoes, and socks. Some labels require the addition of chemical resistant gloves, waterproof gloves, aprons, coveralls, or dust mist respirators. The restricted entry intervals (REIs) range from 4 hou rs to 24 hours on the registered nicosulfuron labels ; labels with REIs greater than 4 hours and that require additional PPE beyond baseline attire and chemical resistant gloves are all products co

formulated with other pesticide active ingredients

. Indi viduals may be exposed to nicosulfuron via their diet (food and drinking water). There are no registered uses for nicosulfuron that will result in direct non

- dietary (i.e., residential) exposures. However, there is the potential for indirect non

- dietary exposure (incidental oral and dermal) to nicosulfuron related to spray drift . Agricultural workers may be exposed (dermal and inhalation) to nicosulfuron during mixing, loading, and/or applying the herbicide as well as during post

- application activities. Exposure to nicosulfuron is expected to be short

- and intermediate

- term for occupational handlers and post

- application workers. However, since the toxicity POD is the same for both durations, the handler and post

- application assessment is protective of b oth durations. Exposure to nicosulfuron via spray drift is expected to be short

- term only.

Table 2. 1 . Summary of Directions for Use of Nicosulfuron.

Applic. Timing, Type, and Equip. Formula

tion [EPA Reg. No.] Max.

Applic. Rate (lb ai/A) Max. No.

App lic.
per Season/ Y ear Max.

Seasonal Applic. Rate (lb ai/A) PHI (Days) Use Directions and Limitations

Corn (Field, Sweet, Seed, and Pop)

Post

emergence; Groundboom, Aerial 1 DF 0.062 2 0.062

30

- 85 Application may be applied when corn is up to 20 inches tall or that is exhibiting up to and including 6 leaf collars (V6). Best results are obtained when applications are made to young actively growing weeds. Use of a spray adjuvant is required or a combination adjuvant containing NIS, COC, MSO 4 and/or ammoni um nitrogen fertilizer. Liquid 0.063 2 0.063

Bermudagrass 2

Post

emergence; Ground boom

, Aerial, Handheld 1 DF 0.049 (broadcast) 0.053 lb ai/A or 0.025 oz/gal (spot) 2 0.088 0 5 Application is to be made to Bermuda grass that has been established for at least one growing season, when broadleaf weeds are <4” and grass weeds are <2” tall or in diameter. Use of a spray adjuvant is required or a combination adjuvant containing NIS, COC 4 , and/or ammonium sulfate or urea/ammonium nitrate fertilizer. Switchgrass Grown in Tennessee

Post

emergence; Ground boom, Aerial 1 DF 0.035 2 0.070 (implied)

0.088 (general restriction) 0 5 Application is to be made after the

switchgrass has reached the 2

- leaf stage, when weeds are young and actively growing. Use

of an NIS is required.

Herbicide

- Resistant Sorghum

Post

emergence; DF 0.062 2 0.084 Grain and Application is to be made to emerged

sorghum that is up to 20 inches tall. Applications made to 4

- 20 inch tall sorghum

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

Page 5 of 32 Table 2. 1 . Summary of Directions for Use of Nicosulfuron.

Applic. Timing, Type, and Equip. Formula

tion [EPA Reg. No.] Max.

Applic. Rate (lb ai/A) Max. No.

App lic.
per Season/ Y ear Max.

Seasonal Applic. Rate (lb ai/A) PHI (Days) Use Directions and Limitations

Groundboom, Aerial 1 stover

69
Forage

- 48 (V3

- V7 stage) are recommended for best weed control and crop tolerance. Apply to young actively growing weeds. Use of a spray adjuvant is required or a combination adjuvant containing NIS, COC, MSO 4 and/or ammonium nitrogen fertilizer.
Non

- Crop Areas 3

Groundboom, Aerial, Handheld 1 DF 0.07 lb ai/A 0.00082 lb ai/gal 2 0.14 N/A

1. Chemigation is not permitted on the registered labels. 2. Registered Bermudagrass use sites include: rights of way, non

- crop areas, airports, landing fields, grass/forage/fodder/hay, industrial areas, marshes bogs, non

- agricultural rights of way, and sewage disposal areas. 3. Non

- crop areas includ e : Fencerows, etc. May also be used selectively in established bermudagrass rough turf to control weeds) Industrial area/turf only. 4. NIS = Nonionic Surfactant. COC = Crop Oil Concentrate. MSO = Methylated Seed oil 5. The label states that there are no grazing or haying restrictions.



### 2.3 Consideration of Environmental Justice
Potential areas of environmental justice concerns, to the extent possible, were considered in the preliminary human health risk assessment for nicosulfuron , in accordance wi th U.S. Executive Order 12898, Federal Actions to Address Environmental Justice in Minority Populat ions and Low

- Income Populations 1 

### . As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well

- established procedures. In line with OPP policy, HED estimates risks to population subgroups from pesticide exposures that a re based on patterns of that subgroup’s food and water consumption, and activities in and around the home that involve pesticide use in a residential setting. Extensive data on food consumption patterns are compiled by the USDA under the National Health a nd Nutrition Examination Surveys/What We Eat in America (NHANES/WWEIA) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and categorized by subgroups based
on age and ethnic group. Additionall y, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, non

- dietary exposures based on home use of pesticide products and associated risks for adult applicators and for toddlers, youths, and adults entering or playing on treated areas post

- application are evaluated. Further considerations are currently in development as OPP has committed resources and expertise to the development of

s pecialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.

1 http://epa.gov/compliance/ej/resources/policy/exec_order_12898.pdf

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

Page 6 of 32 3 .0 Hazard Characterization
No new toxicity and/or metabolism data have been received sin ce the last risk assessment. This assessment is a summary of prior assessments (K. Rury, D408756, 06/26/2014).

3 .1 Summary of Toxicological Effects
Nicosulfuron inhibits the action of the plant enzyme acetolactate synthase (ALS)/acetohydroxy acid synthas e (AHAS), leading to the disruption of cell division and elongation in the plant. ALS is not found in humans or other mammals . A gene coding for a similar protein (ilvB

- like, ILVBL, also known as bacterial acetolactate synthase

- like) has been found in hu mans, however the protein or function associated with this gene is not known

. Therefore

, the herbicidal mode of action of nicosulfuron is not relevant to mammals

. Upon oral administration to rats , nicosulfuron appea rs to be incompletely absorbed, and is

m ostly excreted unchanged in feces (80

- 95%) and urine (9

- 20%) with trace residues in tissues. Minor metabolites of hydrolytic and oxidative metabolism were identified. A dermal absorption study is not available , therefore a default 100% dermal absorption factor is used in this risk

assessment

. In repeated dose studies by the oral route, nicosulfuron is minimally toxic, and rodents are particularly insensitive to its effe cts. Dietary administration at or near the limit dose (1000 mg/kg/day) to rats for 24 months or to mice for 18 months did not produce adverse effects. Dietary administration to dogs for one year produced mild effects (increase in the relative liver and kidney weights of males) at the highest doses tested (500 mg/kg/day).

Nicosulfuron show ed no developmental effects in rats, but produced abortions in rabbits at doses that also showed maternal toxicity. Decreased litter size was observed in a rat reproductive study from dams feed nicosulfuron levels above the limit dose . There are no indications of neurotoxic or immunotoxic effects elicited by nicosulfuron in animal studies. Nicosulfuron is not likely to be carcinogenic based on studies in the rat and mouse and lack of in vitro and in vivo mutagenic effects.

3 .2 Safe ty Factor for Infants and Children (FQPA Safety Factor)
The toxicity database of nico sulfuron is complete and adequate to assess the qualitative or quantitative susceptibility in the young. There is no evidence of increased qualitative or quantitative sus ceptibility in the young, there is no evidence of neurotoxicity

, and exposure estimates are unlikely to underestimate risk; therefore, the FQPA Safety Factor (10 X ) is reduced to 1 X

.

3 .3 Toxicity Endpoint and Point of Departure Selections

T here have been no changes to the prior dose

- response assessment or cancer classification (K. Rury, D408756, 06/26/2014) . The toxicity e ndpoints and points of departu res are presented in Table 3.1 , and a summary of the toxicological database used as the rationale for the selections is presented in Appendix A.

T here have been no changes to the prior recommendations for combining routes of exposure

. There are no registered residential uses proposed of nicosulfuron. F or occupational uses of nicosulfuron, because the dermal and inhalation POD are the same, dermal and inhalation risk

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

Page 7 of 32 estimates have been combined.

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

- Occupation al , and Occupational Human Health Risk Assessments

Exposure/ Scenario Point of Departure Uncertainty/

FQPA Safety Factors RfD, PAD, Level

of Concern for Risk Assessment Study and Toxicological

Effects

Acute Dietary (General Population, including Infants and Children and Females 13

- 49 years of
age ) N o hazard was identified from appropriate oral toxicity studies including developmental toxicity studies in rats and rabbits.

Chronic Dietary (All Populations)

NOAEL= 125 mg/kg/day UF A = 10 x

UF H =10 x
FQPA SF= 1 x

DAF = 100% c RfD = 1.25

mg/kg/day

cPAD = 1.25 mg/kg/day Chronic oral study in

dogs.
LOAEL = 500 mg/kg/day based on increased relative liver and kidney weights in males.
Supported by rabbit developmental t oxicity study (LOAEL = 500 mg/kg/day, NOAEL = 100 mg/kg/day). Incidental or al (Short

- and Intermediate

- Term) Residential LOC for MOE = 100

Dermal Exposure (All durations) Occupational LOC for MOE = 100 Inhalation Exposure (Short

and Intermediate

- Term )

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

UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, c PAD = chronic populati on adjusted dose, c RfD = chronic reference dose , MOE = margin of exposure, LOC = level of concern, NA = Not Applicable , FQPA = Food Quality Protection Act , DAF = dermal absorption factor

.



### 3 .4 Endocrine Disruption
As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic

, and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For eco logical hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic
groups. As part of its most recent registration decision for nicosulfuron

, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), nicosulfuron is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).
EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect

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

Page 8 of 32 produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to inter act with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA wil l determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and establish a dose

- response relationship between the dose and the E, A, or T effect.
Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingred ients and 9 inert ingredients. A second list of che micals identified for EDSP screening was published on June 14, 2013 2 

### and includes some pesticides s che duled for Registration Review and che micals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disruptors.
For further information on the status of the EDSP, the policies and procedures, the list s of che micals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website. 3



### 4.0 Residue Chemistry

The nature of the residue in corn and canola metabolism studies is adequate to satisfy data requirements for the registered crops. The nature of the residue in livestock is adequately understood based on metabolism studies on dairy cows and laying hens

. HED has determined that the residue of concern ( ROC ) for tolerance enforcement and risk assessment is the parent compound (nicosulfuron) for plants and livestock. The need for additional plant metabolism studies to support future uses wi ll be decided on a case

- by

- case basis (D302694, D. Hrdy, 11/30/2004)

. Adequate high performance liquid chromatography methods with tandem mass spectroscopic detection (HPLC/MS/MS) are available for tolerance enforcement of grass and sorghum commodities ( DuPont

- 17928 and DuPont

- 32277) (D360897, W. Drew, 11/6/2009 and D417854, M. Negussie, 03/17/2014). An HPLC/UV (ultraviolet) method is available for tolerance enforcement of corn commodities (D302694, D. Hrdy, 11/30/2004). T he methods have been adequately validated for the determination of residues of nicosulfuron in plant s

. The LC /MS/MS method determines residues of parent and metabolite 2

- aminosulfonyl]

- N,N

dimethyl

- 3

- pyridinecarboxamide (IN

- V9367) separately. The method limit of quantitation (LOQ) is 0.010 ppm for each analyte in all matrices.
Multiresidue methods testing data were previously submitted for nicosulfuron, which indicated

2 See http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of chemicals.

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

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

Page 9 of 32 that the methods are not applicable to nicosulfuron determination.
The structure and the physical/chemical propert ies are summarized in Appendix C

.

5.0 Dietary Risk Assessment

F or th is DRA

, a n updated dietary exposure assessment has been completed for nicosulfuron to incorporate updated food consumption data and drinking water modeling estimates. The use pattern, P ODs, and residue inputs to the dietary assessment have not changed since the previous

assessment.

5.1 Water Residue Profile
Screening ground water

- sourced drinking water exposure estimates were generated with the Pesticide Root Zone Model for Ground Wate r ( PRZM

- GW; v.1.07) for use in the SU dietary risk assessments. Rather than produce chemical

- specific estimated drinking water concentrations (EDWCs) following the usual assessment procedures, the Environmental Fate and Effects Division ( EFED ) provided coarse

- screen estimates that should exceed upper

- bound chemical

specific EDWCs for any SU. This was achieved by using model inputs that represent the use pattern of highest exposure from any SU, the highest soil mobility of any SU residue of con cern, and persistence to any route of degradation over time. The resulting highest coarse

- screen EDWCs from PRZM

- GW can be used as conservative screening

- level estimates of exposure and are summarized in Table 5. 1 ( G. Orrick, D427429, 8/12/2015 ).

The ch ronic dietary assessments for nicosulfuron used the post

- breakthrough mean value of 492 μg/L (0.492 ppm) from the North Carolina cotton scenario

.
Table 5.1 . PRZM

- GW Coarse

- Screen EDWCs for Sulfonylureas 1

.

Modeled Scenario K d or K OC Initial Application Dates (days post

emergence) Max. Daily Conc.

(μg/L) Mean

Breakthrough Time (yrs) Post

breakthrough Mean (μg/L)

WI corn K d 7 449 11.5 415

K OC 7 504 6.9 425

DMV corn K d 7 489 5.3 369

K OC 7 560 3.3 378

FL citrus K d 7 429 3.2 351

K OC 7 467 2.3 349

FL potato K d 7 375 2.6 272

K OC 7 407 2.2 275

GA peanut K d 7 197 5.2 156

K OC 7 206 3.9 158

NC cotton K d 7 640 8.7 492

K d 37 641 8.7 491

K d 67 637 8.7 490

K OC 7 742 5.7 484

K OC 37 751 5.7 483

K OC 67 744 5.7 482

1 Maximum values are bolded and were used in the chronic dietary assessment

.

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

Page 10 of 32 5. 2 Dietary (Food + Water) Exposure Assessment
HED has conducted a screening

- level chronic dietary risk assessment for nicosulfuron using tolerance

- level residues in foods and a sulfonylurea

- class

- wide sc reening

- level estimate of residues in drinking water (G. Orrick, D427429, 8/12/2015 ) . Exposure and risk estimates were obtained from the Dietary Exposure Evaluation Model using the Food Commodity Intake Database (DEEM

- FCID; version 3.16 ). The model uses food consumption data from the 200 3

- 2008 NHANES /WWEIA (National Health and Nutrition Examination Survey , What We Eat in America ) database, coupled with recipe files and residues in foods, to derive estimates of dietary exposure and risk. Generally, HED is concerned when chronic dietary exposure estimates exceed 100% of the chronic population adjusted dose ( c PAD). In the case of nicosulfuron , the dietary risk estimates (Table 5 .2 ) range from < 1 .0 to 2.2 % of the cPAD and are below HED’s level of concern. Because of the very conservative assumptions used in the analysis (tolerance

level residues, 100% crop treated, default processing f actors, upper

- bound modeled drinking water estimates), actual exposure and risk are expected to be much lower than those shown in Table 5 .2 . The listings of inputs and outputs to the assessment are included in Appendix B. HED did not conduct an acute dietary exposure/risk assessment because an acute dietary POD was not selected for nicosulfuron. Nicosulfuron is considered “not likely to be carcinogenic to humans”; therefore

, cancer risk is not a concern

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

Population Group Chronic Estimates

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

General US Population 0.010525 <1.0
All Infants (< 1 year old) 0.026963 2.2

Children 1

- 2 years old 0.015634 1.3

Children 3

- 5 years old 0.013125 1.0

Children 6

- 12 years old 0.009434 <1.0

Youth 13

- 19 years old 0.007753 <1.0

Adults 20

- 49 years old 0.010451 <1.0

Adults 50

- 99 years old 0.010280 <1.0

Female 13

- 49 years old 0.010407 <1.0



### 6.0 Residential (Non

- Occupational) Exposure/Risk Characterization
There are no registered residential uses or occupational uses resulting in residential exposure to nicosulfuron. Therefore, a quantitative residential exposure assessment was not performed.

6. 1 Spray Drift

Off

- target movement of pesticides can occur via many types of pathways and it is governed by a variety of factors. Sprays that are released and do not deposit in the application area end up off

target and can lead to exposures to those it may directly contact. They can also deposit on surfaces where c ontact with residues can eventually lead to indirect exposures ( e.g. , children

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

Page 11 of 32 playing on lawns where residues have deposited next to treated fields). The potential risk estimates from these residues can be calculated using drift modeling onto 50 feet wide lawns coupled with methods employed for residential risk assessments for turf products.
The approach to be used for quantitatively incorporating spray drift into risk assessment is based on a premise of compliant applications which, by definition, should not result in direct exposures to individuals because of existing label langua ge and other regulatory requirements intended to prevent them. 4


### Direct exposures would include inhalation of the spray plume or being sprayed directly. Rather, the exposures addressed here are thought to occur indirectly through contact with impacted a reas, such as residential lawns, when compliant applications are conducted. Given this premise, exposures for children (1 to 2 years old) and adults who have contact with turf where residues are assumed to have deposited via spray drift thus resulting in an indirect exposure are the focus of this analysis analogous to how exposures to turf products are considered in risk assessment.
In order to evaluate the drift potential and associated risks, an approach based on drift modeling coupled with techniques used to evaluate residential uses of pesticides was utilized. Essentially, a residential turf assessment based on exposure to deposited residues has been completed to address drift from the agricultural applications of nicosulfuron

. In the spray drift sce nario, the deposited residue value was determined based on the amount of spray drift that may occur at varying distances from the edge of the treated field using the AgDrift (v2.1.1) model and the Residential Exposure Assessment Standard Operating Procedur es Addenda 1: Consideration of Spray Drift Policy . Once the deposited residue values were determined, the remainder of the spray drift assessment was based on the algorithms and input values specified in the recently revised (2012) Standard Operating Proce dures For Residential Risk Assessment (SOPs)

. A screening approach was developed based on the use of the AgDrift model in situations where specific label guidance that defines application parameters is not available. 2 

### AgDrift is appropriate for use only w hen applications are made by aircraft, airblast orchard sprayers, and groundboom sprayers. When AgDrift was developed, a series of screening values (i.e., the Tier 1 option) were incorporated into the model and represent each equipment type and use under varied conditions. The screening options specifically recommended in this methodology were selected because they are plausible and represent a reasonable upper bound level of drift for common application methods in agriculture. These screening options ar e consistent with how spray drift is considered in a number of ecological risk assessments and in the process used to develop drinking water concentrations used for risk assessment. In all cases, each scenario is to be evaluated unless it is not plausible based on the anticipated use pattern (e.g., herbicides are not typically applied to tree canopies) or specific label prohibitions (e.g., aerial applications are not allowed). Section 6.1.1 provides the screening level drift related risk estimates.

In ma ny cases, risks are of concern when the screening level estimates for spray drift are used as the basis for the analysis. In order to account for this issue and to provide additional risk management options additional spray drift deposition fractions were also considered. These drift

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

2 http://www.epa.gov/pesticides/science/models_pg.htm

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

Page 12 of 32 estimates represent plausib le options for pesticide labels.

6.1.1 Combined Risk Estimates From Lawn Deposition Adjacent to Applications
The spray drift risk estimates are based on an estimated deposited residue concentratio n as a result of the screening level agricultural application scenarios. Nicosulfuron is used on corn, sorghum, bermudagrass, and non

- crop areas and can be applied via aerial, groundboom, and handheld equipment. The recommended drift scenario screening l evel options are listed below:

 Groundboom applications are based on the AgDrift option for high boom height and using very fine to fine spray type using the 90 th 

### percentile results.

 Aerial applications are based on the use of AgDrift Tier 1 aerial option for a fine to medium spray type and a series of other parameters which will be described in more detail below (e.g., wind vector assumed to be 10 mph in a downwind direction for entire application/drift event). 1



### Dermal and incidental oral risk estimates w ere combined because the toxicity endpoint for each route of exposure is based on increased relative liver and kidney weights from the same study

. The total applicable Level of Concern is 100; therefore MOEs < 100 are of concern. Adult dermal and c hildren’s (1 to <2 year old) dermal and incidental oral risk estimates from indirect exposure to nicosulfuron related to spray drift result in no risks of concern at field edge.

Table 6.1.1. Adult Dermal Risk Estimates (MOEs) Related to Spray Drift Expo sure to Nicosulfuron from the Registered Agricultural Uses. Application Type Spray Type/Nozzle

Configuration Appl. Rate (lb ai/A) TTR

(μg/cm 2 ) 2 At Edge

(LOC = 100) Corn 1
Aerial Fine to Medium 0.063 0.0070 21,000 Groundboom High Boom Very fine to Fine 28,000 Bermudagrass 1
Aerial Fine to Medium 0.049 0.00544 26,000 Groundboom High Boom Very fine to Fine 36,000 Non

- Crop Areas 1
Aerial Fine to Medium 0.07 0.0078 19,000 Groundboom High Boom Very fine to Fine 25,000 Sorghum 1
Aerial Fine to Medium 0.062 0.0069 21,000 Groundboom High Boom Very fine to Fine 29,000

1 Assessed using the highest registered application rates.

2 HED’s default assumption that 10% of the application is available for transfer on day 0 fo llowing the application and the residues dissipate at a rate of 10% each following day.

1 AgDrift allows for consideration of even finer spray patterns characterized as very fine to fine. However, thi s spray pattern was not selected as the common screening basis since it is used less commonly for most agriculture.

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

Page 13 of 32 Table 6.1.2. Combined Dermal and Hand

- to

- Mouth Exposure for Children 1 to <2 Years Old Risk Estimates (MOEs) Related to Spray Drift Exposure to Nicosulfuron from the Registered Agricultural Uses. Application Type Spray Type/Nozzle

Configuration Appl. Rate (lb ai/A) TTR

(μg/cm 2 ) 2 At Edge

(LOC = 100) Corn 1
Aerial Fine to Medium 0.063 0.0070 10,000 Groundboom High Boom Very fine to Fine 14,000 Bermudagrass 1
Aerial Fine to Medium 0.049 0.00544 13,000 Groundboom High Boom Very fine to Fine 18,000 Non

- Crop Areas 1
Aerial Fine to Medium 0.07 0.0078 9,200 Groundboom High Boom Very fine to Fine 13,000 Sorghum 1
Aerial Fine to Medium 0.062 0.0069 10,000 Groundboom High Boom Very fine to Fine 14,000

1 Assessed using the highest registered application rates.

2 HED’s default assumption that 10% of the application is available for transfer on day 0 following the application and the residues dissipate at a rate of 10% each following day.



### 6. 2 Residential Bystander Post

- Application Inhalation Exposure

Volatilization of pesticides may be a source of post

- application inhalation exposure to individuals nearby pesticide applications. The A gency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and R odenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The A gency has evaluated the SAP report and has developed a Volatiliza tion Screening Tool and a subsequent Volatilization Screening Analysis. 1 

### During Registration Review, the A gency will utilize this analysis to determine if data (i.e., flux studies, route

- specific inhalation toxicological studies) or further analysis is re quired for nicosulfuron

.

7.0 Aggregate Exposure/Risk Characterization
The Food Quality Protection Act of 1996 directs EPA to assess aggregate exposure to pesticide chemical residues, including all anticipated dietary exposures and all other exposures for w hich there is reliable information. In the case of nicosulfuron , aggregate exposure and risk estimates are equivalent to the dietary exposure and risk estimates in Section 5 .2 and are not of concern. There are no registered uses for nicosulfuron that wil l result in direct non

- dietary (i.e., residential) exposures. However, there is the potential for indirect non

- dietary exposure (incidental oral and dermal) to nicosulfuron related to spray drift. Residential exposures resulting from spray drift are not included in the aggregate assessment because the likelihood of

1 Available at: http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219

.

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

Page 14 of 32 co

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

8.0 Cumulative Exposure/Risk Characterization In 2015, EPA’s Office of Pesticide Programs released a guidance document entitled, Pesticide Cumulative Risk Assessment: Framework for Screening Analysis 1 

### . This document provides guidance on how to screen groups of pesticides for cumulative evaluation using a two

- step approach beginning with the evaluation of availabl e toxicological information and if necessary, followed by a risk

- based screening approach. This framework supplements the existing guidance documents for establishing common mechanism groups (CMGs) 2 

### and conducting cumulative risk assessments (CRA) 3 

### . The Agency has utilized this framework to evaluate the SUs of which [chemical name] is a member (J. D’Agostino; D428798; 9/9/15). Although the SUs share some chemical and toxicological characteristics, the toxicological database does not support a testable hy pothesis for a common mechanism of action. No further mechanistic data are required and no further cumulative evaluation is necessary.

9.0 Occupational Exposure/Risk Characterization

9.1 Occupational Handler Exposure
There is potential occupational handler dermal and inhalation exposure from the registered uses of nicosulfuron. The quantitative exposure/risk assessment developed for occupational handle r s is based on the scenarios listed in Table 9.1

. Dermal and inhalation exposures were combined in this assessment, since the toxicological effects for these exposure routes were similar. On ly short

- and intermediate

- term exposures are expected for nicosulfuron ; and the PODs selected to evaluate dermal and inhalation exposures covers both durations.
The standard body weight (80 kg) was used in this risk assessment since the endpoint selected was not developmental and/or based on fetal effects. Since no inhalation absorption data are available, toxicity by the inhalation route is considered to be eq uivalent to the estimated toxicity by the oral route of exposure.
All occupational handler scenarios for the registered uses resulted in MOEs greater than 100 at baseline level of risk mitigation (i.e., baseline attire with no gloves or respira tor) or engineering control for aerial applications (i.e., enclosed cockpits) and, therefore, are not of concern. The lowest combined (dermal + inhalation) MOE of 500 is associated with mixing/loading /applying a dry flowable formulation to industrial/comm ercial areas (non

- crop areas)

.

1 http://www.epa.gov/oppfead1/cb/csb_page/updates/2015/f ramew ork

- for

- screening

- analysis.html

2 Guidance For Identifying Pesticide Chemicals and Other Substances that have a Common Mechanism of Toxicity (USEPA, 1999)

3 Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a Common Mechanism of Toxicity (USEPA, 2002)

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

Page 15 of 32 Table 9.1 . Occupational Handler Short

- and Intermediate

- Term Non

- Cancer Exposure and Risk Estimates for Nicosulfuron.

Exposure Scenario Crop or Target Level of Concern Dermal

Unit Exposure (μg/lb ai) 1 Inhalation

Unit Exposure (μg/lb ai) 1 Maximum

Application Rate 2 Area

Treated or Amount Handled Daily 3 Dermal Inhalation Combined

Baseline Baseline Dose (mg/kg/day) 4 MOE 5 Dose

(mg/kg/day) 6 MOE 7 MOE 8

Mixer/Loader Mixing/Loading Dry Flowables for Aerial Application Non

- Crop Areas 9

100 227 8.96 0. 0 7 lb ai/A 350 A 0.0695 1,800 0.00275 45,000 1,700

Corn & Sorghum 0.62 lb ai/A 1200 A 0.211 590 0.00834 15,000 570
Mixing/Loading Dry Flowables for Groundboom Application Non

- Crop Areas 9 0.07 lb ai/A 80 A 0.0159 7,900 0.000628 200,000 7,600

Corn & Sorghum 0.062 lb ai/A 200 A 0.0351 3,600 0.00139 90,000 3,500

Mixing/Loading Liquids for Aerial Application Non

- Crop Areas 9

220 0.219 0.07 lb ai/A 350 A 0.0674 1,900 0.0000671 1,900,000 1,900

Corn 0.063 lb ai/A 1200 A 0.208 600 0.000208 600,000 600

Mixing/Loading Liquids for Groundboom Application Corn 0.063 lb ai/A 200 A 0.0346 3,600 0.0000345 3,600,000 3,600

Applicator Applying Sprays via Aerial Equipment Non

- Crop Areas 9

100 2.08 0.0049 0.07 lb ai/A 350 A 0.000638 200,000 0.0000015 83,000,000 200,000

Corn & Sorghum 0.063 lb ai/A 1200 A 0.00196 64,000 0.00000463 27,000,000 64,000

Applying Sprays via Groundboom Equipment Non

- Crop Areas 9
78.6 0.34 0.07 lb ai/A 80 A 0.0055 23,000 0.0000238 5,300,000 23,000

Corn & Sorghum 200 A 0.0124 10,000 0.0000535 2,300,000 10,000
Applying Sprays via Mechanically Pressurized Handgun Non

- Crop Areas 9 1300 3.9 0.005 lb ai/gal 1000 gal 0.0813 1,500 0.000244 510,000 1,500

Flagger Flagging for Aerial Application Non

- Crop Areas 9
100 11 0.35 0.07 lb ai/A
350 A 0.00338 37,000 0.000107 1,200,000 36,000

Corn & Sorghum 0.063 lb ai/A 0.00304 41,000 0.0000965 1,300,000 40,000

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

Page 16 of 32 Table 9.1 . Occupational Handler Short

- and Intermediate

- Term Non

- Cancer Exposure and Risk Estimates for Nicosulfuron.

Exposure Scenario Crop or Target Level of Concern Dermal

Unit Exposure (μg/lb ai) 1 Inhalation

Unit Exposure (μg/lb ai) 1 Maximum

Application Rate 2 Area

Treated or Amount Handled Daily 3 Dermal Inhalation Combined

Baseline Baseline Dose (mg/kg/day) 4 MOE 5 Dose

(mg/kg/day) 6 MOE 7 MOE 8

Mixer/loader/Applicator

Mixing/Loading/ Applying Sprays via Backpack Sprayers Non

- Crop Areas 9

( Rights

- of

- Way )

100 8260 2.58

0.005 lb ai/gal 40 gal 0.0206 6,100 0.00000645 19,000,000 6,100

Non

- Crop Areas 9 ( Industrial/ Commercial Areas ) 2510 30 0.00628 20,000 0.000075 1,700,000 20,000

Mixing/Loading/ Applying Sprays via Manually Pressurized Handwand Non

- Crop Areas 9

( Industrial/ Commercial Areas ) 100,000 30 0.25 500 0.000075 1,700,000 500

Mixing/Loading/ Applying Sprays via Mechanically Pressurized Handgun Non

- Crop Areas 9

( Industrial/ Commercial Areas ) 1,300 3.9 1000 gal 0.0813 1,500 0.000244 510,000 1,500

Non

- Crop Areas 9 1,300 3.9 0.0813 1,500 0.000244 510,000 1,500

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (02/01/2015); Level of mitigation: Base line. Note that aerial applicators are assessed as enclosed cockpit and baseline represents engineering controls.

2 Based on reg istered nicosulfuron labels.

3 Exposure Science Advisory Council Policy #9.1.

4 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) × DAF (10 0%) ÷ BW (80 kg).

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

6 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal ) × Area Treated or Amount Handled (A or gal/day) ÷ BW (80 kg).

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

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

9 Non

- crop areas include bermudagrass for the purposes of the occupational assessment. Registered Bermudagrass and non

- crop use sites include: fencerows, rights of way, non

crop areas, airports, landing fields, grass/forage/fodder/hay, industrial areas, mar shes bogs, non

- agricultural rights of way, and sewage disposal areas. Bermudagrass was also assessed using the “typical field crop”, “rights of way”, and “industrial/commercial” exposure inputs as surrogates to assess exposure. ai = active ingredient; A = acres ; gal = gallons

### Nicosulfuron Human Health Risk Ass essment DP No. D427029

Page 17 of 32 9.2 Occupational Post

- Application Exposure

Both short

- and intermediate

- term dermal and inhalation exposures are expected for occupational post

- application workers following nicosulfuron application.
Occupational Pos t

- Application Inhalation Exposure
Based on the Agency's current practices, a quantitative occupational post

- application inhalation exposure assessment was not performed for nicosulfuron at this time. If new policies or procedures are put into place, the A gency may revisit the need for a quantitative occupational post

- application inhalation exposure assessment for nicosulfuron

. Occupational Post

- application Dermal Exposure and Risk Estimates
The algorithms used to estimate non

- cancer exposure and dose for occupational post

- application workers can be found in the footnotes of Table 9.2

. Only low crop heights were assessed because nicosulfuron is applied early in the crop growing season for corn and sorghum. Post

application exposure is not expected to non

- crop areas and bermudagrass. It is unlikely workers would have to re

- enter treated areas following application to these areas. The highest registered application rate of the products registered on corn and sorghum was used as a conservative estimate of exposure (0.063 lb ai/A). The occupational post

- application MOEs ranged from 3,700 to 100,000 on day 0, and are not of concern.
Since the highest estimated occupational post

- application exposure using default dislodgeable foliar residue ( DFR ) values for nicosulfuron is minimal in comparison to the level of concern (i.e., the calculated MOE is greater than 2 times higher than the level of concern, MOE = 3,700 compared to the LOC of 100 ); EPA is waiving the 40 CFR DFR data requirement at this ti me for currently registered uses . In this instance, it is unlikely that chemical

- specific DFR data would be needed to further refine exposure assessments or would add appreciably to our overall understanding of the availability of dislodgeable foliar pest icide residues for nicosulfuron

. Table 9.2 . Occupational Post

- application Non

- Cancer Dermal Exposure and Risk Estimates for Nicosulfuron

.

Crop/Site Activities Transfer Coefficient (cm 2 /hr) DFR 1

( μg/cm 2 ) Dermal Dose

(mg/kg/day) 2 MOE 3

Short

- and Intermediate

- Term

Corn & Sorghum Scouting 210

0.18 0.0037 34,000

Hand

- Set Irrigation 1900 0.0336 3,700

Hand Weeding 70 0.00124 100,000

1 DFR = Application Rate × F × (1

- D) t × 4.54E8 μg/lb × 2.47E

- 8 acre/cm 2 ; wher e F = 0.25 and D = 0.10 per day.
2 Daily Dermal Dose = [DFR /TTR (μg/cm 2 ) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption ( 100 %)]  BW ( 80 kg). 3 MOE = POD ( 125 mg/kg/day) / Daily Dermal Dose.


### Restricted Entry Interval
Based on the acute toxicity categories and post

- application assessment for nicosulfuron, the Worker Protection Standard (WPS) Interim Restricted Entry Interval (REI) for nicosulfuron is 12

- hours. REIs may be further reduced if certain criteria are met in accordance with the

### Nicosulfuron Human Health Risk Ass essment DP No. D427029

Page 18 of 32 Pesticide Registration (PR) Notice 95

- 3 [Reduction of WPS Interim REIs for Certain Low Risk Pesticides] 11 

### . In PR Notice 95

- 3, there are a set of criteria listed for the active ingredient that must be met for chemicals to be eligible for a reduced REI. These criteria include:

1. The active ingredient is in Toxicity category III or IV based upon data for acute dermal toxicity, acute inhalation toxicity, primary skin irritation, and primary eye irritation. Acute oral toxicity data were used i f no acute dermal data were available. If EPA lacked data on primary skin irritation, acute inhalation, or primary eye irritation of the active ingredient, the Agency reviewed data on that end

- point for similar active ingredients (analogs), and excluded su ch active ingredients from consideration for the reduced REI, if the analog is in Toxicity Category I or II for that endpoint.

2. The active ingredient is not a dermal sensitizer (or in the case of biochemical and microbial active ingredients, no known report s of hypersensitivity exist).

3. The active ingredient is not a cholinesterase inhibitor (NMethyl carbamate and Organophosphate) as these chemicals are known to cause large numbers of pesticide poisonings and have the potential for serious neurological effect s.

4. No known reproductive, developmental, carcinogenic, or neurotoxic effects have been associated with the active ingredient. If active ingredients did not have data available for these chronic health effects, EPA considered data on appropriate chemical an d biological analogs. Active ingredients that have been classified as carcinogenic in Category B (probable human carcinogen) or Category C with a potency factor, Q* (possible human carcinogen, for which quantification of potential risk is considered approp riate), or are scheduled for the Health Effects Division's Cancer Peer Review process, were omitted from consideration.

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

- applicatio n exposures to the active ingredient.
Upon review of the criteria for the active ingredient only , it appears that nicosulfuron is consistent with the criteria in PRN 95

- 3 that allow for a 4

- hour REI. Note : The PR Notice also includes similar criteria for the end

- use product. These criteria have not been evaluated by
HED. Based solely on the active ingredient criteria, HED would recommend for reduction of the REI for nicosulfuron.

10.0 Public Health and Pesticide Epidemiology Data

E valuation of the OPP In cident Data System (IDS) (S. Recore, D398572, 2/14/12; includes incidents from January 1, 2006 through December 14, 2011) indicated that no single chemical nicosulfuron incidents were identified in the Uni ted States. In the aggregate IDS ( which reports in cidents of multiple chemical exposures at the same time) there were 5 incidents reported for nicosulfuron . Because it falls within the categories reported as counts (which includes minor, unknown or no effects), there is no unique report that provides det ails about the incident and single chemical incidents are not distinguished from multiple chemical incidents

. A high

11 Available: http://www.epa.gov/PR_Notices/pr95

- 3.html

### Nicosulfuron Human Health Risk Ass essment DP No. D427029

Page 19 of 32 frequency of incidents indicates there is a high potential for exposure and vice versa. However f or nicosulfuron , there appears to be a l ow potential for exposure. Nicosulfuron is not included in the Agricultural Health Study (AHS), and therefore, the AHS does not provide information for this report. There does not appear to be a concern at this time that would warrant further investigati on. The Agency will continue to monitor the incident information . I f a concern is triggered, additional analysis will be included in the risk assessment.

1 1 .0 References
Federal Register Notices
Receipt of Several Pesticide P etitions Filed for Residues of Pesticide Chemica ls in or on Various Commodities; Notice of filing of petitions and request for comment. 78 Federal Register 139 (19 July 2013), pp. 43115

- 43118.
Memoranda Relevant to Registration Review of Nicosulfuron

– Ris k Assessments

Author Barcode Date Title D. Hrdy D302694 11/30/2004 Nicosulfuron HED Chapter of the Reregistration Eligibility Decision Document (RED). A. Parmar D335236 10/18/2007 Nicosulfuron

- Side

- by

- Side Field Trials on Corn using Suspension Concentrate and Water Dispersible Granule Formulations. W. Cutchin D361732 7/14/2009 Nicosulfuron: Human Health Risk Assessment for Proposed Section 18 Use on Bermudagrass. M. Doherty D360807 10/27/2009 Nicosulfuron. Human Health Risk Assessment for the Proposed Use on Grasses.



### Memoranda Relevant to Registration Review of Nicosulfuron

– Incident Reports

Author Barcode Date Title S. Recore D398572 2/14/2012 Nicosulfuron: Review of Human Incidents



### Memoranda Relevant to Registration Review of Nicosulfuron

– Residue Chemistry

Author Barcode Date Title J. Stokes D207115,

D207117 N/A Nicosulfuron in/on Sweet Corn. Evaluation of Analytical Method and Residue Data. J. Stokes D221715,

D221718 6/9/1995 Nicosulfuron in/on Sweet Corn Amendments.

A. Parmar D338945,

D342602 10/18/2007 Nicosulfuron: Section 3 Registration of Nicosulfuron 2L (EPA File Symbol: 67760

- TU) for Use on Corn. Summary of Analytical Chemistry and Side

- by

- Side Residue Data. A. Parmar D346994 5/13/2008 Nicosulfuron. Request for Waiver of Sorghum Metabolism Study, Poultry Metabolism Study and Poultry Feeding Study.
W. Drew D360897 11/6/2009 Nicosulfuron: Petition Requesting Establishment of Permanent Tolerances (Associated with Section 3 Registration) for Residues Resulting fro m New Food/Feed Use of the Herbicide on Grasses. Summary of Analytical Chemistry and Residue Data. M. Doherty D374717 3/2/2010 Nicosulfuron

– Resolution of Analytical Method Deficiencies

### Nicosulfuron Human Health Risk Ass essment DP No. D427029

Page 20 of 32 Noted in HED Review D360897. M. Negussie D417854 03/17/2014 Nicosulfuron: Petition for the Establishment of Permanent Tolerances for Uses on Acetolactase Synthase (ALS) Tolerant Grain Sorghum. Summary of Analytical Chemistry and Residue Data. M. Negussie D417840 03/17/2014 Nicosulfuron: Chronic Aggregate Dietar y (Food plus Drinking Water) Exposure and Risk Assessments in Support of a Section 3 Registration on Acetolactase Synthase (ALS) Tolerant Grain Sorghum. G. Orrick, D427429, 8/12/2015 Drinking Water Exposure Assessment for the Registration R eview of 22 Sulfonylurea Herbicides



### Memoranda Relevant to Registration Review of Nicosulfuron

– Other

Author Barcode Date Title
J. Van Alstine TXR

0050011 8/2/12 Nicosulfuron: Summary of Hazard and Science Policy Council (HASPOC) Meetings of March 29, 2012: Recommendations on the requirement of 90

- day inhalation and 28

- day dermal toxicity studies and neurotoxicity screening battery.

### Nicosulfuron Human Health Risk Ass essment DP No. D427029

Page 21 of 32 A ppendix A . Toxicology Profile

A.1 Toxicology Data Requirements
The requirements (40 CFR § 158.340) for food uses of nicosulfuron are in the table below. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Study Technical
Required Satisfied
870.1100 Acute Oral Toxicity

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

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

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

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

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

................................ .......................... yes

yes

yes

yes

yes

yes yes

yes

yes

yes

yes

yes

870.3100 90

- Day Oral Toxicity in Rodents

................................ .. 870.3150 90

- Day Oral Toxicity in Nonrodents

............................. 870.3200 21/28

- Day Dermal Toxicity

................................ .......... 870.3250 90

- Day Dermal Toxicity

................................ ............... 870.3465 90

- Day Inhalation Toxicity

................................ ........... yes

yes

yes

no

yes yes

yes waived 1

– waived 1

870.3700a Prenatal Developmental Toxicity (rodent)

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

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

................................ yes

yes

yes yes

yes

yes 870.4100a Chronic Toxicity (rodent)

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

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

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

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

............... yes

yes

yes

yes

no 2

yes

2

yes

yes 870.5100 Mutagenicity

— Bacterial Reverse Mutation Test

.......... 870.5300 Mutagenicity

— Mammalian Cell Gene Mutation Test

.. 870.5385 Mutagenicity

— Structural Chromosomal Aberrations

... 870.5550 Mutagenicity

— Other Genotoxic Effects

....................... yes

yes

yes

yes yes

yes

yes

yes 870.6200a Acute Neurotoxicity Screening Battery (rat)

................. 870.6200b 90

- Day Neurotoxicity Screening Battery (rat)

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

................................ ....... yes

yes

no yes

yes

–
870.7485 Metabolism and Pharmacokinetics

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

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

................................ ............................. yes

no

yes yes

–
yes

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

2 A chronic/oncogenicity study is available for the rat, thus separate chronic and oncogenicity are not necessary.

### Nicosulfuron Human Health Risk Ass essment DP No. D427029

Page 22 of 32 A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Profile of Nicosulfuron

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

870.1100 Acute oral

– rat 40924205 LD 50 > 5000 mg/kg IV

870.1200 Acute dermal

– rabbit 40924207 LD 50 ≥ 2000 mg/kg III

870.1300 Acute inhalation

– rat 40924209 LC 50 ≥ 5.9 mg/L IV

870.2400 Acute eye irritation

– rabbit 41082602 Moderate eye irritant III

870.2500 Acute dermal irritation

– rabbit 41082603 Not an irritant IV

870.2600 Skin sensitization

– guinea pig 41082604 Not a sensitizer NA



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

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

870.3100

90

- Day Oral Toxicity in Rodents (rat) 41082607 (1988) Acceptable/guideline
0, 300, 1500, 7500 or 20,000 ppm
M: 0, 22, 107, 555

, 1495; F: 0, 26, 133, 685

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

LOAEL = could not be established

.

870.3150

90

- Day Oral Toxicity in nonrodent (dog) 41082606 (1988) Acceptable/guideline 0, 250, 5000, or 20,000 ppm
M: 0, 9, 172, 710; F: 0, 9, 171, 683 mg/kg/day NOAEL = 171 mg/kg/day ( F)

LOAEL = 683 mg/kg/day based on decreased neutrophils (F only)

.

870.3700a Prenatal developmental in rodent (rat) 41082608 (1988) Acceptable/guideline
0, 200, 1000 , 2500 or 6000 mg/kg/day Maternal NOAEL = 6000 mg/kg/day

LOAEL = could not be established

. Developmental NOAEL = 6000 mg/kg/day

LOAEL = could not be established.

870.3700b Prenatal developmental in nonrodent (rabbit) 41082609 (1988) Acceptable/guideline
0, 100, 5 00 , 1000 or 2000 mg/kg/day Materna l NOAEL = 100 mg/kg/day LOAEL = 500 mg/kg/day based on increased incidence vaginal discharge, abortion, staining of hair in rectal and vaginal areas, as well as increase d post

- implantation loss and decrease d body weight gain. Increased incidence of diarrhea at the next highest dose (1000 mg/kg/day). Developmenta l NOAEL = 1000 mg/kg/day

LOAEL could not be determined

.

### Nicosulfuron Human Health Risk Ass essment DP No. D427029

Page 23 of 32 Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Nicosulfuron

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

870.3800 Reproduction and Fertility Effects (rat) 41360101 (1989) Acceptable/guideline 0, 250, 5000 or 20

, 000
ppm M: 0, 15.6, 314, 1316 ; F: 19.5, 380, 1588 mg/kg/day Parental/Systemic NOAEL = 1203/1571 mg/kg/day (M/F)

LOAEL could not be established.

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

LOAEL = 1203/1571 mg/kg/day (M/F) based on decrease litter size from F 1 dams. Offspring NOAEL = 1203/1571 mg/kg/day (M/F)

LOAEL could not be established

.
870.4100b Chronic toxicity (dog) 41360102 (1989) Acceptable/guideline 0, 250, 5000 or 20,000 ppm 0, 6.25, 125, 500 mg/kg/day NOAEL = 125 mg/kg/day LOAEL = 500 mg/kg/day based on increase d relative liver and kidney weights in males

.

870.4200b Carcinogenicity (mouse) 41360103 (1989) Acceptable/guideline 0, 25, 250, 2500 or 7500 ppm
M: 3, 31 , 314, 953 ; F: 4, 43 , 420, 1260 mg/kg/day NOAEL = 953/1260 mg/kg/day (M/F)

LOAEL could not be established

. No evidence of carcinogenicity.

870.4300

Combined Chronic Toxicity/Carcinogenicity (rat) 41360104 (1989) Acceptable/guideline
0, 50, 1500, 7500 or 20

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

, 77, 382, 1098 mg/kg/day NOAEL = 786/ 1098 mg/kg/day (M/F)

LOAEL could not be established.

No evidence of carcinogenicity.

870.5100

Bacterial Reverse Mutation Test ( Salmonella typhimurium ) 41082612, 41360124 (1988) Acceptable/guideline

0.02

- 10 μg/plate (not all strains tested at the same concentrations) Negative in strains TA97A, TA98, TA100 and TA1535 at d oses reaching cytotoxic levels in the presence or absence of metabolic activation.

870.5300

In vitro Mammalian Cell Gene Mutation Test (Chinese Hamster Ovary (CHO) cells) 41082614, 41360123 (1988) Acceptable/guideline
4, 20, 40, 200 or 465 μg/mL Negative at doses reaching the limit of solubility in the presence or absence of metabolic activation.

870.5375

In vitro Mammalian Chromosome Aberration Test (human lymphocytes) 41082615, 41368001 (1988) Acceptable/guideline 0, 200, 400 or 470 μg/mL Negative at doses reaching the limit of solubility in the presence or absence of metabolic activation.

### Nicosulfuron Human Health Risk Ass essment DP No. D427029

Page 24 of 32 Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Nicosulfuron

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

870.5385

Mammalian Bone Marrow Chromosome Aberration Assay (mouse) 41082616, 41360126 (1988) Acceptable/guideline 0, 500, 2500 or 5000 mg/kg Negative for induction of chromosome aberrations in the bone marrow cells of male or female mice at 24, 48 or 72 hrs post

- exposure.

870.5550

Unscheduled DNA Synthesis in Mammalian Cells in Culture (rat hepatocytes) 41082613 , 41360125 (1998) Acceptable/ guideline
0.04, 0.4, 1.2, 4.1, 12, 41, 122, 409 or 470 μg/mL Negative for DN A damage or inducible repair in the rat hepatocyte

.

870.6200a Acute Neurotoxicity Screening Battery (rat) 48790905 (2011) Acceptable/guideline 0, 200, 1000, or 2000 mg/kg NOAEL = 2000 mg/kg/day

LOAEL = could not be established

.

870.6200b Subchronic Neurotoxicity Screening Battery (rat) 48790903 (2011) Acceptable/guideline 0, 2500, 7500 or 18000 ppm
M: 0, 145, 449 or 1101; F: 0, 181, 532 or 1295 mg/kg/day NOAEL = 1101/1295 mg/kg/day (M/F)

LOAEL = could not be established

.

870.7485

Metabolism and Pharmacokinetics (rat) 41082617 (1988) Acceptable/guideline Single dose oral: 10 or 1000 mg/kg Single dose iv: 10 mg/kg Repeated dose oral : 10 mg/kg/day for 14 days Most of a single oral dose was excreted unchanged within 24 hours and 98

- 109% within 4 days; the oral half

- life was 12

- 24 hours. 80

- 95% dose was eliminated in feces, 9

- 20% in urine and <0.01% in exhaled air. A slightly greater percent of the oral dose was detected i n feces of high dose than low dose animals. After iv administration, 76

- 80% dose was eliminated in urine and 27

- 30% in the feces; the iv half

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

- 0.5% dose; highest levels detected in the liver and kidneys. Th e major excretion product was unchanged parent compound. Pyridinesulfonamide was detected in urine (1.1

- 5.7% dose). Pyridine acid sulfonamide was tentatively identified as a minor metabolite in the feces of orally dosed rats and urine of iv dosed rats. The se metabolites represent hydrolytic cleavage/oxidation of the parent molecule. No differences were observed between sexes.

870.7800 Immunotoxicity (female mice) 48790904 (2011) Acceptable/guideline
0, 300, 900, 1800 or 7000 ppm
0, 60, 181, 333 or 1207 mg/kg/day NOAEL = 1207 mg/kg/day

LOAEL = could not be established

.

M = males, F = females, PND = post natal day

### Nicosulfuron Human Health Risk Ass essment DP No. D427029

Page 25 of 32 Appendix B. Dietary Exposure/Risk Modeling Input and Output

U.S. EPA Ver. 3.16, 03

- 08

- d

DEEM

- FCID Chronic analysis for NICOSULFURON

Residue file: C: \ Documents and Settings \ MNEGUSSI \ My Documents \ DEEM Version 3.16 \ Nicosulfuron \ Chronic_Nicosulfuron2015PRA.R08

Adjust. #2 NOT used

Analysis Date 05

- 12

- 2015 Residue file dated: 05

- 12

- 2015/09:33:56

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

Comment:Scoping

- PRA EDWC

- SU Coarse Screen Estimate

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

Fo od Crop Residue Adj.Factors

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

---------- ---- ------------------------------- ---------- ------ ------
3100044000 31 Beef, meat 0.010000 1.000 1.000

3100044001 31 Beef, meat

- babyfood 0.010000 1.000 1.000

3100045000 31 Beef, meat, dried 0.010000 1.920 1.000

3100046000 31 Beef, meat byproduct s 0.050000 1.000 1.000

3100046001 31 Beef, meat byproducts

- babyfood 0.050000 1.000 1.000

3100047000 31 Beef, fat 0.010000 1.000 1.000

3100047001 31 Beef, fat

- babyfood 0.010000 1.000 1.000

3100048000 31 Beef, kidney 0.050000 1.000 1.000

3100049000 31 Beef, liver 0.050000 1.000 1.000

3100049001 31 Beef, liver

- babyfood 0.050 000 1.000 1.000

1500120000 15 Corn, field, flour 0.100000 1.000 1.000

1500120001 15 Corn, field, flour

- babyfood 0.100000 1.000 1.000

1500121000 15 Corn, field, meal 0.100000 1.00 0 1.000

1500121001 15 Corn, field, meal

- babyfood 0.100000 1.000 1.000

1500122000 15 Corn, field, bran 0.100000 1.000 1.000

1500123000 15 Corn, field, starch 0.100000 1.000 1.000

1500123001 15 Corn, field, starch

- babyfood 0.100000 1.000 1.000

1500124000 15 Corn, field, syrup 0.100000 1.000 1.000

1500124001 15 Corn, field, syrup

- babyfood 0.100000 1.000 1.000

1500125000 15 Corn, field, oil 0.100000 1.000 1.000

1500125001 15 Corn, field, oil

- babyfood 0.100000 1.000 1.000

1500126000 15 Corn , pop 0.100000 1.000 1.000

1500127000 15 Corn, sweet 0.100000 1.000 1.000

1500127001 15 Corn, sweet

- babyfood 0.100000 1.000 1.000

3200169000 32 Goat, meat 0.010000 1.000 1.000

3200170000 32 Goat, meat byproducts 0.050000 1.000 1.000

### Nicosulfuron Human Health Risk Ass essment DP No. D427029

Page 26 of 32 3200171000 32 Goat, fat 0.010000 1.000 1.000

3200172000 32 Goat, kidney 0.050000 1.000 1.000

3200173000 32 Goat, liver 0.050000 1.000 1.000

3300189000 33 Horse, meat 0.010000 1.000 1.000

3800221000 38 Meat, game 0.010000 1.000 1.000

3600222000 36 Milk, fat 0.010000 1.000 1.000

3600222001 36 Milk, fat

- baby food/infant formu 0.010000 1.000 1.000

3600223000 36 Milk, nonfat solids 0.010000 1.000 1.000

3600223001 36 Milk, nonfat solids

- baby food/in 0.010000 1.000 1.000

3600224000 36 Milk, water 0.010000 1.000 1.000

3600224001 36 Milk, water

- babyfood/infant form 0.010000 1.000 1.000

3600225001 36 Milk, sugar (lactose)

- baby food/ 0.010000 1.000 1.000

3500339000 35 Sheep, meat 0.010000 1.000 1.000

3500339001 35 Sheep, meat

- babyfood 0.010000 1.000 1.000

3500340000 35 Sheep, meat byproducts 0.050000 1.000 1.000

3500341000 35 Sheep, fat 0.010000 1.000 1.000

3500341001 35 Sheep, fat

- babyfood 0.010000 1.000 1.000

3500342000 35 Sheep, kidney 0.050000 1.000 1.000

3500343000 35 Sheep, liver 0.050000 1.000 1.000

1500344000 15 Sorghum, grain 0.800000 1.000 1.000

1500345000 15 Sorghum, syrup 0.800000 1.000 1.000

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

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

U.S. EPA Ver. 3.16, 03

- 08

- d

DEEM

- FCID Chronic analysis for NICOSULFURON NHANES 2003

- 2008 2

- day

Residue file name: C: \ Documents and Settings \ MNEGUSSI \ My Documents \ DEEM Version 3.16 \ Nicosulfuron \ Chronic_Nic osulfuron2015PRA.R08

Adjustment factor #2 NOT used.

Analysis Date 05

- 12

- 2015/09:34:25 Residue file dated: 05

- 12

- 2015/09:33:56

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

COMMENT 1: Scoping

- PRA EDW C

- SU Coarse Screen Estimate

===============================================================================
Total exposure by population subgroup

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

Total Exposure

----------------------------------- Population mg/kg Percent of

### Nicosulfuron Human Health Risk Ass essment DP No. D427029

Page 27 of 32 Subgroup bo dy wt/day Rfd

-------------------------------------- ------------- ----------------
Total US Population 0.010525 0.8%

Hispanic 0.010116 0. 8%

Non

- Hisp

- White 0.010809 0.9%

Non

- Hisp

- Black 0.008724 0.7%

Non

- Hisp

- Other 0.012082 1.0%

Nursing Infants 0.009471 0.8%

Non

- Nursing Infants 0.034776 2.8%

Female 13+ PREG 0.009892 0.8%

Children 1

- 6 0.013843 1.1%

Children 7

- 12 0.008975 0.7%

Male 13

- 19 0.007353 0.6%

Female 13

- 19/NP 0.008144 0.7%

Male 20+ 0.009762 0.8%

Female 20+/NP 0.010956 0.9%

Seniors 55+ 0.010076 0.8%

All Infants 0.026963 2.2%

Female 13

- 50 0.010418 0.8%

Children 1

- 2 0.015634 1.3%

Children 3

- 5 0.013125 1.0%

Children 6

- 12 0.009434 0.8%

Youth 13

- 19 0.007753 0.6%

Adults 20

- 49 0.010451 0.8%

Adults 50

- 99 0.010280 0.8%

Female 13

- 49 0.010407 0.8%

### Nicosulfuron Human Health Risk Ass essment DP No. D427029

Page 28 of 32 Appendix C . Physical/Chemical Properties of Nicosulfuron and Metabolites

TABLE C .1. Physicochemical Properties of Nicosulfuron.

Parameter Value Reference

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

Ph 4.5 MRID #47632204
Density 1.441 ± 0.006 g/cm 3 relative density MRID #47632204
Water solubility (at 25°C) Anhydrous form (g/L)
pH 5 = 0.36
pH 7 = 12.2
pH 9 = 39.1 Monohydrate form (g/L)
pH 5 = 0.42
pH 7 = 7.4
pH 9 = 47.96 MRID #47632204

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

Acetone 18

Acetonitrile 23

Benzene 1.7

Chloroform 64

Dichloromethane 160
Dimethylformamide 64

Ethanol 4.5
Ethyl acetate 3.8

Hexane <0.02

Methanol 0.44

2

- Propanol 1.2
Tetrahydrofuran 26

Toluene 0.37
Xylenes 0.2 MRID #47632204

Vapor pressure (at 25°C) 1.2 x 10

- 16 Torr MRID #47632204
Dissociation constant, 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 (at 20°C) No absorbance maxima at or above 290 nm for acidic, basic or neutral solutions. MRID #47632204

### Nicosulfuron Human Health Risk Ass essment DP No. D427029

Page 29 of 32 TABLE C .2. Chemical Names and Structures of Nicosulfuron and Metabolites.

Company Code; Common Name Chemical Name Chemical Structure

IN

- V9367; pyridine sulfonamide [2

- aminosulfonyl]

- N

, N

- dimethyl

- 3

- pyridinecarboxamide

IN

- HYY21 or AUSN 2

- [[[[(Aminoiminomethyl) amino]carbonyl]amino]sulfonyl]

- N,N

- dimethyl

- 3

- pyridinecarboxamide

IN

- 37740 2

- [[(3,4

- dihydro

- 6

- methoxy

- 4

- oxopyrimidin

- 2

- yl]aminocarbonyl]aminosulfonyl]

- N

, N

- dimethyl

- 3

- pyridinecarboxamide

### Nicosulfuron Human Health Risk Ass essment DP No. D427029

Page 30 of 32 Appendix D

. Review of Human Research
This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. These data are subject to ethics review pursuant to 40 CFR § 26, have received that review, and are complian t with applicable ethics requirements. For certain studies that review may have included review by the Human Studies Review Board. Descriptions of data sources as well as guidance on their use can be found at: http://www.epa.gov/pesticides/science/handler

- exposure

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

- app

- exposure

- data.html

.

### Nicosulfuron Human Health Risk Ass essment DP No. D427029

Page 31 of 32 Appendix E

. International Harmonization

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

Residue Definition:

US Canada Mexico 1 Codex

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]carbonyl] amino]sulfonyl]

- N,N

dimethyl

- 3

- pyridinecarboxamide None

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

US Canada Mexico 1 Codex
Cattle, fat 0.01
Cattle, meat 0.01 Cattle, meat byproducts 0.05 Corn, field, forage 0.1 Corn, field, grain 0.1 0.1 corn
Corn, field, stover 0.1 Corn, pop, grain 0.1 Corn, pop, stover 0.1
Corn, sweet, forage 0.1 Corn, sweet, kernel plus cob with husks removed 0.1

Corn, sweet, stover 0.1
Goat, fat 0.01
Goat, meat 0.01 Goat, meat byproducts 0.05 Grass, forage 9.0 Grass, hay 25.0
Horse, fat 0.01
Horse, meat 0.01 Horse, meat byproducts 0.05

Milk 0.01 Sheep, fat 0.01 Sheep, meat 0.01 Sheep, meat byproducts 0.05 MRLs with No US Equivalents

Blueberries 0.05

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

### Nicosulfuron Human Health Risk Ass essment DP No. D427029

Page 32 of 32 Appendix F

. DFR Data Waiver Rationale
Dislodgeable Foliar Residue (DFR): In accordance with 40 CFR § 158, DFR data are required for all occupational (e.g., crop, nursery, greenhouse use sites) or residential (e.g., ornamental and vegetable gardens, pick your own farms, retail tree farms) uses that could result in post

application exposure to foliage. In the absence of chemical

- sp ecific DFR data, EPA uses default values. The 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment includes an analysis of a number of DFR studies, which resulted in the selection of a revised default values for the fraction of the application rate available for transfer after a foliar application (F AR 

### ). These values are based on an analysis of 19 DFR studies. Since that time, the Agricultural Re

- entry Task Force has submitted information (MRID 49299201) that corrects an appl ication rate error made in the original submission of “ARF039

– Determination of Dermal and Inhalation Exposure to Reentry Workers During Chrysanthemum Pinching in a Greenhouse” (EPA MRID 45344501). As a result, the range of F AR 

### values was revised from 2%

- 89% to 2%

- 47%. In the data, a large range of transferability is observed and this variability can potentially be attributable to many factors such as active ingredient; formulation; field conditions in the studies; weather conditions (e.g., humidity) ; or many other difficult to quantify factors. Although witnessed across multiple chemicals, this range in F AR 

### values is not expected when considering DFR data for a single chemical. At this time, the ARTF submission did not alter the selection of 25% as the reasonable, high

- end default value. Because DFR data are not available for nicosulfuron , EPA is using the default value of 25%. Although there may be a small degree of uncertainty in the use of the default DFR value for nicosulfuron (i.e., there is a small chance that the F AR 

### value may exceed the applicable default value ), it is likely that the health

- protective aspects of EPA’s occupational post

- application assessment methodology will more than compensate for this potential uncertainty. For example , when assessing residential and occupational post

- application exposure to gardens and ornamentals, EPA assumes the following:
exposures occur to zer o

- day (i.e., day of application ) residues every day of the assessed exposure duration (i.e., EPA assumes that no dissipation or degradation occurs, it doesn’t rain, etc); individuals perform the same post

- application activities performed in the transfer coefficient study day after day (e.g., weeding, harvesting, pruning, etc.); and individuals engage in thes e post

- application activities for a high

- end amount of time every day (represented by data reflecting time spent gardening based on survey data).
Given the conservatisms discussed above and the potential compounding nature of these conservatisms, EPA is ab le to rely upon the calculated exposure estimates with confidence that exposure is not being underestimated.
Since the highest estimated occupational post

- application exposure using default DFR values for nicosulfuron is minimal in comparison to the level of concern (i.e., the calculated MOE is greater than 2 times higher than the level of concern, MOE = 3,700 compared to the LOC of 100 ); EPA is waiving the 40 CFR DFR data requirement. In this instance, it is unlikely that chemical

specific DFR data would be needed to further refine exposure assessments or would add appreciably to our overall understanding of the availability of dislodgeable foliar pesticide residues for nicosulfuron

.