### UNITED STATES ENV IRO NMENTAL PROTECTIO N AGENCY

W ASHfNGTON, D.C. 20 4 60

MEMORANDUM

Date: Septe mber 10

, 2015 OF F ICE OF

CHEMICALSAFETYAN D

POLLUTION PREVE N TION

SUBJECT: Prosulfuron. Draft Human H ea l th Ri sk As sess m e nt in S upport of R eg istration

Review.

PC Code: 1290 3 1

Deci s ion No.: 502173
Petition No.: NA

Risk A ssess m e nt Type: Sing l e Chemical Aggregate

TXRNo.: NA
MRJD 

### No .: NA DP Barcodc: D426092 Registration No.: NA Regul atory Act ion : Registration Review

Case No.: 7235

CAS No .: 94 1 25-34-5

40 CFR: 

### § 180.481

FROM: Evisabel Craig, PhD, DABT

, Risk Assessor / Toxico lo gis t

# ~- 

# -!f}t.AJf,

.J 

### Monica Hawkins, P hD

, MPH, Environmental Hea lt h Scien tist

## 1{~ 

# Yf-VJll

Jul ie Yan A l stine, MPH

, Environmental H ea lth Sc i ent i s Wu.. 

# V:**~** 1 -...L • 

### Risk Assess ment Branch V I ·

### ~ ,7rl./ \,,

### rv**~** H ealth Effec ts Division (7509 P )

THROUGH: Donna Davi s, Br a n ch C hi ef

Risk Assess m e n t B ranc h V I

H ea lth Effects Di v i s i o n (7509P)

TO: Wi l helmena Livingston, Risk Manager Reviewe r Kevin Costello, Branch Chief

Risk Mana ge ment and Implementati on Br anch 

### IV

Pesticide R e-evalu ation D ivision (7508 P )

Page 1 

### of 32

### Table of Co ntent s

1.0 Exec uti ve su m

_ mary

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

2

. 0 l-IED Recomm e ndation s

............ ................ ... .. ........................ ... .. .. . .. ...... . .......... . .. . .. .. . .. . .. ..... 4

2. 1 Toleran ce Considerations

..................................................................................................... 4

2.2 Label Considerations

......... ...... ... .. ................................ ..... .................................................. 4



### 3.0 Introduction

............ . ... . .. ............... .... . .............. ... . ................... ........................ ...................... 

### 4

3 .1 

### Chemica l Id entity and Physical / Chemical Character i stics

............................................... 

### 4


### 3.2 Pesticide Use Panern and Anticipated Exposure Pathways

............................................. 

### 5

3.3 Considerat i on of Environmenta l Justice

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


### 4.0 Hazard Id en tifi cation/Tox i cology

......... ................ ................... .. .. ......... .. . ....................... ...... 

### 6

4.1 

### Summary of Tox ic olog ical Effec t s

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



### 4.2 Safety Factor for Infants and Children (FQPA Safety Factor)

......................................... 

### 7

4.3 Toxicity Endpo int and Point of Dep ar tur e Se lection s

...................................................... 

### 7

4.4 

### Endocrine Disruptor Screening Pro gram

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


### 5.0 Dietary Exposure and Risk Assessment

..................... .............. .......................................... 

### I 0

5.1 Residue Profile

............................................................................................................... 

### I 0



### 5.2 Water Residue Profile

.................................................................................................... 10



### 5

. 3 Dietary Risk Assessment..

.. ................................ ........... .............................. ........... ........ 11

6.0 Residential (Non-Occupational) Exposure/Risk C haracteri zation

.................................... 12


### 6.1 Spray Drift

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

7.0 Aggregate Exposure/Risk Characterization

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

8.0 Cumulative Ex po sure / Risk Characterization

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

### 9.0 Occupational Exposure / Risk Characterization

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

9 

### .1 Occupational Handler Exposure/Risk Estimates

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



### I 

### 0.0 Public H ealth a nd Pesticide Epidemiology Data

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

11.0 R efere nc es

.................................................................................................. .................. ..... 17 Appendix A. Toxicology Profile and Execu ti ve Summaries

.................................................... 

### 27 Appendix 

### B. Review of Human Re search

........................... .. ................................................... 

### 27 Appendix C. Occupational Non

- cancer H a ndl e r Algorithms

................................................... 27 Appe ndix D. Dietary Exposure/Risk Modeling Input a nd Output

........................................... 27 Appendix E. Nomenclature and Phy s ic al/Chemical Propertie s

............................................... 27 Appendix 

### F. Spray Drift Detailed Description

......................................................................... 

### 27 Appe ndi x G. Submitta l of Analyt i ca l Reference Standards (860.1650)

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

Pa ge 2 of32

### Page 3 of 32

1.0 Executive summary

Prosulfuron is a sulfonylurea herbicide that is used to control pre

- and post

- emergent broadleaf weeds in/on a variety of agricultural crops. It is currently registered for use in/on barley, field corn (grown for grain, silage, or seed), grain sorghum (milo), oats, popcorn, proso millet, rye

, triticale , wheat , and following small grain harvest. This document addresses exposures and risk
estimates fr om the registered uses of prosulfuron required during Registration Review.

There are several end

- use product labels registered with prosulfuron as the active ingredient.
These include water

- dispersible granules in water

- soluble packet (WSP) formulatio ns. The registered products are applied either with aerial or groundboom equipment. The single application rate of the registered uses for prosulfuron range from 0.02 to 0.0356 lb ai/A. Based on the registered use pattern for prosulfuron, short

- and int ermediate

- term inhalation and dermal exposures are anticipated for occupational handlers. In terms of personal protective equipment (PPE), the prosulfuron labels require handlers to wear baseline attire (i.e., long sleeved shirt, long pants, shoes plus so cks) and chemical

- resistant gloves.

The tox icology database for prosulf uron is adequate for risk assessment. Immunotoxicity and
subchronic inhalation toxicity studies have been waived for prosulfuron by the Hazard and Science Policy Council (HASPOC)

. T he last human health risk assessment for prosulfuron was completed in 2009 and a human health scoping document was issued in 2012 . Since then, n o new toxicity and/or metabolism data have been received . For this assessment, t he toxicological endpoints and points of departure (PODs) have been updated to include an incidental oral POD in order to assess exposure from spray drift . All other endpoints/PODs selected for risk assessment remain the same as in the previous assessment s

.

The existing residue che mistry database for prosulfuron is complete and adequate for risk assessment purposes. No additional residue chemistry data are required at this time. HED has
conducted a cute and chronic dietary exposure and risk assessment s for prosulfuron using
toleran ce

- level residues in foods and estimated drinking water concentrations (EDWCs) provided by the Environmental Fate and Effects Division (EFED). Acute and c hronic dietary exposure and risk estimates (food and drinking water) are not of concern for the gener al U.S. population or any other population subgroup . Prosulfuron is classified as, “not likely to be carcinogenic to humans”; therefore, a cancer dietary assessment was not conducted for prosulfuron.

There are no proposed or cur rent registrations for p roducts containing prosulfuron that allow residential use. Therefore, residential handler and conventional residential post

- application exposure assessments were not conducted to support Registration Review. A quantitative spray
drift assessment was cond ucted. Risk estimates from groundboom and aerial applications are not of concern from the field edge for all scenarios considered.

In the case of prosulfuron, aggregate exposure and risk estimates are equivalent to the dietary (food and water) exposure a nd risk estimates and are below HED’s level of concern.

The occupational handler exposure and risk estimates based on the highest application rate and
amount handled scenario indicate that the short

- and intermediate

- term inhalation MOEs are not

### Page 4 of 32

of concer n to HED (i.e., MOEs ≥ 100). The inhalation MOEs ranged from 41,000 to 2,000,000. Occupational post

- application dermal exposure was not quantitatively assessed since there is n o dermal hazard for prosulfuron. Based on the Agency's current practices, a q uantitative non

cancer occupational post

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

- appl ication inhalation expo sure assessment for prosulfuron

. The restricted entry interval ( REI ) of 12 hours specified on the registered labels is
based on the acu te toxicity of prosulfuron and is adequate

.

HED has not identified any risk concerns asso ciated with th e registered uses of prosulf uron. There are no data gaps that would require submission of additional toxicity or exposure data.

This risk assessment relies in part on data from studies in which adult human subjects were intentionally expose d to a pesticide or other chemi cal. For a list of data sources

, see A ppendix B.

2.0 HED Recommendations

2.1 Tolerance Considerations

The existing tolerances for residues of prosulfuron (40 CFR § 180. 481 ) are supported by the

av ailable residue chemis try data. Codex has not established maximum residue limits (MRLs) for
residues of prosulfuron . Canada has established MRLs for prosulfuron which are harmonized
with U.S. tolerances.

HED notes that the tolerance expression for prosulfuron in 40 CFR § 18 0.481 requires revision to state the following:

(a) General. Tolerances are established for residues of prosulfuron, including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified bel ow is to be determined by measuring only prosulfuron ( N

- [[(4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)amino]carbonyl]

- 2

- (3,3,3

- trifluoropropyl)benzenesulfonamide) in or on the commodity.

2 .2 La bel C onsiderations

There are no label recommendations for reg istered products containing prosulf uron.

3.0 Introduction

3.1 Chemical Identity and Physical/Chemical Characteristics

Prosulfuron

, ( N

- [[(4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)amino]carbonyl]

- 2

- (3,3,3

- trifluoropropyl)benzenesulfonamide)

, is a colorle ss, odorless, crystalline solid

. The chemical

prope rties of prosulf

uron do not suggest that there are any particular exposure issues that warrant special consideration

. The structure and physical/ch emical properties of prosulf uron are provided in Appendix E

.

### Page 5 of 32

3.2 Pesticide Use Pattern and Anticipated Exposure Pathways

Table 3.2 provides a summary of the highest application rate of the registered uses for prosulfuron

.

Table 3.2. Summary of Registered Uses of Prosulfuron.

Application Equipment Formulation Maximum Application
Rate REI Use Directions and
Limitations

Field Corn (grown for grain, silage, or seed), Grain Sorghum (Milo)

Aerial,
Groundboom Water

dispersible granule in

Water

Soluble
Packets 0.0356 lb ai/A 12 hours Do not apply this product

t hrough any type of irrigation system. Do not apply the product by aerial application in New York.

Rye, Oats, Proso Millet, Wheat, Barley, Popcorn, Triticale, Small Grains

Aerial,
Groundboom Water

dispersible granule in

Water

Soluble
Packets 0.02 lb ai/A 12 hours Do not apply this product through any type of irrigation system.



### Exposure Pathways

Indiv iduals may be exposed to prosulf uron via the ir diet (food and drinking water) . T here are no residential uses of prosulfuron

. However, there is the pote ntial for non

- occupational exposure as
a result of spray drift. Agricultural w orkers may be exposed to prosulfuron during mixing, loading, and/or applying the herbicide as well as during post

- application activities.

3.3 Consideration of Environmental Ju stice

Potential areas of environmental justice concerns, to the extent possible, were considered in the preliminary human health risk assessment for prosulf uron , in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Just ice in Minority Populations and

Low

- Income Populations," ( http://www.epa.gov/compliance/resources/policies/ej/exec_order_12898.pdf ) . As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups according
to well

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

### Page 6 of 32

exposure assessments are performed when conditions or cir cumstances 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. F urther 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
pattern s among specific subgroups.

4.0 Hazard Identification/Toxicology

The toxicology database for prosulfuron is complete and adequate for risk assessment.

I mmunotoxicity and subchronic inhalation studies are listed as part of the current 40 CFR Part
158 Toxicology Data Requirements. However, the Hazard and Science Policy Council (HASPOC) determined that these studies are not required at this time for prosulfuron ( Y. Yang,

TXR# 0056759 , 08 / 15/2013 and E. Craig, TXR#, 0052986, 05/07 2015 ). The TOXLINE (Nati onal Library of Medicine) database literature search did not identify any new toxicological information not already considered. The latest risk assessment was conducted in 2009 (B. Hanson, D 370557

, 10/20/2009). For a summary of the acute, subchronic and c hroni c toxicity profile, see Appendix A

.

4.1 Summary of Toxicological Effects

The most prevalent effect observed across species and study durations following administration of prosulfuron was decreased body weight ; observed in subchronic and chronic ora l toxicity
studies in rats and dogs. Additionally, s ubchronic and chronic oral toxicity studies in dogs
showed decreased hematological parameters and hepatic toxicity

. Evidence of neurotoxicity was observed in an acute neurotoxicity study but not in the subchronic neurotoxicity study. The neurological effects seen in the acute neurotoxicity study were transient, affecting primary sensorimotor and gait functions. In a developmental range

- finding study in rabbits, ataxia, hypoactivity, and neuropathology were observed starting at doses of 150 mg/kg/day. However, these potential signs of neurotoxicity were not consistent with findings in the two main developmental studies in rabbits where there were no signs of neurotoxicity observed up to 200 mg/kg/day. Additionally, o ther repeated dosing studies in the rat, mouse and dog did not show evidence of neurotoxicity. There is no evidence that prosulfuron is an immunotoxic chemical

. In accordance with the 2005 Guidelines for Carcinogen Risk Assessment, prosulf uron is
classified as “

Not Likely to Be Carcinogenic to Humans” based on the lack of evidence of carcinogenicity in mice and rats and no concern for mutagenicity. Prosulfuron has low acute toxicity by the oral, dermal, and inhalation routes of exposure , it is not considered an eye or skin
irritant and it is not a skin sensitizer

.

T here was no evidence from the developmental and reproductive studies of increased susceptibility in rat or rabbit fetuses. In the first of t wo rabbit developmental studies, ther e were no signs of mate rnal or developmental toxicity . The second rabbit (tested using higher doses than the first) and the rat developmental studies showed dose

- related increases in small fetuses and
skeletal effects but these occurred at maternal ly toxic doses

. In the reproductive study in rats,

### Page 7 of 32

d ecreases in body weights were noted for both the adults of the P 0 

### and P 1 

### generations and for the

F 1 

### and F 2 

### pups.

With oral administration in rats , approximately 90% of the administered dose was excreted during the first 48 hours. No information regarding absorption was provided in metabolism
studies. At higher doses a greater proportion of the administered dose was excreted in the feces compared to urine. Females usually excreted more of the dose in the urine t han males in both instances. The major routes of metabolism occurred via hydroxylation at side chains and phenyl ring positions, and O

- demethylation of the triazyl methoxy group or O

- demethylation of the methoxy group, and hydroxylation of the triazinyl m ethyl group. Minor routes of metabolism included unsaturation of the trifluoropropyl side chain, hydrolysis of the phenyl

- sulfonylurea link, and oxidative/hydrolytic cleavage of the triazine ring system.

4.2 Safe ty Factor for Infants and Children (FQPA Safety Factor)

The toxicity database of prosulfuron is complete and adequate to assess susceptibility in the

young . T here is no evidence of increased qualitative or quantitative susceptibility and exposure estimates are unlikely to underestimate risk.

. Although there was e vidence of neurotoxicity in the acute neurotoxicity study and the range

- finding developmental toxicity rabbit study (see Section 4.1) , the selected endpoints are protective of these effects since they were seen at dose levels in

excess of those where systemic toxicity occurred and at doses at least 15

- fold higher than the no

observed adverse effect levels ( NOAELs ) selected for risk assessment. Concern is also low since no neurotoxicity was observed in the rest of the prosulfuron toxicolo gical database, including the subchronic neurotoxicity study in rats

. . Therefore, the 10

- fold FQPA Safety Factor is reduced to

1 x

.

4 .3 Toxicity Endpoint and Point of Departure Selections

There have been no changes to selected endpoints since the last r isk assessment, except the subchronic oral toxicity study in dogs was also selected to assess incidental oral exposures. The study is appropriate for the route and duration of exposure for incidental oral assessment and considered protective of the popula tion of concern given that there was no evidence of offspring susceptibility in the toxicological database.

It is recognized that the studies in the toxicological database for prosulfuron, including those used for endpoint selection, have not been updated to reflect current policy and ma y be considered conservative. However, t he current PODs are protective of the effects observed in the prosulfuron database and any updates would not impact the overall findings of the risk assessment given the current risk picture for prosulfuron.

Table 4.3.1

. Prosulfuron Summary of Toxicological Doses and Endpoints for Use in Dietary Human Health Risk Assessments.

Exposure
Scenario Point of

Departure Uncertainty/

FQPA SFs Population Adjusted

Dose for Risk

Assessment St udy and Toxicological Effects

### Page 8 of 32

Exposure
Scenario Point of

Departure Uncertainty/

FQPA SFs Population Adjusted

Dose for Risk

Assessment St udy and Toxicological Effects

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

- 49 years of age) NOAEL = 10

mg/kg /day UF A = 10x

UF H =10x FQPA SF= 1x Acute RfD = 0.1

mg/kg/day
aPAD = 0.1 mg/kg/day Acute Neurotoxicity Study

– R at

MIRD 43387703 LOAEL = 250 mg/kg/day, based on abnormal gait in females.

Chronic Dietary (All Populations) NOAEL= 5.3

mg/kg/day UF A = 10x

UF H =10x FQPA SF= 1x Chronic RfD = 0.053

mg/kg/day
cPAD = 0.053 mg/kg/day Subchronic Oral Toxicity Study

– Dog

MI RD 42685230 LOAEL = 54 mg/kg/day, based on
decreased feed efficiency, hematological findings and hepatotoxicity in both sexes

.

Incidental oral (short

- &
intermediate

term) NOAEL= 5.3

mg/kg/day UF A = 10x

UF H =10x FQPA SF= 1x Residential LOC for

MOE = 100 Subchronic Oral Toxicity Study

– Dog

MIRD 42685230 LOAEL = 54 mg/kg/day, based on
decreased feed efficiency, hematological findings and hepatotoxicity in both sexes

. Dermal exposure (all durations) Not required based on the fact that no hazard was identif ied in the dermal study at dose levels as high as the limit dose (1000 mg/kg/day) and there is no evidence of quantitative offspring susceptibility

Inhalation

exposure Short

- (1

- 30 days),
Intermed iate (1

- 6 months) and Long

- Term (> 6 months) Oral

NOAEL = 5.3 mg/kg/day UF A = 10x

UF H =10x FQPA SF= 1x
IA = 100% Residential LOC for

MOE = 100 Subchronic Oral Toxicity Study

– Dog

MIRD 42685230 LOAEL = 54 mg/kg/day, based on
decreased feed efficiency, hematological findings and hepatotoxicity in both sexes

. C ancer (oral, dermal, inhalation) Prosulfuron is classified as “ Not Likely to Be Carcinogenic to Humans” based on the lack of

evidence of carcinogenicity in mice and rats and no concern for mutagenicity.

UF = uncertainty factor, FQPA SF = Special FQPA SF , NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose (a = acute, c = chronic) RfD = reference dose. MOE = margin of exposure. LOC = level of concern. IA = inhalation absorption factor.



### Table 4.3.2

. Prosulfuron Summary of Toxico logical Doses and Endpoints for Use in Occupational Human Health Risk Assessments

Exposure/
Scenario Point of

Departure Uncertainty

Factors Level of Concern for

Risk Assessment Study and Toxicological Effects

De rmal exposure (all durations) Not required based on the fact that no hazard was identified in the dermal study at dose

levels as high as the limit dose (1000 mg/kg/day).

### Page 9 of 32

Exposure/
Scenario Point of

Departure Uncertainty

Factors Level of Concern for

Risk Assessment Study and Toxicological Effects

Inhalation exposure
Short

- (1

- 30 days),
Intermed iate (1

- 6 months) and Long

Term (> 6 months) Oral

NOAEL = 5.3 mg/kg/day UF A = 10x

UF H =10x
IA = 100% Occupational LOC for

MOE = 100 Subchronic Oral Toxicity Study

– Dog

MIRD 42685230 LOAEL = 54 mg/kg/day, based

on decreased feed efficiency, hematological findings and hepatotoxicity in both sexes

. Cancer (oral, dermal, inhalation) Prosulfuron is classified as “ Not Likely to Be Carcinogenic to Humans” based on the lack of

evidence of carcinogenicity in mice and rats and no concern for mutagenicity.

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

po pulation (intraspecies) . MOE = margin of exposure. LOC = level o f concern . IA = inhalation absorption factor

.



### 4.4 Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these stu dies 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, in cluding 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
chro nic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its most recent registration decision for prosulfuron, EPA reviewed these data and selected the most sensitive endpoints for relevant risk ass essment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), prosulfuron is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whethe r 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 EDS P employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormon al
systems. C hemicals 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 ba sed on the available data. Tier 2 testing is designed to identify any adverse endocrine

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

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

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of

### Page 10 of 32

chemicals iden tified for EDSP screening was published on June 14, 2013 1 

### and includes some pesticides scheduled for Registration Review and chemicals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disruptors. For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website. 2



### 5.0 Dietary Exposure and Risk Assessment

5.1 Residue Profile

Th e existing residue chemistry database for prosulfuron is complete and adequate for risk assessment purposes. The qualitative nature of the residue of prosulfuron in plants is adequately understood based on acceptable metabolism studies and the most recent ly submitted rotational crop studies on root and leafy vegetables and small grains. The qualitative nature of the residues of prosulfuron in animals is adequately understood based on the available metabolism studies in ruminants and poultry. T here is no reasonable expectation of residues in livestock commodities (40CFR§ 180. 6(a)(3)). Adequate high

- performance liquid chromatography (HPLC) methods are available for enforcing tolerances for prosulfuron residues in plant commodities. Previous
residue chemist ry deficiencies have been resolved. No additional residue chemistry data are required at this time.

5.2 Water Residue Profile

Screening ground water

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

- GW; v.1.07) for use in the sulfonylurea (SU) dietary risk assessments. EFED initially provided coarse

- screen estimates that should exceed the upper

- bound chemical

- specific EDWCs for any SU; however, for several of the SUs,
the coarse

- screen ED WCs resulted in dietary risks of concern and EFED subsequently generated
refined

- screen EDWCs for these SUs. The application inputs for the refined

- screen EDWCs represent the maximum application rate pattern for the chemical, considering the maximum singl e application rate first, then the maximum seasonal application rate, using usage data provided by BEAD if the labels do not provide a maximum seasonal rate. The modeled sorption
coefficient is also chemical

- specific. All other inputs, including the scre ening assumptions of stability to degradation and application every year, remained the same as for the coarse screen. The resulting refined

- screen EDWCs from PRZM

- GW can be used as a conservative estimate of exposure and are summarized in Table 5. 2 ( G. Or rick, D427429, 08/12/2015 ).

The acute and chronic dietary assessments for prosulfuron used the refined

- screen maximum daily concentration of 15 μg/L (0.015 ppm) and the post

- breakthrough mean value of 13 μg/L (0.013 ppm), respectively.

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

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of
chemicals.

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

### Page 11 of 32

Table 5.2. PRZ M

- GW Refined

- Screen EDWCs for Sulfonylureas

Sulfonylurea (Use) PRZM

- GW
Scenario Max. Daily Conc. (μg/L) Post

- breakthrough Mean (μg/L) Mean

Breakthrough Time (years)

Chlorsulfuron (non

- ag areas) NC cotton 78 52 5.9

Halosulfuron

- methyl (fallow) NC cotton 74 53 8.1
Nicosulfuron (rights

- of

- way) NC cotton 39 26 6.2

Prosulfuron (corn) NC cotton 15 13 12

Rimsulfuron (commercial areas) NC cotton 105 71 6.5
Triasulfuron (rangeland) NC cotton 21 19 16

Tribenuron

- methyl (corn) NC cotton 35 23 6.1

Triflusulfur on

- methyl (sugarbeet) FL citrus 23 20 9.5



### 5 .3 Dietary Risk Assessment

HED has conducted acute and chronic dietary exposure and risk assessments for prosulfuron using tolerance

- level residues in foods and EDWCs provided by EFED. Exposure and risk
estima tes were obtained from the Dietary Exposure Evaluation Model using the Food Commodity Intake Database (DEEM

- FCID; version 3.18). The model uses food consumption
data from the 2003

- 2008 National Health and Nutrition Examination Survey/What We Eat in
Americ a (NHANES/WWEIA) database, coupled with recipe files and residues in foods, to derive estimates of dietary exposure and risk.

Generally, HED is concerned when dietary exposure estimates exceed 100% of the acute or chronic population adjusted dose (aPAD and cPAD , respectively ). Acute and chronic dietary risk estimates (food and drinking water) are not of concern for the general U.S. population or any other population subgroup (Table 5.3). At the 95th percentile of exposure, the acute exposure
estimate u tilized <1.0% of the aPAD for the general U.S. population and 2.6% of the aPAD for all infants (<1 year old), the most highly

- exposed population subgroup. The chronic exposure estimate utilized <1.0% of the cPAD for the general U.S. population and 1.4% of the cPAD for all infants (<1 year old), the most highly

- exposed population subgroup. Because of the very conservative assumptions used in the analysis (tolerance

- level residues, 100% crop treated,

upper

- bound modeled drinking water estimates), actual exp osure and risk s are expected to be much lower than those shown in Table 5.3. The listings of inputs and outputs to the assessment are included in Appendix D . Prosulfuron is classified as, “not likely to be carcinogenic to humans”; therefore, a cancer die tary assessment was not conducted for prosulfuron.

Table 5.3. Summary of Acute and Chronic Dietary Exposure (Food and Drinking Water) and Risk for
Prosulfuron 1

.

Population Subgroup Acute Dietary (95 th Percentile) Chronic Dietary

Dietary Exposure (mg /kg/day) % aPAD Dietary Exposure (mg/kg/day) % cPAD

General U.S. Population 0.000866 <1.0 0.000311 <1.0 All Infants (<1 year old) 0.002641 2.6 0.000756 1.4

Children 1

- 2 years old 0.001389 1.4 0.000483 <1.0

### Page 12 of 32

Table 5.3. Summary of Acute and Chronic Dietary Exposure (Food and Drinking Water) and Risk for
Prosulfuron 1

.

Population Subgroup Acute Dietary (95 th Percentile) Chronic Dietary

Dietary Exposure (mg /kg/day) % aPAD Dietary Exposure (mg/kg/day) % cPAD

Children 3

- 5 years old 0.001132 1.1 0.00 0422 <1.0

Children 6

- 12 years old 0.000863 <1.0 0.000306 <1.0

Youth 13

- 19 years old 0.000729 <1.0 0.000242 <1.0

Adults 20

- 49 years old 0.000838 <1.0 0.000305 <1.0

Adults 50

- 99 years old 0.000742 <1.0 0.000292 <1.0

Females 13

- 49 years old 0.000853 <1.0 0.000302 <1.0

1 Population with the greatest exposure is in bold. Exposure and risk estimates calculated using DEEM version 3.18.



### 6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

There are no proposed or registered products containing pro sulfuron that would result in residential exposure. Therefore, a quantitative residential exposure and risk assessment was not performed. However, prosulfuron can be applied via ground and aerial equipment, t herefore, a quantitative assessment was conduc ted to address any potential indirect exposures to prosulfuron

as a result of spray drift.

6.1 Spray Drift

A detailed description about HED’s spray drift policy and how to evaluate the drift potential and associated risks is available in Appendix F.

6 .1. 1 Combined Risk Estimates from Lawn Deposition Adjacent to Applications

The spray drift risk estimates are based on an estimated deposited residue concentration as a result of the screening level agricultural application scenarios. Prosulfuron is used on field corn, popcorn, grain sorghum (milo), wheat, barley, rye, oats, triticale, proso millet, and small grain harvest and can be applied via groundboom and aerial equipment. The spray drift assessment was conducted using the highest registered applica tion rate of 0.0356 lb ai/acre for use on field corn. The recommended drift scenario screening level options are listed below:

 Groundboom applications are based on the AgDrift ® 

### option for high boom height and using very fine to fine spray type using the 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). 3

3 AgDrift ® allows for consideration of even finer spray patterns characterized as very fine to fine. However, this spray pattern was not selected as the common screening basis since it is used less commonly for most agriculture. If assessors identify this use pattern, then it should be used as the screening criteria and deposition values associated
wit h it ae provided in Table 1 below. Justification for including this spray quality should be included in any assessment based on specific label directions for its use.

### Page 13 of 32

There are no short

- or intermediate

- term dermal PODs. Only incidental oral risk estimates were evaluated. The total applicable LOC is 100, so MOEs <100 would be of concern. Children (1 to <2 yea rs old) incidental oral risk estimates from exposure to prosulfuron related to spray drift result in no risks of concern at the field edge for either groundboom or for aerial applications ( Table 6.1.1. ).

6.2 Residential Bystander Post

- Application Inhalation Exposure

Volatilization of pesticides may be a source of post

- application inhalation exposure to individuals nearby pesticide applicat ions. The agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on
March 2 , 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis (http://www.regulations.gov/#!docketDeta il;D=EPA

- HQ

- OPP

- 2014

- 0219).

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 required for prosulfuron.

7.0 Aggregate Exposure /Risk Characterization

The Food Quality Protection Act of 1996 directs EPA to assess aggregate exposure to pesticide chemical residues, including all anticipated dietary exposures and all other exposures for which
there is reliable informat ion. In the ca se of prosulf uron, aggregate exposure and risk estimates are equivalent to the dietary (food and water) exposure and risk estimates in Section 5, above,
and are below HED’s level of concern.

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 [ http://www.epa.gov/oppfead1/cb/csb_page/updates/2015/framework

- for

- screening

analysis.html ]. This document provides guida nce on how to screen groups of pesticides for Table 6.1.1. Children (1 to <2 years old) Inciden tal Oral Risk Estimates (MOEs) Related to Spray Drift Exposure for Flurprimidol.

Crop/Rate Group Spray Type/Nozzle Configuration Application
Rate (lb ai/A) Estimated

TTR t (ug/cm2) At Edge

HtM MOE

Field Corn

Aerial Fine to Medium 0.0356 0.00395694 3 8,000

Groundboom High Boom Very fine to Fine 52,000

### Page 14 of 32

cumulative evaluation using a two

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

- based screening approach. This framework supplements th e existing guidance documents for establishing common mechanism groups (CMGs) [1] 

### and conducting cumulative risk assessments (CRA) [2]



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

necessary.

9.0 Occupational Exposure/Risk Characterization

9.1 Occupational Handler Exposure/Risk Estimates

Based on current labeling, types of equipment and techniques that can potentially be used, occupational exposure associated with handler activi ties (i.e., mixing, loading, and applying) is expected from the registered use on field corn (grown for grain, silage, or seed), popcorn, grain sorghum (milo), wheat, barley, rye, oats, triticale, proso millet, and following small grain
harvest. The quant itative exposure/risk assessment developed for occupational handlers is based
on the scenarios listed in Table 9.1. Based on the use patterns (i.e., 1 application per season) and resistance management practices, occupational exposure f rom the registered food uses is expected to be short

- term (1

- 30 days) and i ntermediate

- term (1

- 6 months) and in duration.

L ong

- term exposures (greater than 6 months) are not anticipated. The registered labels require
handlers to wear baseline attire and chemical resistant gloves.

Occupational Handler Exposure Data and Assumptions

Application Rate : The highest application rate of the registered uses for prosulfuron is listed in
Table 3.2.

Unit Exposures: It is the policy of HED to use the best available data to assess handler exposure. Sources of generic handler data, used as surrogate data in the absence of chemical

- specific data, include PHED 1.1, the AHETF database, the Outdoor Residential Exposure Task Force (ORETF) database, or other registrant

- submitted occupatio nal exposure studies. Some of these data are proprietary (e.g., AHETF data), and subject to the data protection provisions of FIFRA. The standard values recommended for use in predicting handler exposure that are used in this assessment, known as “unit e xposures”, are outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table 4 

### ”, which, along with additional information on HED policy

[1] 

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

[2] 

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

4 Available: http://www.epa.gov/opp00001/science/handler

- exposure

- table.pdf

### Page 15 of 32

on use of surrogate data, including descriptions of the various sources, can be found at the Ag ency website 5



### .

Area Treated or Amount Handled : The area treated or amount handled is based on HED ExpoSAC Policy No. 9.1. Refer to Table 9.1. or these assumptions for each scenario.

Risk Estimate Equations : The algorithms used to estimate non

- cancer exposure and dose for occupational han dlers can be found in Appendix C

.

Combining Exposures/Risk Estimates:

The dermal route of exposure does not need to be combined with the assessed inhalation route of

exposure because there is no identified systemic dermal hazard.

Summary of Occupational Handler Non

- Cancer Exposure and Risk Estimates

The short

- and intermediate

- term inhalation risk estimates for the occupational handlers are greater than HED’s LOC (i.e., MOEs ≥ 100) at baseline for all scenarios, wi th MOEs ranging from 41,000 to 2,000,000. Table 9.1 provides the worst

- case scenarios for the registered uses for prosulfuron.

1 “High

- acreage field crops” include field corn. The worst

- case scenarios for the registered uses for prosulfuron are listed in this table.

2 “Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table ”; Level of mitigation = Baseline except for aerial applicator which includes engineering controls (EC).
3 Based on the currently registered labels (See Table 4.1).
4 Exposure Sci ence Advisory Council Policy #9.1.

5 Available: http://www.epa.gov/pes ticides/science/handler

- exposure

- data.html Table 9.1. Occupational Short

- and Intermediate

- Term Handler Exposure and Risk Estimates for
Prosulfuron.

Exposure Scenario C rop or Target 1 Inhalation
Unit Exposure 2 μg/lb ai (unless
otherwise indicated) Maximum

Application

Rate 3 Area

Treated or
Amount
Handled Daily 4 Inhalation

Dose 5 mg/kg/day MOE 6

LOC = 100

Mixer/Loader
M/L water dispersible granule in

water

- soluble p acket for aerial application High

- acreage field crops 0.24 (EC) 0.0356 lb

ai/A 1,200

acres 0.000129 41,000

M/L water

- dispersible granule in

water

- soluble packet for groundboom application High

- acreage field crops 0.24 (EC) 0.0356 lb

ai/A 200

acres 0.000 0214 250,000

Applicator
Applying sprays for aerial application High

- acreage field crops 0.0049 (EC) 0.0356 lb

ai/A 1,200

acres 0.00000261 2,000,000

Applying sprays for groundboom

application High

- acreage field crops 0.34 0.0356 lb
ai/A 200

acres 0.0000 303 170,000

Flagger

Flagger High

- acreage field crops 0.35 0.0356 lb
ai/A 350

acres 0.0000545 97,000

### Page 16 of 32

5 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 Daily (A or gal/day) ÷ BW (80 kg).

6 Short

- and Intermedia te

- term Inhalation MOE = Inhalation NOAEL (5.3 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).



### 9.2 Occupational Post

- application Exposure/Risk Estimates

9 .2.1 Occupational Post

- application Inhalation Exposure/Risk Estimates

There are multiple potential sourc es of post

- application inhalation exposure to individuals performing post

- application activities in previously treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticide s. The agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2 010 ( http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html ). The agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis ( http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

OPP

- 2014

- 0219 ). During Registration Review, the agency will utilize this analysis to determine if data (i.e., flux studies, route

- specific inhalation toxicologi cal studies) or f urther analysis is required for prosulfuron

.

In addition, the Agency is continuing to evaluate the available post

- application inhalation exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the Agency will continue to identify the need for and, subsequently, the way to incorporate occupational post

- application inhalation exposure into the A gency's risk assessments.

Although a quantitative occupational post

- application inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercial handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in higher exposure than post

- application exposure. Therefore, it is expected that these handler inhalation exposure estimates would be protective of most occupational post

- application inhalation exposure scenarios.

9.2.2 Occupational Post

- application Dermal Exposure/Risk Estimates

Occupational post

- application dermal exposure was not quantitatively assessed for prosulfuron since there is no dermal hazard for prosulfuron.

Dislodgeable Foliar Residue (DFR): In accordance with the updated Part 158 data requirements (2007), one or more DFR studies are required when a p esticide has residential or occupational uses that could result in post

- application dermal exposure. Since there is no hazard via the dermal route of exposure, a non

- cancer dermal post

- application risk assessment was not performed for prosulfuron . Theref ore, DFR studies are not needed for prosulfuron at this time. If the PODs change, the need for DFR studies may be reevaluated in the future to refine the post

application assessment.

Restricted Entry Interval

### Page 17 of 32

The REI specified on the proposed label is b ased on the acute toxicity of prosulfuron. Prosulfuron is classified as Toxicity Category III via the dermal route and Toxicity Category IV for skin irritation potential. It is not a skin sensitizer. Under 40 CFR 156.208 (c) (2) (iii), ai’s
classified as Acute III or IV for acute dermal, eye irritation and primary skin irritation are assigned a 12

- hour REI. Therefore, the [156 subpart K] Worker Protection Statement interim REI of 12 hours is adequate to protect agricultural workers from post

- application exposures to prosulfuron.

10.0 Public Health and Pesticide Epidemiology Data

The OPP Incident Data System (IDS)

, the Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event Notificat ion System for Occupational Risk

- Pesticides (SENSOR) databases were consulted for pesticide incident data on the active ingredient prosulfuron in 2012 and no incidents of concern were identified (S. Recore, D 397848 , 02/04/2012) ; therefore additional analys is is not required

. Prosulfuron is not included in the Agricultural Health Study (AHS), and therefore this study does not provide
informat ion for this report . The Agency will continue to monitor the incident information and if a concern is triggered, add itional analysis will be included in the risk assessment.

11.0 References

Open literature references

A literature search was performed for prosulf uron . The search did not reveal information that would impact the current risk assessment.

Internal m emos

Author Barcode Date Title
M. Hawkins

, Y. Barnes

, S. Dapson D396736 4/17/2012 Prosulfuron: Registration Review Scoping Document for Human
Health Assessments

.

S. Recore D 397848 2/14/2012 Prosulf uron : Review of Human Incidents

B Hanson D370557 10/2 0/2009 Prosulfuron. REVISED Human Health Risk Assessment for the Proposed Establishment of Permanent Tolerances for Uses in/on Cereal Grains (Crop Group 15), Except Rice.

G. Orrick D427429 08/12/2015 Drinking Water Exposure Assessment for the Registratio n Review of 22 Sulfonylurea Herbicides

### Page 18 of 32

Appendix A. Toxicology Profile and Executive Summaries

A.1. Toxicology Data Requirements

Table A.1. Prosulfuron Data Requirements

Test Technical

Required Satisfied

870.1100 Acute Oral Toxicity

................................ ...................... 870.1200 Acut e 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 Sub chronic (nonrodent)

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

- Day Dermal

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

- Day Dermal

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

- Day Inhalation

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

yes

yes

no

yes yes

yes

yes

--- Waived 1

870.3700 Developmental Toxicity (rodent)

................................ . 870.3700 Developmental Toxicity (nonrodent)

........................... 870.3800 Reproduction

................................ ................................ ye s
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 Chronic Toxicity/Carcinogenicity (rodent)

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

yes

yes

yes
yes yes

yes

yes

yes
yes

870.5100 Mutagenicity

— Gene Mutation

- bacterial

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

— Gene Mutation

- mammalian

............... 870.5375 Mutagenicity

— Structural Chromosomal Aberrations

.. 870.5385 Mutagenicity

— Structural Chromosomal Aberrations

.. 870.5395 Mutagenicity

— Other Genotoxic Effects

...................... 870.5550 Mutagenicity

— Other Genotoxic Effects

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

yes

yes

yes

yes

yes yes

yes

yes

yes

yes

yes

870.6100 Acute Delayed Neurotox. (hen)

................................ .... 870.6100 90

- Day Neurotoxicity (hen)

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

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

- Day Neuro toxicity Screening Battery (rat)

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

................................ ...... no

no

yes

yes

no ---

--- yes

yes

---

870.7485 General Metabolism

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

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

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

no

yes yes

--- Waived 2

1 Data requirement waived by HA SPOC for t he inhalation study ( E. Craig

, TXR# 0052986 )

. 2 Data requirement waived by HASPOC for t he immunotoxicity study ( Y. Yang, TXR# 0056759)

.

### Page 19 of 32

A.2. Toxicity Profiles

Table A.2.2. Prosulfuron Subchronic, Chronic and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/ Classification
/D oses Results

870.3100 90

- Day oral

toxicity

- rats 42685232 (1991)

Acceptable/guideline

Dietary levels of 0, 5, 50, 500, 4,000 or 8,000 ppm

( 0, 0.31, 3.1, 31, 255, or 522 mg/kg/day for males and 0, 0.32, 3.4, 35, 268, or 512 mg/kg/day for females) NOAE L = 50 ppm (3.1 mg/kg/day) for males and 500 ppm (35 mg/kg/day) for females.

LOAEL = 500 ppm (31 mg/kg/day) for males, based on reduced body weight and body weight gain (13%); and 4,000 ppm (268 mg/kg/day) for females, based on reduced body weight, body w eight gain, food consumption, and food efficiency.

870.3100 90

- Day feeding

-

mouse 42685234 (1991)

Core minimum

Dietary levels of 0, 15, 500, 1750, 3500, or 7000 ppm. Mean daily doses were 0, 2.0, 69.3, 234, 504, 969 mg/kg/day for males and 0, 2.9, 91.3, 293, 606, and 1400 mg/kg/day for females. The NOAEL = 15 ppm (2.0 mg/kg/day) for males; 500 ppm (91.3 mg/kg/day) for
females.

LOAEL = 500 ppm (69.3 mg/kg/day) for males, based on statistically significant
decreased albumin and total bilirubin and

s tatistically significant increased absolute and relative liver (to brain and/or body) weights. The LOAEL is 1750 ppm (293 mg/kg/day) 

### Table A.2.1. Acute Toxicity of Prosulfuron Technical

Guideline No. Study Type MRID # Results Toxicity Category

870.1100 Acute Oral 42685215 LD 50 = 986 mg/kg III

870.1200 Acute Dermal 42685216 LD 50 > 2000 mg/kg III

870.1300 Acute Inhalation 42685217 LC 50 = 5.467 mg/L IV

870.2400 Primary Eye

Irritation 42685218 Minimal irritant IV

87 0.2500 Primary Skin

Irritation 42685219 Non

- irritant IV

870.2600 Dermal

Sensitization 42685220 Non

- sensitizer N/A

### Page 20 of 32

Table A.2.2. Prosulfuron Subchronic, Chronic and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/ Classification
/D oses Results

for females, based on statistically significant increased relative liver (to brain and body) weights, statistically signifi cant increased hematocrit and mean corpuscular volume, and decreased mean corpuscular hemoglobin
concentration.

870.3150 90

- Day feeding

–

dog. 42685230 (1992)

Acceptable/guideline

via the diet at dose levels of 0, 15, 150, 1500, or 3000 ppm for 90 day s. The equivalent average daily intake of test material was 0, 0.54, 5.3, 57, or 110 mg/kg/day (males) and 0, 0.59, 6.5, 54, or 120 mg/kg/day (females). NOAEL = 150 ppm (5.3 mg/kg/day) for
males and females

LOAEL = 1500 ppm (54 mg/kg/day) based
on decre ased bodyweight gain and feed efficiency as well as hematological and hepatic toxicity in both males and females.

870.3200 21

- day dermal

toxicity study

- rabbits 42685235 (1992)

Acceptable/guideline

Doses of 0, 10, 100, 500 or 1,000 mg/kg/day CGA

- 15200 5 Technical, were applied to the clipped backs of Chbb:NZW rabbits for 6 hours/day, 7 days/week, for 3 weeks. Systemic NOAEL = 1000 mg/kg/day

Systemic LOAEL = Not established.
There was increased absolute and relative liver weights in both sexes at 500 a nd 1000 mg/kg/day. However, these findings were not considered sufficient to establish a systemic toxicity LOAEL. The increased liver weights, however, were considered indicative of dermal absorption of CGA

- 152005.

Dermal NOAEL = 1000 mg/kg/day, based on the absence of any significant dermal or systemic effects at the highest dose tested.

Dermal LOAEL = Not determined.

870.3250 90

- Day dermal

toxicity No study available and not required at this time.

870.3465 90

- Day

inhalation toxicity No study a vailable but requirement waived at this time.

870.3700 Prenatal

developmental

- rats. 42685237 (1992)

Acceptable/guideline

Sprague Dawley rats received either 0, 5, 50, 200 or 400 mg of
CGA

- 152005/kg/day by gavage (technical, 96% a.i.), from gestati on days 6 through 15, Maternal toxicity NOAEL = 200 mg/kg/day

Maternal toxicity LOAEL = 400 mg/kg/day (highest dose level tested), based on decreased body weight gain.

Developmental toxicity NOAEL = 200 mg/kg/day.

Developmental toxicity LOAEL = 4 00

### Page 21 of 32

Table A.2.2. Prosulfuron Subchronic, Chronic and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/ Classification
/D oses Results

inclusive mg/kg/day based on skeletal findings (increase in findings of 14th ribs).

870.3700 Prenatal

developmental

- rabbits

Range finding 42685238 (1991)

Supplementary

New Zealand White rabbits
received 150, 300, 450, or 600 mg/kg/day by gavage (96% a.i.), from gestation days 7 through 19. Signs of neurotoxicity (ataxia, hypoactivity, and neuropathology) were observed star t ing at the lowest dose tested (150 mg/kg/day).

Developmental toxicity was apparent (increased incidence of resorptions and abortions) sta rting at doses of 300 mg/kg/day.

870.3700 Prenatal

developmental

- rabbits 42685239 (1992)

43159318 (1994)

Supplementary

New Zealand White rabbits receive either 0, 1, 10, or 100 mg
of CGA

- 152005/kg/day by gavage (96% a.i.), from gestation days 7
thro ugh 19, inclusive. Maternal toxicity NOAEL = 100 mg/kg/day (HDT)

Maternal toxicity LOAEL = not established

Developmental toxicity NOAEL = 100 mg/kg/day (HDT)

Developmental toxicity LOAEL = not
established

No effects were noted at the highest dose
level t ested, 100 mg/kg/day, but this should
not be considered a definitive NOAEL since the maternal animals were not adequately challenged, and a limit dose was not utilized in this study.

870.3700 Prenatal

developmental

- rabbits 43953506 (1996)

Acceptable/g uideline

New Zealand White rabbits received dosages of CGA

- 152005 technical (96% a.i.) by gavage at dose levels of 0, 20, 100 and 200 mg/kg/day on gestation days 7 to
19. Maternal toxicity NOAEL= 20 mg/kg/day

Maternal toxicity LOAEL = 100 mg/kg/day
based o n increases in abortion, decreases in food consumption, and in mean body weight gain.

Developmental toxicity NOAEL = 100 mg/kg/day

Developmental toxicity LOAEL = 200 mg/kg/day, b ased on a dose

- related increase
in runts and small fetuses as well as skeletal
effects.

870.3800 Multigeneration

Reproduction

- rat 43159319 (1993)

43159320 (1994) 43387707 (1994)

Core minimum

Sprague

- Dawley rats received either 0, 10, 200, 2000, or 4000 ppm (0, 0.67, 13.3, 136, and 278 mg/kg/day for P0 males and 0, 0.76, 1 5.3, 152, and~3l1 Parental toxicity NOAEL = 200 ppm (13.3 mg/kg/day for males and 15.3 mg/kg/day for females).

Parental toxicity LOA EL = 2000 ppm (136 mg/kg/day for males and 152 mg/kg/day for females), based upon decreased mean body weights and body weight gain observed in the P0 and P1 generation animals.

Reproductive toxicity NOAEL = 200 ppm

### Page 22 of 32

Table A.2.2. Prosulfuron Subchronic, Chronic and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/ Classification
/D oses Results

mg/kg/day for P0 females during the premating growth periods, respectively) of CGA

- 152005 (99.1% a.i.) mixed in the feed. (13.3 mg/kg/day for males and 15.3 mg/k g/day for females).

Reproductive toxicity LOAEL = 2000 ppm (136 mg/kg/day for males and 152 mg/kg/day for females), based upon decreased pup weights observed in both the Fl and F2 offspring.

870.4100 Chronic toxicity

rodents Refer to 870.4300 rat chro nic feeding/carcinogenicity study below

870.4100 Chronic toxicity

dogs.

1

- year 43159314 (1993)

43387705 (1994)

Acceptable/guideline

Diet concentrations at 0, 10, 60, 600 or 1200 ppm (0.3, 2.0, 18.6 or 41.0 mg/kg/day, males and 0, 0.3, 1.8, 20.2 or 48.8 mg/kg/day, females). mg/kg/day. NOAEL = 60 ppm (1.8 mg/kg/day, females).

LOAEL = 600 ppm (18.6 mg/kg/day, males), based on hematologic and clinical chemistry effects (females) and incidence of lipofuscin accumulation in liver (both sexes).

870.4200 Car cinogenicity

mice.

18

- months 43159316 (1993)

43387706 (1994)

Acceptable/guideline

(Crl:CD

- (ICR)BR), mice were admin 0, 15, 700, 3500 or 7000 ppm of CGA

- 152005 technical in the diet. Compound consumption was: 0, 1.71, 81.4, 410 and 832 mg/kg/day in males ; 0, 2.11, 100, 508, and 1062 mg/kg/day in
females. Systemic toxicity NOAEL = 700 ppm (81.4 mg/kg/day in males and 100 mg/kg/day in females).

Systemic toxicity LOAEL = 3500 ppm (410 mg/kg/day in males and 508 mg/kg/day in females), based on slightly decrea sed body weight gain in females.

There appeared to be no increase in the incidence of neoplasia in treatment groups when compared to controls.

870.4300 Combined

chronic feeding
and carcinogenicity study

- rats

2

- years 42700003 (1992)

43159321 (1994)

Core Minimum

(CrL:CD(SD)BR), rats were administered 0,10, 200, 2000 or 4000 ppm (0.4, 7.9, 79.9 and 160.9 mg/kg/day for males and 0.5, 9.2, 95.7 and 205.8 mg/kg/day for females, respectively) of technical CGA

152005 (a.i. 99.1%) in the diet. Systemic NOA EL = 200 ppm (7.9 mg/kg/day, males and 9.2 mg/kg/day, females).

Systemic LOAEL = 2000 ppm (79.9 mg/kg/day, males and 95.7 mg/kg/day, females), based on decreased body weight and body weight gain during the first months to 1 year of the study, decreased fo od consumption (females), hematopoietic system effects (males), and possibly increased GGT with decreases in liver, kidney and adrenal weight (females).

Increases in the incidence of mammary
adenocarcinomas in females were observed at 2000 ppm (31.9%; p < 0.5) and 4000 ppm

### Page 23 of 32

Table A.2.2. Prosulfuron Subchronic, Chronic and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/ Classification
/D oses Results

(26.3%; NS) compared to controls (17.5%). Mammary gland adenomas were also slightly increased at 2000 ppm and 4000 ppm (4.3% and 2.5% vs. 0%, controls). Slight increases in the incidence of benign testicular interstitial cell tumors (sig nificant trend only) were also observed at 2000 ppm (8.6%) and 4000 ppm (5.0%) compared to controls (1.6%).

870.6200 Acute

neurotoxicity screening battery 43387703 (1994)

Core Minimum

Hsd:Sprague

- Dawley rats received 0, 10, 250, 500 or 1000 mg/kg/day of CGA

- 152005 (technical, 99.1% a.i.) by gavage in aqueous 3% corn starch/

- 0.5% Tween 80 (20 ml/kg). NOAEL = 10 mg/kg/day.

LOAEL = 250 mg/kg/day, based on reduced motor activity and body temperature in males and abnormal gait in females.

870.6200 Subchr onic

neurotoxicity screening battery

– 90 day 43387704 (1994)

Core Minimum

Rats were fed diets containing 0, 10, 200, 2500, 5000 (high dose, females only) or 10,000 (high dose, males only) ppm prosulfuron technical. The equivalent average daily test

mate rial intakes were 0, 0.6, 12.1, 147 or 628 mg/kg/day, males; 0, 0.6, 12.5, 157 or 313 mg/kg/day, females). Neurotoxicity NOAEL = 10,000 ppm (males) and 5000 ppm (females).

Neurotoxicity LOAEL = not determined

Systemic NOAEL = 200 ppm

Systemic LOAEL = 2500 ppm, based on slightly reduced body weight gain in males.

870.7485 Metabolism and

pharmacokinetics

- rat 43159326 (1993)

Acceptable/guideline

Rats were administered [phenyl

14C] prosulfuron as a single oral dose of 0.5 mg/kg, a single i.v.
dose of 0.5 mg/kg, a single oral dose of 400 mg/kg and a single oral dose of [phenyl

- 14C] prosulfuron following 14 days of repeated dosing with 0.5 mg/kg of nonlabeled compound. Approximately 90% of the administered dose was excreted during the first 48 hours. At 400 mg/kg, a greater proportion of the
administered dose was excreted in the feces (33

- 36%) compared to urine (61

- 71%). Females usually excreted more of the dose in the urine (79

- 91%) than males (66

- 79%). The parent compound represented 8

- 27% of the

tot al activity in the urine of females and 5

- 9% in males, whereas in the feces there was
10

- 16% of the parent compound in females
and 5

- 6% in males. Fifteen urinary
metabolites were determined and 13 similar
metabolites were confirmed in feces. Tissue
levels were low. No measurable amount of radioactivity was found in most tissues 168 hours post

- dosing in animals at 0.5 mg/kg.

### Page 24 of 32

Table A.2.2. Prosulfuron Subchronic, Chronic and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/ Classification
/D oses Results

The major routes of metabolism occurred via hydroxylation at side chains and phenyl ring of the trifluoropropyl side chain, hydrolysis of the phenyl

- sulfonylurea link and oxidative/hydrolytic cleavage of the triazine ring system. The major metabolite (47% to 60% of urinary radioactivity at 0.5 mg/kg) was formed by hydroxylation of the triazinyl methyl group. At the 0.5 mg/kg level,
metabo lism was not affected by route of
administration.

870.7485 Metabolism and

pharmacokinetics

- rat 43159322 (1992)

43159323 (1993)

Acceptable/guideline

Rats were administered [triazine

4

- 14C] prosulfuron as a single oral dose of 0.5 mg/kg, a single
i.v . dose of 0.5 mg/kg, a single oral dose of 400 mg/kg and a single oral dose of [triazine

- 4

- 14C] prosulfuron following 14 days of repeated dosing with 0.5 mg/kg of nonradiolabeled compound. Approximately 90% of the administered dose
was excreted within 48 h ours post

- dosing. Tissue radioactivity was low, less than 0.91%
of the administered dose. The metabolite profile for each sex was similar regardless of the route of administration. However, females tended to excrete more radioactivity
in the urine and les s in the feces than males. The metabolites in the greatest concentration in the urine were #2 (hydroxylation of triazinyl methyl group) and #11 (parent compound) along with #1 (O

- demethylated methoxy group) and #3 (hydroxylation of trifluoropropyl group). Females excreted more parent compound than males. Males excreted more of the hydroxylated
metabolites and more metabolites with a double bond on the trifluoropropyl group. Urinary metabolite #3 was greater at 400 mg/kg than 0.5 mg/kg, especially in males. It
is believed that O

- demethylation of the methoxy group and hydroxylation of the triazinyl methyl group are the primary metabolic pathways; while hydroxylation at various sites of the trifluoropropylbenzene moiety is a slower process that increases in imp ortance as the primary pathways approach saturation.

870.7800 Immunotoxicity No study available but requirement waived at this time.

### Page 25 of 32

Appendix B. Review of Human Research

This risk assessment relies in part on data from studies in which adult human sub jects were intentionally exposed to a pesticide or other chemi cal. These data, which include studies from
PHED 1.1 and the AHETF database are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with app licable ethics requirements. For certain studies, the ethics 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 the Agency
website 6



### .

6 http://www.epa.gov/pesticides/science/handler

- exposure

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

- app

- exposure

- data.html

### Page 26 of 32

Appendix C

. Occupati onal Non

- cancer Handler Algorithms

Occupational Non

- cancer Handler Algorithms

Potential daily exposures for occupational handlers are calculated using the following formulas:

where:

E = e xposure (mg ai/day),

UE = u nit e xposure (μg ai/lb ai),

AR = m aximum application rate according to proposed label (lb ai A or lb ai/gal), and

A = a rea treated or amount handled (e.g., A/day, gal/day).

The daily doses are calculated using the following formula:

where:

ADD = average daily dose absorbed in a gi ven scenario (mg ai/kg/day),

E = e xposure (mg ai/day),

AF = absorption fa ctor (dermal and/or inhalation), and

BW = body weight (kg).

Margin of Exposure: Non

- cancer risk estimates for each application handler scenario are calculated using a Margin of E xposure (MOE), which is a ratio of the toxicological endpoint to the daily dose of concern. The daily dermal and inhalation dose received by occupational
handlers a re compared to the appropriate POD ( i.e.

, NOAEL) to assess the risk to occupational
handler s for each exposure route. All MOE values a re calculated using the following formula:

where:

MOE = margin of exposure: value used by HED to represent risk estimates (unitless),
POD = point of departure (mg/kg/day), and

ADD = average daily dose abso rbed in a given scenario (mg ai/kg/day).

### Page 27 of 32

Appendix D

. Dietary Exposure/Risk Modeling Input and Output

DEEM

- FCID Acute Input s File

Filename: C: \ Users \ jlangsda \ Documents \ Chemicals \ SUs \ Prosulfuron \ Dietary

Assessment \ 129031A.R08

Chemical: Prosulfuron
RfD(Chr onic): .053 mg/kg bw/day NOEL(Chronic): 5.3 mg/kg bw/day RfD(Acute): .1 mg/kg bw/day NOEL(Acute): 10 mg/kg bw/day Date created/last modified: 05

- 08

- 2015/15:00:26 Program ver. 3.16, 03

- 08

- d

---------------------------------------------------------- ------------------------- EPA Crop Def Res Adj.Factors Comment Code Grp Commodity Name (ppm) #1 #2

---------- ---- ------------------------------- ---------- ------ --- --- ------- 1500025000 15 Barley, pearled barley 0.010000 1.000 1.000 5F4469 1500025001 15 Barley, pearled barley

- babyfood 0.010000 1.000 1.000 5F4469 1500026000 15 Barley, flour 0.010000 1.000 1.000 5 F4469 1500026001 15 Barley, flour

- babyfood 0.010000 1.000 1.000 5F4469 1500027000 15 Barley, bran 0.010000 1.000 1.000 5F4469

1500065000 15 Buckwheat 0.010000 1.000 1.000 5F4469

1 500066000 15 Buckwheat, flour 0.010000 1.000 1.000 5F4469 1500120000 15 Corn, field, flour 0.010000 1.000 1.000 5F4469 1500120001 15 Corn, field, flour

- babyfood 0.010000 1.000 1.000 5F4469

15001210 00 15 Corn, field, meal 0.010000 1.000 1.000 5F4469 1500121001 15 Corn, field, meal

- babyfood 0.010000 1.000 1.000 5F4469 1500122000 15 Corn, field, bran 0.010000 1.000 1.000 5F4469

1500123000 15 Corn, field, starch 0.010000 1.000 1.000 5F4469 1500123001 15 Corn, field, starch

- babyfood 0.010000 1.000 1.000 5F4469 1500124000 15 Corn, field, syrup 0.010000 1.500 1.000 5F4469 1500124001 15 Corn, field, syrup

- babyfood 0.010000 1.500 1.000 5F4469 1500125000 15 Corn, field, oil 0.010000 1.000 1.000 5F4469 1500125001 15 Corn, field, oil

- babyfood 0.010000 1.000 1.000 5F4469 1500126000 15 Corn, pop 0.010000 1.000 1.000 5F4469 1500127000 15 Corn, sweet 0.010000 1.000 1.000 5F4469 1500127001 15 Corn, sweet

- babyfood 0.010000 1.000 1.000 5F4469 1500226000 15 Millet, grain 0.010000 1.000 1.000 5F4469 1500231000 15 Oat, bran 0.010000 1.000 1.000 5F4469 1500232000 15 Oat, flour 0.010000 1.000 1.000 5F4469 1500232001 15 Oat, flour

- babyfood 0.010000 1.000 1.000 5F4469 1500233000 15 Oat, groats/rolled oats 0.010000 1.000 1.000 5F4469 1500233001 15 Oat, groats/rolled oats

- babyfood 0.010000 1.000 1.000 5F4469 1500328000 15 Rye, grain 0.010000 1.000 1.000 5F4469 1500329000 15 Rye, flour 0.010000 1.000 1.000 5F4469 1500344000 15 Sorghum, grain 0.010000 1.000 1.000 5F4469 1500345000 15 Sorghum, syrup 0.0100 00 1.000 1.000 5F4469 1500381000 15 Triticale, flour 0.010000 1.000 1.000 5F4469 1500381001 15 Triticale, flour

- babyfood 0.010000 1.000 1.000 5F4469 1500401000 15 Wheat, grain 0.010000 1. 000 1.000 5F4469 1500401001 15 Wheat, grain

- babyfood 0.010000 1.000 1.000 5F4469 1500402000 15 Wheat, flour 0.010000 1.000 1.000 5F4469 1500402001 15 Wheat, flour

- babyfood 0.010000 1.000 1. 000 5F4469 1500403000 15 Wheat, germ 0.010000 1.000 1.000 5F4469 1500404000 15 Wheat, bran 0.010000 1.000 1.000 5F4469

1500405000 15 Wild rice 0.010000 1.000 1.000

8 601000000 86A Water, direct, all sources 0.015000 1.000 1.000 8602000000 86B Water, indirect, all sources 0.015000 1.000 1.000



### DEEM

- FCID Acute Results File

US EPA Ver. 3.18 , 03

- 08

- d

DEEM

- FCID ACUTE Analysis for PROSULFURON NHANES 2003

- 2008 2

- Day Residue file: 129031A.R08 Adjustment factor #2 used. Analysis Date: 05

- 08

- 2015/15:02:46 Residue file dated: 05

- 08

- 2015/15:00:26

### Page 28 of 32

NOEL (A cute) = 10.000000 mg/kg body

- wt/day RAC/FF intake summed over 24 hours

Run Comment: ""

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

Summary calculations

-- per capita:

--- 95th Percentile

---- --- 99th Percentile

--- - --- 99.9th Percentile

---- Exposure % aRfD MOE Exposure % aRfD MOE Exposure % aRfD MOE

---------- ------- -------- ---------- ------- -------- ---------- ------- -------- Total US Population:

0.000866 0.87 11551 0.0014 25 1.43 7017 0.002646 2.65 3779

All Infants:

0.002641 2.64 3786 0.003503 3.50 2854 0.005117 5.12 1954

Children 1

- 2:

0.001389 1.39 7197 0.002172 2.17 4604 0.004799 4.80 2083

Children 3

- 5:

0.001132 1.13 8835 0.001675 1.68 5970 0.002625 2.62 3809

Children 6

- 12:

0.000863 0.86 11587 0.001358 1.36 7366 0.002169 2.17 4609

Youth 13

- 19:

0.000729 0.73 13721 0.001172 1.17 8534 0.001727 1.73 5789

Adults 20

- 49:

0.000838 0.84 11939 0.001222 1.22 8185 0.001770 1.77 5648

Adults 50

- 99:

0.000742 0.74 13485 0.001127 1.13 8872 0.001714 1.71 5833

Female 13

- 49:

0.000853 0.85 11724 0.001223 1.22 8178 0.001721 1.72 5810



### DEEM

- FCID Chronic Input s File

Filename: C: \ Users \ jlangsda \ Documents \ Chemicals \ SUs \ Prosulfuron \ Dietary

Assessment \ 129031C.R08

Chemical: Prosulfuron RfD(Chronic): .053 mg/kg bw/day NOE L(Chronic): 5.3 mg/kg bw/day RfD(Acute): .1 mg/kg bw/day NOEL(Acute): 10 mg/kg bw/day Date created/last modified: 05

- 07

- 2015/16:21:26 Program ver. 3.16, 03

- 08

- d

----------------------------------------------------------------------------------- EPA Crop Def Res Adj.Factors Comment Code Grp Commodity Name (ppm) #1 #2

---------- ---- ------------------------------- ---------- ------ ------ ------- 1500025000 15 Barley, pearled barley 0.010000 1.000 1.000 5F4469 1500025001 15 Barley, pearled barley

- babyfood 0.010000 1.000 1.000 5F4469 1500026000 15 Barley, flour 0.010000 1.000 1.000 5F4469 1500026001 15 Barley, flour

- babyfood 0.010000 1.000 1.000 5F4469 1500027000 15 Barley, bran 0.010000 1.000 1.000 5F4469

1500065000 15 Buckwheat 0.010000 1.000 1.000 5F4469 1500066000 15 Buckwheat, flo ur 0.010000 1.000 1.000 5F4469 1500120000 15 Corn, field, flour 0.010000 1.000 1.000 5F4469 1500120001 15 Corn, field, flour

- babyfood 0.010000 1.000 1.000 5F4469 1500121000 15 Corn, field, meal 0.010000 1.000 1.000 5F4469 1500121001 15 Corn, field, meal

- babyfood 0.010000 1.000 1.000 5F4469 1500122000 15 Corn, field, bran 0.010000 1.000 1.000 5F4469 1500123000 15 Corn, field, starch 0.010000 1.000 1.000 5F4469 1500123001 15 Corn, field, starch

- babyfood 0.010000 1.000 1.000 5F4469 1500124000 15 Corn, field, syrup 0.010000 1.500 1.000 5F4469 1500124001 15 Corn, field, syrup

- babyfood 0.010000 1.500 1.000 5F4469 1500125000 15 Corn, field, oil 0.010000 1.000 1.000 5F4469 1500125001 15 Corn, field, oil

- babyfood 0.010000 1.000 1.000 5F4469 1500126000 15 Corn, pop 0.01000 0 1.000 1.000 5F4469 1500127000 15 Corn, sweet 0.010000 1.000 1.000 5F4469 1500127001 15 Corn, sweet

- babyfood 0.010000 1.000 1.000 5F4469 1500226000 15 Millet, grain 0.010000 1.0 00 1.000 5F4469 1500231000 15 Oat, bran 0.010000 1.000 1.000 5F4469 1500232000 15 Oat, flour 0.010000 1.000 1.000 5F4469 1500232001 15 Oat, flour

- babyfood 0.010000 1.000 1.0 00 5F4469 1500233000 15 Oat, groats/rolled oats 0.010000 1.000 1.000 5F4469

### Page 29 of 32

1500233001 15 Oat, groats/rolled oats

- babyfood 0.010000 1.000 1.000 5F4469 1500328000 15 Rye, grain 0.010000 1.000 1.000 5F4 469 1500329000 15 Rye, flour 0.010000 1.000 1.000 5F4469 1500344000 15 Sorghum, grain 0.010000 1.000 1.000 5F4469 1500345000 15 Sorghum, syrup 0.010000 1.000 1.000 5F4469

150 0381000 15 Triticale, flour 0.010000 1.000 1.000 5F4469 1500381001 15 Triticale, flour

- babyfood 0.010000 1.000 1.000 5F4469 1500401000 15 Wheat, grain 0.010000 1.000 1.000 5F4469

1500401001 15 Wheat, grain

- babyfood 0.010000 1.000 1.000 5F4469 1500402000 15 Wheat, flour 0.010000 1.000 1.000 5F4469 1500402001 15 Wheat, flour

- babyfood 0.010000 1.000 1.000 5F4469

1500403000 15 W heat, germ 0.010000 1.000 1.000 5F4469 1500404000 15 Wheat, bran 0.010000 1.000 1.000 5F4469

1500405000 15 Wild rice 0.010000 1.000 1.000 8601000000 86A Water, direct, all sources 0.013000 1.000 1.000 8602000000 86B Water, indirect, all sources 0.013000 1.000 1.000



### DEEM

- FCID Chronic Results File

US EPA Ver. 3.16, 03

- 08

- d

DEEM

- FCID Chro nic analysis for PROSULFURON NHANES 2003

- 2008 2

- day

Residue file name: C: \ Users \ jlangsda \ Documents \ Chemicals \ SUs \ Prosulfuron \ Dietary

Assessment \ 129031C.R08 Adjustment factor #2 used.

Anal ysis Date 05

- 08

- 2015/14:36:23 Residue file dated: 05

- 07

- 2015/16:21:26 Reference dose (RfD, Chronic) = .053 mg/kg bw/day

=============================================================================== Total exposure by population sub group

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

Total Exposure

----------------------------------- Population mg/kg Percent of Subgroup body wt/day Rfd

-------------------------------------- ------------- ---------------- Total US Population 0.000 311 0.6% Hispanic 0.000303 0.6%

Non

- Hisp

- White 0.000318 0.6%

Non

- Hisp

- Black 0.000264 0.5%

Non

- Hisp

- Other 0.000350 0.7% Nursing Infants 0.000272 0.5%

Non

- Nursing Infants 0.000973 1.8%

Female 13+ PREG 0.000289 0.5%

Children 1

- 6 0.000439 0.8%

Children 7

- 12 0.000291 0.5%

Male 13

- 19 0.000236 0.4%

Fem ale 13

- 19/NP 0.000248 0.5%

Male 20+ 0.000287 0.5% Female 20+/NP 0.000312 0.6%

Seniors 55+ 0.000286 0.5%
All Infants 0.000756 1.4%

Female 13

- 50 0.000302 0.6%
Children 1

- 2 0.000483 0. 9%

Children 3

- 5 0.000422 0.8%
Children 6

- 12 0.000306 0.6%
Youth 13

- 19 0.000242 0.5%

Adults 20

- 49 0.000305 0.6%
Adults 50

- 99 0.000292 0.6%
Female 13

- 49 0.000302 0.6%

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

### Page 30 of 32

Appendix E. Nomenclature and Physical/Chemical Properties

Table E1 . Prosulfuron Nomenclature. Compound

Common name Prosulfuron

IUPAC name 1

- (4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)

- 3

- [2

- (3,3,3

- trifluoropropyl)

- phenylsulfonyl]

- urea CAS name N

- [[(4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)amino]carbonyl]

- 2

- (3,3,3

- trifluoropropyl)benzenesulfonamide CAS registry number 94125

- 34

- 5

Table E2 . Physicochemical Properties of the Technical Grade Prosulfuron

Parameter Value Reference

Meltin g point/range 155°C MSDS pH Not Applicable Bulk density (g ml

- 1 )/Specific gravity 1.45 Water solubility (g/L) at 25 oC 4.0 at pH 6.8 Solvent solubility (g/L) at room
temperature Acetone: 160 (purity: 95.1 %)

Toluene : 6.1

Dichloromethane : 180 Ethyl acetate : 56

n

- Hexane : 0.006

Ethanol : 8.4

n

- octanol :1.4 Vapor pressure < 3.5x10

- 6 Pa at 25 °C Dissociation constant, pK
a pKa = 3.76 Octanol/water partition coefficient (log Pow) pH5 : 1.5 at 25°C

UV/visible absorption L mol

- 1 cm - 1 ε = 21645 l x mol

- 1 x cm - 1 at λ max = 227.5 nm
shoulder at 250 nm No absorption >290 nm

### Page 31 of 32

Appendix F. Spray Drift Detailed Description

Off

- target movement of pesticides can occur via many types of pathways and it is governed by a variety of facto rs. 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 contact with residues can eventually lead to exposures (e.g

. , ch ildren playing on lawns where residues have deposited next to treated fields). The potential risk estimates from these residues can be calculated using drift modeling coupled with methods employed for residential risk assessments for turf products.

The a pproach to be used for quantitatively incorporating spray drift into risk assessment include assessing 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 result ing in an exposure scenario. Aside from the predicted residues available for transfer, the routes of exposure and assessment methodology is analogous to how exposures to turf products are considered in risk assessment.

In order to evaluate the drift po tential 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 t o address drift from the agricultural applications of flufenpyr

- ethyl. In the spray drift scenario, the deposited residue value was determined based on the amount of spray drift that may occur at varying distances from the edge of the treated field using the AgDrift ® 

### (v2.1.1) model. Exposures were considered for 50 feet wide lawns where the nearest side of the property was directly adjoining the treated field (at field edge) and at varied distances up to 300 feet downwind of a treated field. Once the dep osited residue values were determined, the remainder of the spray drift assessment was based on the algorithms and input values specified in the recently revised (2012) Standard Operating Procedures For Residential Risk Assessment (SOPs)

.

A screening a pproach was developed for situations where specific label guidance for application parameters is not available. 7

, 8 

### AgDrift ® 

### is appropriate for use only when applications are made by aircraft, airblast 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. In all cases, each scenario is to be evaluated unless it is not plausible based on the anticipated use pattern (e.g., herbicides are n ot 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. These drift estimates represent plausible options based on the ava ilable pesticide
labels.

7 http://www.agdrift.com/

8 Note that for many cases the scenarios outlined in the screening approach represent actual use practice so risk assessors sho uld
be aware and characterize these appropriately.

### Page 32 of 32

Appendix G

. Submittal of Analytical Reference Standards (860.1650)

A nalytical reference standard s for prosulfuron are current ly available in EPA’s National Pesticide Standards Repository ( NPSR ) and have an expiration date of 0 2 /28/2019 ( email communication between G. Verdin and J. Van Alstine, 0 5/ 0 7/2015 )

. T he registrant is required to
maintain reasonable amount s of the reference standard s for prosulfuron in the NPSR as long as tolerances remain published in 40 CFR §180. 481

. W hen necessary, new reference standard s, or updated certificates of analysis ( COA s), should be sent to the Analytical Chemistry Branch ( ACB ) , which is located at Fort Meade, MD. It should be sent to the attention of either Theresa Cole or Thuy Nguyen at th e address listed below, along with a letter of transmittal. Please note
that the full 9

- digit Z IP Code is required , or the mail will be returned to the registrant.

USEPA National Pesticide Standards Repository Analytical Chemistry Branch/BEAD/OPP 701 Mapes Road Fort George G. Meade, MD 20755

- 5350

The letter of transmittal should include the assay of the standard, name of the analytical method used, a statement of principal impurities, purification procedures employed, storage requirements, a nd special precautions for safe handling. Replacement of standards , or updated COAs, may be required periodically if supplies are exhausted, if the standards expire, or if decomposition occurs during storage. Material Safety Data Sheets (MSDSs) must acco mpany all analytical standards as specified by the Occupational Safety and Health Administration (OSHA)
in 29CFR §1910.1200.