### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

MEMORANDUM

DA TE: Septe mber 14

, 20 1 5 

### WASH IN GTON, D .C. 20460

OFFICE OF
CHEMICAL SAFETY AND
POLLUTION PREVENTION



### SUBJECT: Rimsulfuron

. Human H ea lth Draft Risk A ssess ment fo r Regi s tration R eview.



### PC Co de: 1 29009



### Deci s ion No.: 500059



### Petition No

. : NA 

### DP Barcode: D42 5 70 3 

### Regi s tration No.: NA 

### Regulatory Action: Regi s tration R ev ie w


### Case No.: 72 

### I 8 Risk Assessment Type: Single Chemical Agg reg a te



### TXR No.: 

### NA CAS No

. : 1 2293 1- 48 -0

40 CFR: 

### § 180.478 

### MRID No

. : NA

FROM:



### THROUGH:

TO: M in erva**rcado-Felician~**

## 1 / oxic I 

## t**~** Kri s tin Rur y, Biolo g i s t 

## (!f,1/**'-t;:.~ -.:::** **<t---** Meherct Neg u ss i e, Chemis t 

## /Ye.A 

## erd**~(f** ll.J'<f<_ t:. Risk A ss e ss m e nt Bran c h III

Health Effects Division (7509 P )

C hri s tin e O lin ge r ,

# hi**e~ J**  /_

# ~~ Risk Assessment Bran c h /

## ~ /--

Health Effects Divi s i o 9 P )

Jose Gayoso

, C hemic a l R ev i ew Manager

Cat hr y n Britton

, Ri sk Mana ger
Risk Mana ge m e nt a nd Im p l emen t a ti o n Branch II

Pes ti cide R e -R eg i s tration Divi s i o n (7508 P )

This draft ri sk assessment ( DRA ) eva luat es th e existing u s e s of rim su lfuron as part of R egistrat ion

Review

. Rimsulfuron i s a s ul fo n y lur ea (SU) h e rbicid e

. T h e Agency i s reviewing a ll o f th e SU

h e rbicides joint l y under R eg istr at i o n Review

. For rim s ul f uro n , s ignificant c han ges re l ative to th e
last risk assessment (C

. Walls, 04 0 872 2, 0 7 / 02 / 2014) in clude a new in c id enta l ora l point of departure ( POD ) se l ected t o assess sp r ay d ri ft ex p os ur e / ri sk es timat es, and re- ev aluation of th e de rm a l POD. A ll other POD s r e m ai n the same s i nce the l ast risk assessment. So m e studies u sed

fo r e ndp o in t se l ec tion h ave conse r vat i ve No Observed Adve r se E ff ec t L evel / L owes t Observed

Adverse Effec t Leve l (N OAE L/ LOA E L) va lu es that hav e n ot b ee n upd a ted to r eflec t c urr e nt

sta ndard s for evalua tin g toxicity studies. U pdate s wo uld r esu l t in hi ghe r NOAEL/LOAEL value s and, g i ven the cu tT en t ri sk picture

, would n o t imp ac t the ove r all findings of th e ri sk assess m e nt.

### Rimsulfuron Human He a lth Ri s k Assessment DP No. D4 25703



### Tab l e of Contents

1. 0 Executive Sun1 1nar y

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

2

. 0 I- I E D Recom m e ndation s

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

2. 1 To l e r ance Cons id e ration s

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

2.2 D ata D efic i e ncies

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

3.0 Intr oduct ion

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

3. 1 Use Profile & 

### A nticipated Exposure P athways

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

3 .2 Considera ti o n of E nvironm e nt al Ju stice

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

4.0 1-i azard Cha r acte ri za tion

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

4.1 Summary of Toxicolog i ca l Effects

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

4

. 2 Safety Factor for In fa nt s and Child r en (FQ P A Safety Factor)

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

4

. 3 Toxicity Endpo int and Point of D epart ur e Selections

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

4.4 Endocr in e Disruption

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

5.0 Diet ary Ri s k Assessment

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

5 .1 Residu e Chen1istry

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

5 .2 Water Res idu e Pr ofile

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

5.3 Di etary (Food + Water) Exposu r e Assessment..

... .. .. ................................... . ................. 13

6.0 Residential (Non-Occ u pa ti onal) Expos ur e / Ri s k C h a r acter i za tion

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

6 .1 Spray Drift

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

6. 1

. l Incid enta l Oral Risk Estimates From L awn D epos iti o n Adjacent to App li cations 15

6.2 Residential Bystand e r Post-Application In halation Exposu r e

.......... . ......... . ...................... 1 6

7.0 Aggregate Exposure / Ri sk C h aracterizatio n

....................... .. ............. . ...... . .. ... ... .. .. . ............ 1 7

8.0 Occupational Exposure / Ri s k C hara c t e ri zat i o n

................................................ . .............. ... 1 7

8.1 Occupational Handler

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

8.1. I Occupational H a ndl er Expos ur e , Assu mpt io n s and Ri sk Es timate Equations

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

8. 1 .2 Sun unary of Occupat i o nal Handler Non

- Cance r E xpos ur e and Risk Es timate

......... 18

8

. 2 Occupational P os t- Ap pl ication Expo su re

...................................................................... 21

8.2. l Occupational Inhalation Post-Application Exposure

.......... ......... ................. ............. 21

8.2.2 Occ up a ti ona l P os t -a ppli cat ion Dermal Exposu r e D ata a nd Assumptions

........... ....... 21

8.2.3 Re s tricted E ntr y In terva l

............. ... .................. .. .............. .. . .. . ... . .. ........ ... . ..... .. . ........ ... 22

9.0 Cumulative Exposure / Risk Characterization

........... .. ... . ......... . .............. . ........................... 23

I 0.0 Public H ea lth and Pe s ticid e Epidemiology Data

..... . .... .... .......... ......... ............ .................. 23

P age 2of36

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 3 of 36 11.0 References

................................ ................................ ................................ .......................... 24

Appendix A. Toxicology Profile

................................ ................................ ................................ . 25

A.1 Toxicology Data Requirements

................................ ................................ ...................... 25

A.2 Toxicity Profiles

................................ ................................ ................................ ............. 26

Append ix B. Physical/Chemical Properties of Rimsulfuron and Metabolites

.............................. 29

Appendix C. Review of Human Research

................................ ................................ ................... 31

Appendix D. International Harmonization

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

Appendix E. DFR and TTR Data Waiver Rationale

................................ ................................ ... 33

Appendix F. Sulfonylurea Pesticide Class Dermal Toxicity Data

................................ ............... 34

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 4 of 36 1.0 Executive Summary

Rim sulfuron ( 1

- [4,6

- dimethoxypyrimidin

- 2

- yl]

- 3

- [ 3

- ethylsulfonyl

- 2

- pyridylsulfonyl] urea ) is a systemic herbicide belonging to the sulfonylurea group of herbicides

. It is currently regis tered to E. I. du Pont de Nemours and Co. (DuPont) for use on bushberries, caneberries, chicory, field

corn , grapes, potatoes, soybeans, tomatoes, various tree fruits, and t ree nuts for pre

- and post

emergence control of annual grasses, broadleaf weeds, and yellow nutsedge. Permanent rimsulfuron tolerances are currently established in 40 CFR §180.478. Since the last risk

assessment ( C

. Walls , D4087 22, 07/02 /2014 ) and the scoping document ( C. Walls , D 401381

, 05/2 1/ 2012 )

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

. A new incidental oral point of departure (POD) was selected, and the dermal POD was re

- evaluated. All
other PODs remain the same s ince last risk assessment. It is important to note that if all
NOAELs/LOAELs were re

- evaluated according to current toxicological policies, they would be higher; therefore, this risk assessment is considered extremely conservative. E xisting uses have
bee n reevaluated here using updated occupational and dietary exposure assessment methodologies. A spray drift assessment was also conducted to evaluate exposure resulting from drift from agricultural applications to surrounding residential areas. There are no risk estimate s of concern for the existing uses of rim sulfuron

.

2.0 HED Recommendations

The existing US tolerance s for pistachio (0.01 ppm) need s to be removed from 40 CFR §180.4 7 8(a)

, since this commodit y is included in crop group Nut, tree, group 14

- 12 (0.01 ppm).

The existing tolerances for citrus fruits, pome fruits, stone fruits, and tree nuts need to be revised

to Fruit, citrus, group 10

- 10

, Fruit, pome, group 11

- 10

, Fruit, stone, group 12

- 12 , and Nut, tree, group 14

- 12 . The proposed tolerance chang es are a result of revisions in the crop groups and are conversions from existing groups/subgroups. The revisions are presented in Table 2. 1.

2.1 Tolerance Considerations

Tolerances for residues of rimsulfuron [N

- ((4,6

- dimethoxypyrimidin

- 2

- yl)aminocarbonyl)

- 3

- (ethylsulfonyl)

- 2

- pyridinesulfonamide] are listed in 40 CFR § 180.478 and are expressed in terms of rimsulfuron only. Permanent tolerances are established for residues of rimsulfuron at levels ranging from 0.01 ppm in/on various tree fruits, tree nuts and grapes to 0.1 ppm in/on potatoes and field corn commodities [40 CFR §180.478(a )]. Tolerances are recommended for sorghum (grain, forage and stover) at 0.01 ppm each. The tolerance expression under 40 CFR §180.478(a) is correct and reflects measurement a nd compliance of rimsulfuron residues. Compliance with the tolerance levels is to be determined by measuring only rimsulfuron.

At this time, there are no Codex maximum residue limits (MRLs) established for residues of
rimsulfuron. The US tolerances for b ushberry subgroup 13

- 07B (0.01 ppm), field corn grain, potatoes, and tomatoes are harmonized with Canada. Canada has established an MRL at 0.05 ppm on lowbush blueberries. There is a disharmony on livestock feedstuffs because Canada
does not establish MR Ls on feedstuffs. Refer to Appendix D

.

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 5 of 36 Table 2.1. Tolerance Recommendations for Rimsulfuron

Commodity Established

Tolerance (ppm) Recommended

Tolerance (ppm) Comments

Fruit, citrus, group 10 0.01 0.01 Fruit, citrus, group 10

- 10
Fruit, pome, group 11 0.01 0.01 Fruit, pome, group 11

- 10
Fruit, stone, group 12 0.01 0.01 Fruit, stone, group 12

- 12
Nut, tree, group 14 0.01 0.01 Nut, tree, group 14

- 12

Pistachio 0.01 None Remove Nut, tree, group 14

- 12 (0.01 ppm)
Bushberry, subgroup 13

- 07B 0.01 0.01 Bushberry subgroup 13

- 07B
Caneberry, subgroup 13

- 07A 0.01 0.01 Caneberry subgroup 13

- 07A
Grain, aspirated fractions 4.5 4.5 Grain, aspirated grain fractions
Corn, field, forage 0.4 0.40
Corn, field, grain 0.1 0.10

Potato 0.1 0.10



### 2.2 Data Deficiencies

There are no data deficiencies for rimsulfuron.

3.0 Introduction

3.1 Use Profile & Anticipated Exposure Pathways

Rimsulfuron is formulated as dry flowable (DF) and liquid formulations. Currently registered
labels include three technical/manufacturing use product label s , and 38 end use product l abels. In general, rimsulfuron may be applied once or twice per year or growing season . Registered agricultural use sites include the following: acetolactate synthase (ALS) herbici de tolerant sorghum; blackberries ; citrus fruit; field corn; field grown tomatoes and tomatoes for transplant;

grapes; glyphosate resistant soybeans and corn; highbush and lowbush blueberries; pre

- plant cotton, peanuts, and soybeans; pome fruit; potatoes a nd potatoes grown for seed; raspberries; stone fruit; sulfonylurea herbicide tolerant chicory; and tree nuts. Registered non

- agricultural use sites include sod farms, non

- residential turf (including professional and college sports fields, commercial turf) , golf courses, roadsides, industrial sites, utility substations, rangeland, and other

non

- crop sites. Rimsulfuron may be applied using groundboom

, aerial , chemigation, and
handheld application equipment. All the registered rimsulfuron labels require occ upational handlers to wear long

- sleeved shirts, long pants, shoes, and socks. All but two of the registered labels (EPA Reg. No s . 67760

- 125 and 83100

- 42) require the addition of chemical resistant gloves. Some labels require the addition of a respirator, or protective eyewear. The restricted entry intervals (REIs) range from 4 hours to 24 hours on the registered rimsulfuron labels. Those products with additional PPE other than gloves, and REIs greater than 12 hours are all co

formulated products with ni cosulfuron, atrazine, dicamba, or isoxaflutole.

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 6 of 36 Individuals may be exposed to rimsulfuron via their diet (food and drinking water). There are no registered uses for rimsulfuron that will result in direct non

- dietary (i.e., residential) post

application exposures. Additionally, there is the potential for indirect exposure (incidental oral and dermal) to rimsulfuron related to spray drift. Agricultural /occupational workers may be exposed (dermal and inhalation) to rimsulfuron during mixing, loading, and/ or applying the herbicide as well as during post

- application activities. Exposure to rimsulfuron 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 d urations, the handler and post

- application assessment is protective of both durations. Exposure to rimsulfuron via spray drift is expected to
be short

- term only.

Table 3.1 . Summary of Directions for Use of Rimsulfuron.

Applic. Timing, Type, and Equip. Formulation Max. Applic. Rate (lb ai/A) Max. Seasonal Applic. Rate (lb ai/A)

Field Corn

Groundboom, Aerial, Chemigation DF 0.031 0.062
Liquid 0.0079 0.063
Non Crop Sites 1

Groundboom, Aerial, Handheld DF 0.063 0.063
Sod Farms, Seed Farms, Golf Courses, Professionally Managed Sports Fields, Industrial and Commercial Lawns, and Other Similar Non

- Residential Areas
Groundboom, Handheld DF 0.016 0.063

Potatoes and Potatoes Grown for Seed
Ground, Aerial, Chemigation DF 0.023 0.039

Field Grown Tomatoes and Tomato Transplants

Ground and Handheld DF 0.063 0.063

Pome Fruit, Citrus Fruit, Tree Nuts, Stone Fruit, Grapes
Ground, Chemigation, Handheld DF 0.063 0.063

Pre

- Plant Cotton and Soybeans
Ground, Aerial, Chemigation DF 0.021 0.31

Pre

- Plant Peanuts
Ground, Aerial, Chemigation DF 0.016 0.31

Blueberry (Highbush and Lowbush) and Bushberry Subgroup 13

- 07B
Ground, Chemigation, Handheld DF 0.063 0.063

Caneberry (Raspberry and Blackberry) and Caneberry Subgroup 13

- 07A

Ground, Chemigation, Handheld DF 0.063 0.063
Chicory
Ground only DF 0.063 0.063
ALS Tolerant Sorghum

Ground, Aerial DF 0.016 0.50

Non

- Residential Turfgrass

Ground, Aerial DF 0.031 0.031

1 . Non

- Crop use sites include: airports, highway, railroad, and utility rights of way; sewage disposal areas, uncultivated agricultural areas; non

- crop producing areas.

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 7 of 36 3.2 Consideration of Environmental Justice

Potential areas of environmental justice conce rns, to the extent possible, were considered in the preliminary human health risk assessment for rim sulfuron , in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and

Low

- Income Population s," 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

- established procedures. In line with OPP policy, HED estimat es 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 consumpti on 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 cate gorized by subgroups based on age and ethnic group. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, non

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

- application are evaluated. Further considerations are currently in development as O PP has committed resources and expertise to the development of specialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.

4.0 Hazard Characterization

T he toxicology database for rimsulfuron is complete. The data requirements for a dermal toxicity study and a subchronic inhalation toxicity study are waived ( J. Van Alstine, TXR 0050008, 4/26/2012; K. Rury, TXR 0056438, 9/17/2012). The latest risk assessm ent was conducted in 2014 ( C. Walls, D408722, 7/2/2014). No new toxicity and/or metabolism data have been received and the endpoints selected for the previous risk assessment remain the same except for the dermal and incidental oral scenarios . A summary of the acute, subchronic, and chronic toxicity profile is presented in Appendix A.

4.1 Summary of Toxicological Effects

Rimsulfuron inhibits the plant enzyme acetolactate synthase (ALS)/acetohydroxy acid synthase (AHAS), leading to the disruption of cell divis ion and elongation in the plant. ALS is not found
in humans or other mammals. A gene coding for a similar protein has been found in humans; however, the protein or function associated with this gene is not known. Currently, the
herbicidal mode of action of rimsulfuron is not relevant to mammals.

After oral administration to rats, rimsulfuron is absorbed into the blood stream, mostly without metabolic changes before excretion. More than 90% of the dose was excreted within 72 hours, mostly as parent comp ound (47

- 71% of excreted compound). Urinary elimination accounted for about 64% of the dose and fecal elimination for about 30%. Low levels were found in the liver, heart, lung, kidney, and muscle 72 hours after a single dose. In addition to those organs , the

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 8 of 36 spleen also had low levels of rimsulfuron after repeated doses. There were no major differences in absorption, distribution, metabolism or excretion between the sexes, except males showed
more distribution to the liver than females.

Dermal absorpt ion studies are not available for rimsulfuron ; however

, an estimated maximum dermal absorption factor (DAF) of 20% is used in this risk assessment, based on the range of DAFs available from dermal penetration studies for other sulfonylureas (9.1

- 17.7%; see Appendix F ).

With repeated oral dosing, rimsulfuron produced very low toxicity in rats, mice, rabbits, and dogs. In most rat and mouse oral toxicity studies, the only effect seen at and above the limit dose (1000 mg/kg/day) was reduced body weight gain

– which is not considered adverse in the absence of absolute body weight changes. In the dog, increased urinary volume and decreased osmolality occurred at 90 days, and kidney, liver and epididymis effects were observed at 52 days. Male sex organ effects (microscopic changes in the testicular artery and tunica albuginea) were also observed in mice; but, only in a long

- term study and only at doses above the limit dose. In a developmental toxicity study in rats, no maternal or fetal effects were found at do ses above the limit dose. In a rabbit developmental study, no developmental effects were observed at doses that showed maternal death. A reproduction study in rats showed decreased body weight in adults and in female pups of the second generation on post natal days (PND) 4 and 7 (but not on PND 0 or 21), in animals dosed at or near the limit dose. Therefore, there is no evidence of increased qualitative or quantitative susceptibility in the young.

No increase in tumor incidence was seen in rats or mice, a nd rimsulfuron was not genotoxic, therefore it is not likely to be carcinogenic. There was no evidence of neurotoxicity or
immuno toxicity in the database. The acute toxicity data indicate that rimsulfuron had low acute oral, dermal, and inhalation toxicit y. Rimsulfuron was not found to be a skin irritant, but was a moderate eye irritant. Rimsulfuron was not a dermal sensitizer.

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

The toxicity database of rimsulfuron is complete and adequate to ass ess susceptibility in the young. There is no evidence of increased qualitative or quantitative susceptibility in the young, there is no evidence of neurotoxicity and exposure estimates are unlikely to underestimate risk; therefore, the FQPA Safety Factor ( 10X) is reduced to 1X.

4.3 Toxicity Endpoint and Point of Departure Selections

For rimsulfuron, a new incidental oral POD was selected, and t he dermal POD was re

- evaluated

. All other PODs remain the same since last risk assessment ( C. Walls, D408722, 07/02/2014 )

. There has been no change to the prior cancer classification. S tudies used for endpoint selection have conservative NOAEL/LOAEL values that have not been updated to reflect current standards for evaluating toxicity studies. Updates would resu lt in higher NOAEL/LOAEL values and, given the current risk picture, would not impact the overall findings of the risk

assessment.

Incidental Oral Endpoint (Short

- and Intermediate

- Term) for Spray Drift Exposure Scenarios : A
90

- day dog toxicity study was u sed to select the dose and endpoint for these scenario s . The

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 9 of 36 LOAEL of 125 mg/kg/day was based on increased urinary volume and kidney weights, and decreased osmolality. The NOAEL was 6. 25 mg/kg/day. The 90

- day dog study is appropriate
for short

- and inter mediate

- term exposure scenarios, and the endpoint is protective of decreased body weight observed in the reproductive study in F2 female pups on PND 7 and PND 14 at 1316 mg/kg/day. The RAB3 risk assessment team recognizes that the incidental oral POD (6.2 5 mg/kg/day) is similar to the chronic dietary POD (11.8 mg/kg/day). Th e incidental oral toxicity endpoint and NOAEL are considered conservative. I f the study (90

- d ay dog toxicity study ) w as

re

- evaluated according to current toxicological practices, the study NOAEL/LOAEL would be higher. However such change in NOAEL ( POD ) would lead to larger MOEs than those currently calculated and therefore would not impact the findings of this risk assessment. Application of a 100

- fold uncertainty factor (10X intersp ecies and 10X intraspecies) has been determined to be appropriate for the incidental oral exposure scenario s . The FQPA Safety Factor
has been reduced to 1X as explained in section 4 .3 above.

Dermal Endpoints for Occupational and Non

- Occupational Expos ure Scenarios : A dermal endpoint was not selected for risk assessment

. There is no 28

- day dermal toxicity study
available on rimsulfuron ; however, the HED Hazard and Science Policy Council (HASPOC)
recommended that the dermal toxicity study requirement be waived, b ased on a Weight of
Evidence (WoE) approach ( J. Van Alstine, TXR 0050008, 4/26/2012). A dermal risk assessment is not warranted because rimsulfuron is not expected to be toxic through the dermal route since :

(1) R imsul furon has low acute dermal toxicity (Category III)

, suggesting that the chemical either has low toxicity (in general) via the dermal route and/or is not absorbed via the dermal route in enough quantity to produce a systemic effect

(2) T here is no quantitative offspring susceptibility in the toxicity database

, therefore there is no concern for toxic effects on the young different from those on adults, via the dermal or any other routes of exposure,

(3) M ost sulfonylureas for which guideline dermal studies were subm itted to the Agency showed no effects through the dermal route up to the limit dose ( 13 out of 15 studies; see Table F.2 in Appendix A); in fact the requirement for a guideline dermal toxicity study was waived for 7 sulfonylureas (including rimsulfuron) b ased on a weight of evidence
that included consideration of the low dermal toxicity and low dermal penetration of the sulfonylurea class of pesticides (see Table F.3 in Appendix F) and

(4) D ermal absorption is generally low (DAF < 20%) for sulfonylureas (see table F1 in appendix F)

.

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 10 of 36 Table 4.3.1. Summary of Toxicity Endpoints and Points of Departure for Rimsulfuron for Use in
Human Risk Assessment.

Exposure
Scenario Point of

Departure Uncertainty/

FQPA Safety

Factors RfD, PAD, Level

of Concern for
Risk Assessment Study and Toxicological
Effects

Acute Dietary: All populations An endpoint attributable to a single dose was not identified in the database.

Chronic Dietary: All populations NOAEL= 11.8

mg/kg/day UF A = 10

UF H = 10

FQPA SF =

1X Chronic RfD =

0.118 mg/kg/day

cPAD = 0.118 mg/kg/day Combined Chronic/

Carcinogenicity

– Rat
LOAEL = 121 mg/kg/day based on decreased body weight gains and liver effects.

Incidental Oral:
Short

- and
Intermediate

- Term NOAEL= 6. 25

mg/kg /day UF A = 10

UF H = 10

FQPA SF =

1X Residential LOC

for MOE = 100 90

- day toxicity study

– Dog

LOAEL = 125 mg/kg/day based on increased urinary volume, kidney weights, and decreased osmolality.

Inhalation Exposure:
Short

- and
Intermediate

- Term NOAEL= 6. 25

mg/kg /day

Inhalation toxicity assumed to be equivalent
to oral. UF A = 10

UF H = 10 Occupational

LOC for MOE =
100 90

- day toxicity study

– Dog

LOAEL = 125 mg/kg/day
based on increased urinary volume, kidney weights, and decreased osmolality

.

Dermal Exposure:
Short

- and
Intermediate

- Term A dermal endpoint was not selected because rimsulfuron is not expected to be toxic

through the dermal route

.

Cancer (oral, dermal, inhalation) Not a carcinogen based on the lack of evidence of carcinogenicity in the rats and mice.

UF = uncertainty factor, FQPA SF = FQPA safety factor, 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 ex posure, LOC = level of concern, FQPA = Food Quality Protection Act.



### 4.4 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 ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, dev elopmental and reproductive effects in different taxonomic groups. As part of its most recent registration decision for rimsulfuron , EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment
scenarios from the existin g hazard database. However, as required by FFDCA section 408(p), rimsulfuron is subject to the endocrine screening part of the Endocrine Disruptor Screening

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 11 of 36 Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pe sticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

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

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

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

Under FFDCA section 408(p), the Agency must screen all pesticide chemical s. 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
che micals identified for EDSP screening was publi shed on June 14, 2013 1 

### 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 lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website. 2



### 5.0 Dietary Risk Assessment

The residue chemistry data and environmental fate data are adequate to assess human exposure. The dietary exposure assessments are considered conservative and based on reliable data and will not underestimate exposure/risk. An unrefined chronic dietary a ssessment was conducted using tolerance level residues, default processing factors, and assuming 100% of the crops were treated for the registered crop uses.

5.1 Residue Chemistry

The nature of the residue of rimsulfuron in plants and livestock has been adeq uately delineated based on metabolism studies conducted with rimsulfuron in field corn, potatoes, tomatoes, lactating goats, and laying hens. The metabolic pathways were found to be similar in plants and livestock. The major route of rimsulfuron metaboli sm/degradation involves sulfonylurea bridge contraction, with sulfonylurea bridge cleavage as a minor metabolic route. HED has determined that the residue of concern (ROC) for tolerance enforcement and risk assessment is the parent

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/

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 12 of 36 compound (rimsulfuron) for plants and livestock commodities.

Table 5 .1. Compounds to be Included in the Rimsulfuron Risk Assessment and Tolerance Expression.

Matrix Residues included in Risk
Assessment Residues included in Tolerance Expression

Plants Primary Crop Rimsulfuron Rimsulfuron

Rotational Crop Rimsulfuron Rimsulfuron

Livestock Ruminant Rimsulfuron Rimsulfuron

Poultry Rimsulfuron Rimsulfuron
Drinking Water Rimsulfuron , IN

- 70941 and IN

- 70942 Not Applicable



### The residue chemistry database is adequate to support current Registration Review data requirements. Adequate metabolism, field trial and processing studies are available to support the registered uses. The magnitude of the residue and processing studies are supported by adequate storage stabilit y data for rimsulfuron. Adequate methods are available for enforcement of the currently established tolerances. Based on the registered ruminant feed items, there is no reasonable expectation of finite residues of rimsulfuron in livestock commodities. A dequate confined rotational crop data are available to support minimum plant

- back intervals up to 18 months, depending on the end

- use product.

Adequate high performance liquid chromatography methods with tandem mass spectroscopic detection (HPLC/MS/MS) are available for tolerance enforcement: Method DuPont

- 15033 for watery and dry crop matrices, Method DuPont

- 15027 for oily crop matrices; DuPont

- 17928 for grass, and DuPont

- 32277 for sorghum commodities. The validated limit of quantitation (LOQ) is 0.010 ppm in each matrix. An HPLC/UV (ultraviolet) method is available for tolerance enforcement for residues of rimsulfuron in/on corn, potato, and t omato commodities. The LOQ is 0.05 ppm. The methods have been adequately validated for the determination of residues of rimsulfuron in plants.

Multi

- residue methods testing data were previously submitted for rimsulfuron, which indicated
that the methods are not applicable for rimsulfuron determination.

An analytical reference standard for rimsulfuron with an expiration date of 03/10/2020 is available at EPA’s National Pesticide Standards Repository (e

- mail dated 05/11/2015 from Theresa Cole, Analytical Chemistry Branch/Biological and Economic Analysis Division).

The structure, physical/chemical properties, and structure of metabolites are summarized in Appendix B.

5.2 Water Residue Profile

Rimsulfuron foliar applications using ground and aerial sprays impact both surface water and ground water drinking sources given that it possesses similar physical chemical properties and persistence to other chemicals which are known to translocate to these media. The drinking water residues used in the dietary asses sment were provided by the Environmental Fate and Effects Division (EFED) in the following memorandum: “Tier I Drinking Water Assessment for the proposed Section 3 ALS inhibition tolerant sorghum crops new use for the chemical

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 13 of 36 Rimsulfuron”; (M. Barrett, D4 14506, 03/13/2014) and were incorporated directly into the dietary assessment. Water residues were incorporated in the DEEM Food Commodity Intake Database (FCID) into the food categories “water, direct, all sources” and “water, indirect, all sources.”

Estimated drinking water concentrations (EDWCs) include total toxic residues of rimsulfuron
and its degradates (IN

- 70941 and IN

- 70942) in accordance with the most recent memo of the Residues of Concern Knowledgebase Subcommittee (ROCKS; C. Walls, D416833, 12/18/2013).
The estimate s are based on the assessment of all registered uses using the Tier 1 model PRZM

GW (Pesticide Root Zone Model

- Ground Water). The maximum EDWC s are presented below
in Table 5.2

.

Table 5.2

. Maximum Tier I Rimsulfuron EDWCs for dr inking water based on application of rimsulfuron to crops with highest rates and exposure potential. 1

Crops (scenario) Highest Daily Value (Acute) Post

- Breakthrough Average (Chronic and Cancer)

All 22.2 19.7

1 Based upon the highest values from six standard Tier 1 groundwater scenarios (i.e., a WI scenario based upon a predominantly corn production area). The EDWCs are representative for all registered crop use sites

.



### 5.3 Dietary (Food + Water) Exposure Assessment

HED recently conducted an unrefined chronic dietary (food and drinking water) assessment for rimsulfuron (D418154, M. Negussie, 03/17/2014). The assessment was based on the assumption that rimsulfuron residues are present at tolerance levels in all commod ities for which tolerances have been established and that 100% of those crops are treated. DEEM Version 7.81 default processing factors were applied to all processed commodities for which they were available. The groundwater EDWC of 19.7 μg/L from the Ti er I PRZM

- GW modeling was incorporated directly into the dietary assessment.

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

con sumption data from the 2003

- 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 conce rned when the dietary exposure estimates exceed 100% of the acute or chronic population adjusted dose (aPAD or cPAD). The chronic dietary (food and drinking water) exposures to rimsulfuron are below HED’s level of concern (i.e., <100% of the aPAD or cPAD) for the general U.S. population and all population subgroups. The chronic dietary exposure estimates are <1% of the cPAD for the general U.S. population and 1.4% of the cPAD for infants (<1 year old), the most highly exposed population subgroup. Because of the conservative assumptions used in the analyses (tolerance level residues, 100% crop treated, default processing factors, and upper

- bound modeled drinking water estimates) , actual exposures and risks are expected t o be lower than shown in Table 5.3

. HED did not conduct an acute dietary exposure/risk assessment because an acute dietary POD was not selected for rimsulfuron. Rimsulfuron is considered “not likely to be carcinogenic to

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 14 of 36 humans”; therefore a cancer dietary risk assessment was also not con ducted.

Table 5.3 . Chronic Aggregate Dietary (Food + Drinking Water) Exposure and Risk for
Rimsulfuron

.

Population Subgroup Exposure (mg/kg/day) % cPAD

General U.S. Population 0.000807 <1
All Infants (< 1 year old) 0.001710 1.4

Children 1

- 2 years old 0.001658 1.4

Children 3

- 5 years old 0.001473 1.2

Children 6

- 12 years old 0.001002 <1

Youth 13

- 19 years old 0.000724 <1

Adults 20

- 49 years old 0.000743 <1

Adults 50

- 99 years old 0.000652 <1

Females 13

- 49 years old 0.000724 <1



### 6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

There are registered uses of rimsulfuron on sod farms, and golf courses; therefore, there is potential for post

- application dermal exposure for adults and children. However, a quantitative residential post

- application risk assessment was not conducted bec ause there was no hazard identified for rimsulfuron via the dermal route of exposure.

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 de posit 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 indirect exposures ( e.g. , children playing on lawns where resid ues 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 language and other regulatory requi rements intended to prevent them. 1 

### 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 areas, 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

1 This approach is consistent with the requirements of the EPA’s Worker Protection Standard.

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 15 of 36 exposure are the fo cus 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 us es 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 rimsulfuron

. In the spray drift scenario, the deposited residue val ue 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 Procedures Addenda 1: Consideration of

S pray 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 Procedures For Residential Risk Asses sment (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. 1 

### AgDrift is appropriate for use only when 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 agricultur e. These screening options are 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 evalua ted 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 many 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 d rift deposition fractions were also considered. These drift estimates represent plausib le options for pesticide labels.

6.1.1 Incidental Oral 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. Rimsulfuron is registered on multiple agricultural use sites, as well as on non

- agricultural use sites, including sod farms, non

residential turf (incl uding professional and college sports fields, commercial turf), golf courses, roadsides, industrial sites, utility substations, rangeland, and other non

- crop sites. Rimsulfuron may be applied using groundboom

, aerial , chemigation, and handheld application equipment. The recommended drift scenario screening level options are listed below:

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

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 16 of 36  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 applicatio ns 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/dri ft event). 1



### I ncidental oral risk estimate s from drift onto residential areas were evaluated for rimsulfuron using the maximum registered application rate of 0.063 lb ai/A. This is protective of all the registered uses of rimsulfuron at lower application r ates. The applicable LOC is 100; therefore
MOEs < 100 are of concern. Adult and children 1 to <2 year old dermal risk estimates were not
calculated because there was no dermal hazard identified in the rimsulfuron database. Children’s (1 to <2 year old) incidental oral risk estimates from indirect exposure to rimsulfuron

- related to spray drift result in no risks of concern at field edge.

Table 6.1 . Children 1 to <2 Years Old Incidental Oral Risk Estimates (MOEs) Related to Spray Drift Exposure to Rimsu lfuron 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)

Agricultural Applications 1

Aerial Fine to Medium

0.063 0.0070 25,000

Groundboom High Boom Very fine
to Fine 35,000

1 Maximum registered application rate of rimsulfuron. This assessment is considered protective of all registered crops and use sites with lower 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 agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Roden ticide 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. 2 

### During Registration Review, the agency will

1 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 patt ern it should be used as the screening criteria and deposition values associated with it are 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.

2 A vailable at: http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219

.

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 17 of 36 utilize this analysis to determine if data (i.e., flux studies, route

- specific inhalation toxicological studies) or further analysis is requir ed for rimsulfuron

.

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
ther e is reliable information. In the case of rimsulfuron, aggregate exposure and risk estimates are equivalent to the dietary exposure and risk estimates in Section 6 and are not of concern. There are no registered uses for rimsulfuron that will result in d irect non

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

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

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

8.0 Occupational Exposure/Risk Characterization

There is potential occupational dermal and inhalation exposure from the registered uses of rimsulfuron. However, there was no dermal hazard identified in the rimsulfuron toxicity database; therefore only inhalation risk estimates were calculated.

8.1 Occupational Handler

8.1.1 Occupational Handler Exp osure , Assumptions and Risk Estimate Equation s

A pplication Rate : The maximum single application rates are listed in Table 8 .1 . Refer to
S ection 3 .0 for a complete use pattern description.

Body Weight & Absorption Factor : 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 equivalent to the estimated toxicity by the oral route of exposure.

Unit Exposur es: 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, and the AHETF database. Some of these data are pro prietary (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 exposures”, are outlined in the “Occupational Pest icide Handler Unit Exposure Surrogate

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 18 of 36 Reference Table 1 

### .” HED policy on use of surrogate data, including descriptions of the various sources, can be found at the Agency website 2



### .

Area Treated : The area treated inputs were based on the Science Advisory Council for Exposure Policy 9.1: Standard Values for Daily Acres Treated in Agriculture (listed in Table 8 .1 ).

Risk Estimate Equations : The algorithms used to estimate non

- cancer exposure and d ose for occupational handlers can be found in Table 8

. 1

.

8.1.2 Summary of Occupational Handler Non

- Cancer Exposure and Risk
Estimate

All occupational handler scenarios for the registered uses resulted in MOEs greater than 100 at baseline level of risk mitigatio n (i.e., baseline attire with no gloves or respirator) or engineering control for aerial applications (i.e., enclosed cockpits) ; therefore, are not of concern. The lowest
inhalation MOE of 790 is associated with mixing/loading a dry flowable formulation f or aerial application to high acreage field crops; such as corn or soybeans

. The Agency matches quantitative occupational exposure assessment with appropriate characterization of exposure potential. While HED presents quantitative risk estimates for huma n flaggers where appropriate, agricultural aviation has changed dramatically over the past two decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of their membership, the use of GPS for swath guidance in agricultural aviat ion has grown steadily from the mid 1990’s. Over the same time period, the use of human flaggers for aerial pesticide applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent (2012) NAAA survey. The Agency will continu e to monitor all available information sources to best assess and characterize the exposure potential for human flaggers in agricultural aerial applications.

HED has no data to assess exposures to pilots using open cockpits. The only data available is for exposure to pilots in enclosed cockpits. Therefore, risks to pilots are assessed using the engineering control (enclosed cockpits) and baseline attire (long

- sleeve shirt, long pants, shoes, and socks); per the Agency’s Worker Protection Standard stipulat ions for engineering controls, pilots are not required to wear protective gloves for the duration of the application. With this level of protection, there are no risk estimates of concern for applicators.

1 Available at: http://www.epa.gov/opp00001/science/handler

- exposure

- table.pdf

2 Available at: http://www.epa.gov/pesticides/science/handler

- exposure

- data.html

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 19 of 36 Table 8

. 1 . Occupational Handler Short

- and Interm ediate

- Term Non

- Cancer Exposure and Risk
Estimates for Rimsulfuron

.

Exposure Scenario Crop or Target Level of
Concern Inhalation

Unit Exposure (μg/lb ai) 1 Maximum

Application

Rate 2 Area

Treated or
Amount

Handled Daily 3 Inhalation

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

Mixer/Loader

Mixing/Loading Dry
Flowables for Aerial Application Sod

100 8.96 0.031 lb ai/A 350 acres 0.00122 5,100

Field Crop, Typical 6 0.063 lb ai/A 350 acres 0.00248 2,500

Field Crop, High Acreage 7 0.063 lb ai/A 1200 acres 0.00846 740

Mixing/Loading Dry Flowables for Chemigation Application Orchard/Vineyard 8 0.063 lb ai/A 350 acres 0.00248 2,500

Field Crop, High Acreage 7 0.063 lb ai/A 350 acres 0.00248 2,500

Mixing/Loading Dry
Flowables for Groundboom Application Golf Course 0.031 lb ai/A

40 acres 0.000139 45,000

Field

- Grown Ornamental Crops 1 0 0.063 lb ai/A 0.000283 22,000

Sod 0.031 lb ai/A 80 acres 0.000278 22,000

Orchard/Vineyard 8

0.063 lb ai/A 40 acres 0.000283 22,000

Field Crop, Typical 6 80 acres 0.000565 11,000

Field Crop, High Acreage 7 200 acres 0.00141 4,400

Mixing/Loading Liquids for Aerial Application Field Crop, High Acreage 7

0.219 0.0079 lb
ai/A 1200 acres 0.000026 240,000

Mixing/Loading Liquids
for Groundboom Application 200 acres 0.00000433 1,400,000

Mixing/Loading Liquids for Backpack and Mechanically Pressurized Handgun Application Rights of Way

0.0063 lb ai/gal 1000 gal 0.0000173 360,000

Mixing/Loading Dry
Flowables for Backpack and Mechanically Pressurized Handgun Application Rights of Way 8.96 0.000705 8,900

Applicator

Applying Sprays via Aerial Equipment Sod

100 0.0049 0.031 lb ai/A 350 acres 0.00000067 9,400,000

Field Crop, Typical 6

0.063 lb ai/A 0.00000135 4,600,000

Field Crop, High Acreage 7 1200 acres 0.00000463 1,300,000

Applying Sprays via Groundboom Equipment Golf Course

0.34 0.031 lb ai/A

40 acres 0.00000528 1,200,000

Field

- Grown Ornamental Crops 1 0 0.063 lb ai/A 0.0000107 580,000

Sod 0.031 lb ai/A 80 acres 0.0000105 600,000

Orchard/Vineyard 8 0.063 lb ai/A 40 acres 0.0000107 580,000

Field Crop, Typical 6 0.063 lb ai/A 80 acres 0.0000214 290,000

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 20 of 36 Table 8

. 1 . Occupational Handler Short

- and Interm ediate

- Term Non

- Cancer Exposure and Risk
Estimates for Rimsulfuron

.

Exposure Scenario Crop or Target Level of
Concern Inhalation

Unit Exposure (μg/lb ai) 1 Maximum

Application

Rate 2 Area

Treated or
Amount

Handled Daily 3 Inhalation

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

Field Crop, High Acreage 7 0.063 lb ai/A 200 acres 0.0000535 120,000

Applying Sprays via Mechanically Pressurized Handgun Rights

- of

- Way 8.68 0.0063 lb ai/gal 1000 gal 0.000684 9,100

Flagger

Flagging for Aerial Application Sod

100 0.35 0.031 lb ai/A

350 acres 0.0000475 130,000

Field Crop, High Acreage 7 0.063 lb ai/A 0.0000965 65,000

Mixer/Loader/Applicator

Mixing/Loading/Applying Sprays via Backpack Sprayers Orchard/Vineyard 8

100 2.58 0.0063 lb
ai/A

40 gal 0.00000813 770,000

Landscaping, T urf (athletic fields, parks, etc) 11 0.0021 lb ai/gal 0.00000271 2,300,000

Industrial/Commercia
l Areas

30 0.0063 lb ai/gal 0.0000945 66,000

Mixing/Loading/Applying Sprays via Manually
Pressurized Handwand Landscaping, T urf (athletic fields, parks, etc) 11 0.0021 lb ai/gal 40 gal 0.0000315 200,000

Industrial/Commercia
l Areas 0.0063 lb ai/gal 0.0000945 66,000

Mixing/Loading/Applying Sprays via Mechanically Pressurized Handgun Orchard/Vineyard 8 3.9 0.0063 lb ai/gal 1000 gal 0.000308 20,000

Golf Course 42 0.021 lb ai/A 5 acres 0.0000551 110,000

Landscaping, T urf (athletic fields, parks, etc) 1 1 42 0.021 lb ai/A 5 acres 0.0000551 110,000

Industrial/Commercia
l Areas 3.9 0.0063 lb ai/gal 1000 gal 0.000308 20,000

Field Crop, Typical 6 3.9 0.0063 lb ai/gal 1000 gal 0.000308 20,000

Loader/Applicator

Loading/Applying Dry Flowables and Liquids for Backpack Application Rights of Way 100 69.1 0.0063 lb ai/gal 40 gal 0.000218 29,000

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

2 Based on registered rimsulfuron label s

. 3 Exposure Science Advisory Council Policy #9.1.

4 Inhalation Dose = Inh alation 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).

5 Inhalation MOE = Inhalation NOAEL ( 6.25 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 21 of 36 6 “F ield Crop, Typical” represents registered crops such as cranberries and tomatoes

. 7 “Field Crop, High Acreage” represents registered crops such as corn, soybeans. Assessment is protective of other high acr eage field crops with lower application rates, su ch as potatoes, peanuts, cotton, and chicory. 8 “Orchard/Vineyard” represents registered crops such as citrus, stone fruit, tree nuts, pome fruit, grapes, blueberries and cranberries. 9 “Field Crop, High Acreage” for liquids only registered for use on field corn. 10 “Field Grown Ornamental Crops” to represent field grown tomatoes and tomatoes grown for transplanting.

11 Rimsulfuron is not registered for use on residential turf, but is registered for use on athletic fields and non

- residential areas.



### 8.2 Occupational Post

- Application Exposure

8.2.1 Occupational Inhalation Post

- Application Exposure

HED uses the term post

- application to describe exposures that occur when individuals are present in an environment that has been previously treated with a pesticide (also referred to as re

entry exposure). Such exposures may occur when workers enter previously treated areas to perform job fun ctions, including activities related to crop production, such as scouting for pests or harvesting. Post

- application exposure levels vary over time and depend on such things as the type of activity, the nature of the crop or target that was treated, the ty pe of pesticide application, and the chemical’s degradation properties. In addition, the timing of pesticide applications, relative to harvest activities, can greatly reduce the potential for post

- application exposure.

There are multiple potential sources 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 pesticides. 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, 201 0 ( 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 toxicological studies) or further analysis is required for rimsulfuron

. 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 occupati onal post

- application inhalation exposure into the agency's risk assessments.

Although a quantitative occupational post

- application inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercia l 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 o ccupational post

- application inhalation exposure scenarios.

8.2.2 Occupational Post

- application Dermal Exposure Data and Assumptions

An occupational post

- application dermal exposure assessment was not performed for rimsulfuron

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 22 of 36 because no dermal hazard was identi fied in the toxicity database. Therefore, an assessment of occupational dermal post

- application exposure to rimsulfuron was not conducted. A chemical

specific DFR study is not available for rimsulfuron and is not required at this time ( Appendix E ).

8.2.3 Re stricted Entry Interval

Based on the acute toxicity categories and post

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

- hours. REIs may be further reduced if certai n criteria are met in accordance with the Pesticide Registration (PR) Notice 95

- 3 [Reduction of WPS Interim REIs for Certain Low Risk Pesticides] 1 

### . In PR Notice 95

- 3, there are a set of criteria listed for the active ingredient that
must be met for chemic als 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 tox icity data were used if 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 (ana logs), and excluded such 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 ingred ients, no known reports 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 serio us neurological effects.

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 a ppropriate chemical and 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 ris k is considered appropriate), 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'' rela ted to post

- application exposures to the active ingredient.

Upon review of the criteria for the active ingredient only , it appears that rimsulfuron is consistent
with the criteria in PRN 95

- 3 that allow for a 4

- hour REI. Note : The PR Notice also includes similar

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

- 3.html

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 23 of 36 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 rimsulfuron.

9.0 Cumulative Exposure/Risk Ch aracterization

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 available toxicological information and if necessary, followed by a risk

- based screening approach. This framework supplements the existing guidance documents for establishing common me chanism 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 toxicolog ical 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.

10.0 Public Health and Pesticide Epidemiology Data

Evaluation of the OPP Incident Data System (IDS) (S. Recore, D 402251, 5 / 8 /12 ; include s incidents from January 1, 2007 through February 22, 2012 ) indicated that no single chemical
rim sulfuron incidents were identified in the United States. In the aggr egate IDS ( which reports incidents of multiple chemical exposures at the same time) there were 9 incidents reported for
rim sulfuron . Because they fall within the categories reported as counts (which includes minor, unknown or no effects), there is no uniq ue report that provides details about the incident and single chemical incidents are not distinguished from multiple chemical incidents

. A high frequency of incidents indicates there is a high potential for exposure and vice versa. However
f or rims ulfuro n, there appears to be a low potential for exposure. Rim sulfuron is not included in the Agricultural Health Study (AHS), and therefore, the AHS does not provide information for this report. There does not appear to be a concern at this time that would wa rrant further investigation. The Agency will continue to monitor the incident information. If a concern is triggered, additional analysis will be included in the risk assessment.

1 http://www.epa.gov/oppfead1/cb/csb_page/updates/2015/framew 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)

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 24 of 36 11.0 References

Author Barcode Date Title

J. Van
Alstine TXR

0050008 0 4/26/2012 Rimsulfuron: Summary of Hazard and Science Policy Council

(HASPOC) Meeting of March 29, 2012: Recommendations on the
need for a 28

- day dermal toxicity study.

S. Recore D402251 05/08/2012 Rimsulfuron: Review of Human Incidents

K. Rury TXR

005643 8 0 9/17/2012 Rimsulfuron: Summary of Hazard and Science Policy Council

(HASPOC) Meeting of August 9, 2012: Recommendations on the Requirement of Repeated Exposure Inhalation Study.

C. Walls D416833 12/18/2013 Rimsulfuron: Environmental Degradates Found in Drinking Water

M. Barrett D414506 03/13/2014 Tier I Drinking Water Assessment for the proposed Section 3 ALS inhibition tolerant sorghum crops new use for the chemical
Rimsulfuron

M

. Negussie D418154 03/17/ 20 14 Rimsulfuron Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessment for the Section 3 Registration on Acetolactase Synthase (ALS) Tolerant Grain Sorghum.

C. Walls D408722 0 7/ 0 2/2014 Rimsulfuron. Human Health Risk Assessment for P roposed Section 3 Use on Acetolactase Synthase (ALS) Tolerant Grain Sorghum.

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 25 of 36 A ppendix A . Toxicology Profile

A.1 Toxicology Data Requirements

Table A.1. Rimsulfuron Data Requirements

Test Technical
Required Satisfied

870.1100 Acute Oral Toxicity

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

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

................................ ............. 870.2400 Primary Eye Irritation

................................ ................... 870.2500 Primary Dermal Irritation

................................ ............. 870.2600 Dermal Sensitization

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

yes

yes

yes

yes

yes y es

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)

................................ .............. 870.3150 Oral Subchronic (nonrodent)

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

- Day Dermal

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

- Day Dermal

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

- Day Inhalation

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

yes

yes

no

yes yes

yes waived 1

--- waived 2

870.3700 Developmental Toxicity (rodent)

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

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

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

yes

yes yes

yes

yes

870.4100 a Chronic Toxicity (rodent)

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

................................ ....... 870.4200 a Carcino genicity (rat)

................................ ..................... 870.4200 b Carcino genicity (mouse)

................................ ............... 870.4300 Chronic Toxicity/Carcino genicity (rodent)

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

yes

yes

yes

no yes 3

yes

yes 3

yes

yes 3

870.5100 Mutagenicity

— Gene Mutation

- bacterial

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

— Gene Mutation

- mammalian

............... 870.53 8 5 Mutagenicity

— Structural Chromosomal Aberrations

.. 870.5 550 Mutagenicity

— Other Genotoxic Effects

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

yes

yes

yes yes

yes

yes

yes

870.6100 Acute Delayed Neurotox. (hen)

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

- Day Neurotoxicity (hen)

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

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

- Day Neurotoxicity Screening Battery (rat)

.............. 870.6300 Developmental Neuro toxicity

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

no

yes

yes

no ---

---
yes

yes

---

870.7485 General Metabolism

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

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

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

no

yes y es

---
yes

1 The requirement for this study has been waived ( J. Van Alstine, TXR 0050008, 4/26/2012).

2 The requirement for this study has been waived ( K. Rury, TXR 0056438, 9/17/2012).

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

.

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 26 of 36 A.2 Toxicity Profiles

Table A.2.1. Acute Toxic ity Profile

– Rimsulfuron

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

870.1100 Acute oral

– rat 41356311, 41356310,
41931634 LD 50 > 5000 mg/kg IV

870.1100 Acute oral

– mouse 41931623 LD 50 > 5000 mg/kg IV

870.1200 Acute dermal

– rabbit 41356312, 41356313, 41931624, 41931635 LD 50 ≥ 2000 mg/kg III

870.1300 Acute inhalation

– rat 41356314, 41931625, 41931637, 41931636 LC 50 ≥ 7.5 mg/L IV

870.2400 Acute eye irritation

–

rabbit 41931626, 41356315, 41356316, 41931638 Moderate eye

irritant III

870.2500 Acute dermal irritation

–

rabbit 41931627, 41356318 41931639, 41356317 Not an irritant IV

870.2600 Skin sensitization

–

guinea pig 41931628, 41356320, 41931641, 41931640,
41356319 Not a sensitizer NA



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

– Rimsulfuron

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

Classification /Doses Results

870.3100

90

- Day Oral Toxicity in Rodents (rat) 41356321 (1989) Acceptable/guideline 0, 50, 1500, 7500, 2000 ppm 0, 2.5, 75, 375, 1000 mg/kg/day NOAEL = 75 mg/kg/day

LOAEL = 375 mg/kg /day based on reduced body

w eigh t gains.

870.3100

90

- Day Oral Toxicity in Rodents (mouse) 41356323 (1989) Acceptable/ non

- guideline
0, 50, 375, 500, 7500 ppm 0, 7.5, 56, 225, 1125 mg/kg/day NOAEL = 56 mg/kg/day males; >1125 females.

LOAEL = 225 mg/kg /day based on increased RBC and hemoglobin and decreased body weight gain and
food efficiency in males (not established in females).

870.3150

90

- Day Oral Toxicity in nonrodent (dog) 41356322 (1989) Acceptable/guideline
0, 250, 5000, 20000 ppm
0, 6. 25 , 125, 500 mg/kg/day NOAEL = 6. 25 mg/kg/day LOAEL = 125 mg/kg/day based on increased urinary volume and kidney weights and decreased osmolality.

870.3700a Prenatal developmental in rodent (rat) 41356324 (1989) Acceptable/guideline
0, 200, 700 , 2000 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) 41356325 (1989) Acceptable/guideline
0, 25, 170 , 500 or 1500 mg/kg/day Materna l NOAEL = 170 mg/kg/day LOAEL = 500 mg/kg/day based on death and reduced weight gain.
Developmenta l NOAEL = 500

LOAEL was not observed. O nly two viable fetuses
were available for evaluation at 1500 mg/kg bw/day.

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 27 of 36 Table A.2.2 Subchronic, Chronic and Other Toxicity Profile

– Rimsulfuron

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

Classification /Doses Results

870.3800
Reproduction and Fertility Effects (rat) 41931644 (1990)
Acceptable/guideline
0, 50, 3000, 15000 ppm

M: 0, 2.8, 165, 830 F: 0, 3.4 , 204, 1021 mg/kg/day (F 0 )

M: 0, 3.7, 217, 1316 F: 0, 4.3 , 264, 1316 mg/kg /day (F 1 ) Parental/Systemic NOAEL = 165 mg/kg/day

LOAEL = 830 mg/kg/day based on decreased body weight and/or body weight gain in both sexes and generations

. Reproductive NOAEL = 1316 mg/kg/day

LOAEL could not be established.
Offspring NOAEL = 264 mg/kg/day

LOAEL = 1316 mg/kg/ day based on decreased body weight in F 2 female pups on PND 7 and PND 14.

870.4100
Chronic toxicity (dog) 41931643 (1991)
Acceptable/guideline
0, 50, 2500, 10000 ppm

M: 0, 1.6, 82, 342; F: 0, 1.6, 87, 359 mg/kg/day NOAEL = 82 mg/kg/day
LOAEL = 342 mg/kg/day based on decreased female body weight; increased liver and kidney weights (both sexes); increased female serum cholesterol and

ALP levels; increased incidence of seminiferous tubule degeneration and incr eased numbers of spermatid giant cells in epididymides in males

.

870.4200
Carcinogenicity (mouse) 4931642 (1991)
Acceptable/guideline
0, 25, 250, 2500, 7500 ppm

M: 0, 3.5, 36, 351, 1127; F: 0, 5.0, 51, 488, 1505 mg/kg/day NOAEL = 351 mg/kg/day

LOAEL = 1127 mg/kg/day based on decreased body weight (both sexes); increased incidence of glandular stomach dilation and cysts in males; testicular artery and tunica albuginea degeneration in males

. No evidence of carcinogenicity.

870.4300

Ch ronic Toxicity/Carcinogenicity (rat) 42047701 (1991)
Acceptable/guideline
0, 25, 300, 3000 or 10000 ppm

M: 0, 1.0, 12, 121, 414; F: 0, 1.4, 17, 163, 568 mg/kg/day NOAEL = 12/163 mg/kg/day (male/female)
LOAEL = 121/568 based on decreased body weight gain and increased liver weight

. No evidence of carcinogenicity.

870.5100

Bacterial Reverse Mutation

Test Salmonella typhimurium and/or E. coli ) 4 2471310 (1992)
Acceptable/guideline

0, 10, 25, 50, 75, 100, 500, 750, 1000 or 5000 μg/plate DPX

- E9636

- 22 was tested up to the limit concentration and was not mutagenic in the assay
either with or without S

- 9 activation. The positive controls induced the appropriate responses in the corresponding strains.

870.5300

In vitro Mammalian Cell
Gene Mutation Test (Chinese hamster ovary cells) 41356328 (1989)
Acceptable/guideline

0, 10, 100, 250, 750 or 1300 μg/mL DPX

- E9636

- 22 tested up to the limit of solubility. The positive controls induced the appropriate response. There was no evidence of induced mutant colonies over background.

870.5375

In vitro Mammalian
Chromosome Aberration

Test (human lymphocytes) 41356329 (1989)
Acceptable/guideline
0, 100, 600, 1000 or 1300 μg/ml DPX

- E9636

- 22 tested up to the precipitating
concentration . Positive controls induced the appropriate response. There was no evidence of Chromosome aberration induced over background.

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 28 of 36 Table A.2.2 Subchronic, Chronic and Other Toxicity Profile

– Rimsulfuron

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

Classification /Doses Results

870.5385

Mammalian Bone Marrow
Chromosome Aberration Assay (mouse) 41931622 (1989)
Acceptable/guideline
0, 500, 3000 or 5000 mg/kg Compared to the vehicle control, no significant differences in the frequency of micronucleated cells
were noted in the bone marrow cells from the animals treated with test compound.

870.5395
Mammalian Erythrocyte Micronucleus Test (mouse) 41356330 (1989)
Acceptable/guide line
0, 500, 3000 or 5000 mg/kg DPX

- E9636

- 22 tested up to the limit dose. P ositive control induced appropriate response. No significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow after any treatment time.

870.5550
Other Genotoxicity:
Unschedule d D Synt hesis (primary rat hepatocytes) 41356327 (1989)
Acceptable/guideline

0, 0.0008, 0.004, 0.008, 0.04, 0.08, 0.4, 0.8, or 1.1 mg/mL DPX

- E9636

- 22 tested up to limit its concentration

. The positive controls induced the appropriate response. There was no evidence that unscheduled D synthesis was induced.

870.6200a
Acute Neurotoxicity Screening Battery (rat) 48710302 (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) 48710303 (2011)
Acceptable/guideline
0, 1000, 3000, 75000 ppm

M: 0, 55, 170 or 438; F: 0, 69, 193, 507 mg/kg/day NOAEL = 438 mg/kg/day

LOAEL could not be established.

870.7485

Metabolism and Pharmacokinetics (rat) 42540701 (1989)
Acceptable/guideline
Single dose oral: 25 or 250 mg/kg
Repeated dose oral: 25 mg/kg/day for 15 days No remarkable differences in excretion pattern between

sexes. > 90% dose excreted within 72 hours. Elimination: urine ~64% dose, feces ~30%, exhaled air <0.08%. Low but detectable amounts in heart, lung, liver, kidney, and muscle; repeat dose groups also showed accumulation in spleen. Hepatic accumulation, although low , slightly higher than other organs. Males
showed more liver accumulation than females. Most urinary (42

- 55%) and fecal (5

- 16%) excretion was parent compound. Metabolism largely involved either contraction or cleavage of sulfonylurea bridge, followed by de methylation and subsequent hydroxylation.

870.7800
Immunotoxicity (female mouse) 48 710305 (2011)
Acceptable/guideline
0, 300, 600, 1800 or 6500 ppm
0, 45, 93, 288, 1006 mg/kg/day NOAEL = 1006 mg/kg/day

LOAEL could not be established.

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 29 of 36 Appendix B. Physical/Chemical Properties of Rim sulfuron and Metabolites

Table B.1. Rimsulfuron Nomenclature.

Compound

Common name Rimsulfuron
Company experimental name DPX

- E9636

IUPAC name 1

- (4,6

- dimethoxypyrimidin

- 2

- yl)

- 3

- (3

- ethylsulfonyl

- 2

- pyridylsulfonyl)urea

CAS name N

- [[(4,6

- dimethoxy

- 2

- pyrimidinyl)amino]carbonyl]

- 3

- (ethylsulfonyl)

- 2

- pyridinesulfonamide
CAS registry number 122931

- 48

- 0
An analytical reference standard for rimsulfuron with an expiration date of 03/10/2020 is available at EPA’s National Pesticide Standards Repository (e

- mail dated 05/11/2015 from Theresa Cole, Analytical Chemistry Branch/Biological and Economic Analysis Division).

Table B.2. Physicochemical Properties of Technical Grade Rimsulfuron.

Parameter Value Reference
Melting point 172

- 173  C Reviewed in DP# 193018, M. Nelson, 23/NOV/1993; Also, MRID No.
47572805. All product chemistry requirements reported to
be fulfilled. pH 4.32 to 5.89 (1% dilution in water)
Density 1.5032 ± 0.0016 g/cm 3

Water solubility pH 5: 0.135 ± 0.005 g/L (25°C) pH 7: 7.3 ± 0.03 g/L (25  C) pH 9: 5.56 ± 0.05 g/L (25  C) pH 4

- 4.5: 0.024 ± 0.001 g/L (20  C)
Solvent solubility (25°C) N,N

- dimethylformamide 241 ± 1 g/L Dimethyl sulfoxide 113 ± 3 g/L Methylene chloride 35.5 ± 0.4 g/L
Acetonitrile 17.2 ± 0.5 g/L

Acetone 14.8 ± 0.5 g/L Ethyl acetate 2.85 ± 0.17 g/L
Methanol 1.55 ± 0.11 g/L
Toluene 0.363 ± 0.022 g/L Xylene 0.093 ± 0.008 g/L

n

- Hexane <0.01 g/L
Vapor pressure (25°C) <10

- 5 Pa
Dissociation constant, pK
a 4
Octanol/water partition coefficient, Log(K OW ) pH 5: 1.94 pH 7: 0.0342 pH 9: not attempted
UV/visible absorption
spectrum pH 1.80 at 230 nm, ε = 1.78 x 10 4 (log ε = 4.25) and at 290 mm, ε = 1.81x 10 2 (log ε = 2.26)
pH 2.10 at 290 nm, ε = 2.03 x10 2 (log ε = 2.31)
pH 5.03 at 240 nm, ε = 2.24 x 10 4 (log ε = 4.35) and at 290 nm, ε = 4.81 x 10 2 (log ε = 2.68)

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 30 of 36 Table B.3. Chemical Names and Structures for Rimsulfuron Metabolites

Company code; Chemical name Chemical structure

IN

— 70941

N

- (4 ,6

- Dimethoxy

- 2

- pyrimidinyl)

- N

- ((3

- ethylsulfonyl)

- 2

- pyridinyl)

urea

IN

- 70942

N

- ((3

- ethylsulfonyl)

- 2

- pyridinyl)

- 4,6

- dimethoxy

- 2

- pyrimidinamine

IN

- E9260
3

- (Ethylsulfonyl )

- 2

- pyridinesulfonamide.

IN

- T5831

N

- (4,6

- dimethoxy

- 2

- pyrimidinyl)urea

IN

- 69190

2

- amino

- 4,6

- dimethoxy

- 5

- pyrimidinol

IN

- J290

2

- Amino

- 4,6

- dimethoxypyrimidine

IN

- H1043

2

- Amino

- 4,6

- dihydroxypyrimidine

IN

- JF999

N

- [((3

- Ethylsulfonyl)

- 2

- pyridinyl)]

- 4

- hydroxy

- 6

- methoxy

- 2

- pyrimidineamine

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 31 of 36 Appendix C

. 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 che mical. These data are subject to ethics review pursuant to 40 CFR 26, have received that review, and are compliant with applicable ethics requirements. For certain studies that review may have included review by the Human Studies Review Board. Descripti ons 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

.

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 32 of 36 Appendix D

. International Harmonization

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

Residue Definition:

US Canada Mexico 1 Codex

40 CFR 180. 478 : (a) General: rimsulfuron, N

- ((4,6

- dimethoxypyrimidin

2

- yl)aminocarbonyl)

- 3

- (ethylsulfonyl)

- 2

- pyridinesulfonamide) N

- [[(4,6

- dimethoxy

- 2

- pyrimidinyl)amino]carbonyl]

- 3

- (ethylsulfonyl)

- 2

- pyridinesulfonamide None

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

US Canada Mexico 1 Codex Almond, hulls 0.09 Bushberry, subgroup 13

- 07B 0.01 0.01 aronia berries, buffalo currants, Chilean guavas, currants, elderberries, European barberries, gooseberries, highbush blueberries

, highbush cranberries honeysuckle, huckleberries

, jostaberries, lingonberries, native currants, salal berries, saskatoon ber ries (juneberries), sea buckthorn

0.05 lowbush blueberries Caneberry, subgroup 13

- 07A 0.01
Chicory, roots 0.01
Chicory, tops 0.01
Corn, field, forage 0.4
Corn, field, grain 0.1 0.1 field corn

Corn, field, stover 2.5

Fruit, citrus, group 10 0.01
Fruit, pome, group 11 0.01
Fruit, stone, group 12 0.01
Grain, aspirated fractions 4.5
Grape 0.01
Nut, tree, group 14 0.01

Pistachio 0.01

Potato 0.1 0.1 potatoes
Soybean, forage 0.25
Soybean, hay 1.2
Soybean, hulls 0.04
Soybean, seed 0.01

Tomato 0.05 0.05 tomatoes

Recommended Tolerances (DP# D418153) Sorghum, grain, grain 0.01 Sorghum, grain, forage 0.01 Sorghum, grain, stover 0.01

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

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 33 of 36 Appendix E . DFR and TTR Data Waiver Rationale

Dislodgeable Foliar Residue (DFR): In accordance with 40CFR158, 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

- specific 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 selec tion 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 submitte d information (MRID 49299201) that corrects an application 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

A RTF submission did not alter the selection of 25% as the reasonable, high

- end default value.

Since there was no dermal POD selected for rimsulfuron, an occupational post

- application assessment is not required at this time. Therefore, no additional DFR d ata are required and the 40CFR DFR data requirement is waived.

Turf Transferable Residue (TTR): In accordance with 40CFR158, TTR data are required for all occupational (e.g., sod farms, golf courses, parks, and recreational areas) or residential turf use s that could result in post

- application exposure to turf. In the absence of chemical

- specific TTR data,

EPA uses default values. The 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment includes an analysis of all TTR data, av ailable at the time, which resulted in the selection of revised liquid and granular default values for the fraction of the application rate available for transfer after a turf application (F AR 

### ). These values are based on an analysis of 59 TTR studies performed with the Modified California Roller Method (36 studies using liquids, 11 studies using wettable powders/water dispersible granules, and 12 studies using granules). The liquid results (N=131 ) indicate a range of F AR 

### values from 0.0005% to 6.1% and the granular results (N=37) indicate a range of 0.00064% to 0.69%. In both the liquid and granular data, a large range of transferability is observed and this variability can potentially be attribu table 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 TTR data for a single chemical

. HED selected 1% and 0.2% as high

- end default values for liquid and granular products, respectively. Although TTR data are not available for rimsulfuron, post

- application incidental oral exposure i s not expected from the registered uses of rimsulfuron, and a quantitative dermal occupational or residential post

application exposure assessment was not conducted due to the lack of toxicity via the dermal route of exposure to rimsulfuron. In this insta nce, 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 turf transferrable residues for rimsulfuron.

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 34 of 36 Appendix F . Sulfonylure a Pesticide Class Dermal Toxicity Data

Table F .1. Structure

- Activity Relationship (SAR) Data for Sulfonylureas Technical Formulations

with Available Experimental or Estimated Dermal Absorption Factors (DAF)

Chemical MW Log Kow 1 DAF DAF Basis/Dermal Penetration

Bensulfuron

- methyl 410.4 0.79 4.7% Unpublished in vivo rat study not submitted to EPA (DuPont HLR 120

- 90 2 ).

Chlorimuron

- ethyl 414.8 2.50 4.8% Dermal NOAEL / oral LOAEL extrapolation

. 3

Flazasulfuron 407.3 1.08 20% Estimated maximum per SAR analysis (Log Kp =

- 4.46)

. The closest SAR analog is tribenuron

- methyl (Log Kp =

- 4.51, DAF = 17.7%).

Iododsulfuron

- methyl

sodium 529.2

- 0.70 11% 1

- 6% per in vivo rat study; however 11% used because data indicates absorption continues after

exposure.

Mesosulfuron

- methyl 503.6

- 0.48 An unacceptable/guideline rat in vivo study indicates
11.9

- 26.3%. European document indicates 9% (SANCO/1 0298/2003

- final 2 ).

Nicosulfuron 410.4

- 1.74 0.021

- 0.23% Unpublished in vitro human studies not submitted to EPA (DuPont 21540 and 25519 2 ).

Oxasulfuron 406.4

- 0.81 1% Unpublished in vitro rat and human, and in vivo rat studies not submitted to EPA (EC
SANC0/4323/2002 2 ).

Primisulfuron 468.3 1.15 (pH 5.0) 30% Dermal NOAEL / oral LOAEL extrapolation

. 3

Rimsulfuron 431.4

- 1.46 20% Estimated maximum per SAR analysis (Log Kp =

- 6.41) . The closest SAR analog is iodosulfuron (Kow

=

- 6.24, DAF = 11%). 0.18

- 0.4% per unpublished in

vitro human skin not submitted to EPA (DuPont 24335, 25519 and 24600 2 ).

Tribenuron

- methyl 395.4 0.78 17.7% Per in vivo rat study

. Trifloxysulfuron

sodium 459.3

- 0.42 30% Dermal NOAEL / oral LOAEL extrapolation 3

Tritosulfuron 445.3 0.62 1% Unpublished in vitro rat and human, and in vivo rat studies not submitted to EPA (EC SANC0/1256/08

- rev.1 2 ).

1 Log Kow measured at pH=7 unless otherwise indicated.

2 Concentrate chemical data excerpted in a DuPont submission, MRID 48904001. That document also has some dilute formulation DAFs, which were not considered here.

3 Calculated by dividing the dermal study NOAEL (when no LOAEL was observed) by a subchronic or al LOAEL. Because no dermal toxicity was observed, this will lead to an artificially high DAF.

Kp = skin permeation coefficient ; calculated using the CDC/NIOSH Finite Dose Skin Permeation Calculator at http://www.cdc.gov/niosh/topics/skin/finiteskinpermcal c.html

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 35 of 36 Table F .2. Results of 21/28

- Day Dermal Toxicity Studies ( OCSPP 870.3200 ) for

Sulfo nylureas Technical Formulations.

Chemical Species LOAEL NOAEL Reference (MRID)

Chlorimuron

- Ethyl Rabbit Not observed ≥ 1000 48646201

Foramsulfuron Rat Not observed ≥ 1000 45109608

Flazasulfuron Rabbit Not observed ≥ 1000 46220922

Halosulfuron

- methyl Rat Not observed ≥ 1000 42661417

Imazosulfuron Rat Not observed ≥ 1000 47305236

Metsulfuron

- methyl Rabbit 500 (dermatitis and diarrhea) 125 40357803, 41247801

Orthosulfamuron Rat Not observed ≥ 1000 46578911

Oxasulfuron Rat Not observed ≥ 1000 43414638

Primisulfuron Rabbit Not observed ≥ 1000 41337601, 41135302

Prosulfuron Rabbit Not observed ≥ 1000 42685235

Sulfometuron

- methyl Rabbit Not observed ≥ 2000 00126714

Sulfosulfuron Rat Not observed ≥ 1000 44295752

Triasulfuron Rabbit 10 (dyspnea and ruffled fur) Not observed 41585801

Trifloxysulfuron

- sodium Rat Not observed ≥ 1000 45372004

Trisulfuron

- methyl Rabbit Not observed ≥ 1000 42991409



### Table F.3. Sulfo nylureas with Waived 21/28

- Day Dermal Toxicity Studies ( OCSPP

870.3200 ) Based on Weight of Evidence (WOE) Analysis.

Chemical Reference

(TXR#, Date) WOE Conclusion

Bensulfuron

methyl 0056721,

8/26/13 This approach considered all of the available hazard and exposure information,

particularly that: (1) the low acute dermal toxicity (LD50 is > 2000mg/kg; Toxicity Category III) and 2) The use of an oral POD based on the most sensitive endpoint (liver toxicity) observed in the most sensitive species (dog) after long

- term exposure (1

- year) with a high dermal absorption (75

- 100%) results in acceptable MOEs (>120) with 75% dermal absorption, or MOEs that are close to the level of concern (MOE = 93) with 100% dermal absorption. A longer term study is used to assess short and intermediate term exposure scenarios with high dermal absorption. Therefore, there is high confidence that
the Agency is not underestimating risks in the absence of this study.

Chlorsulfuron 0056439,

2/8/13 This appr oach considered all of the available hazard and exposure information

for chlorsulfuron, including: (1) the low acute dermal toxicity (Toxicity Category III) of chlorsulfuron; (2) the use of an oral POD and assumption of 100% dermal absorption for assessing dermal exposure that results in MOEs greater than 1,100 for risk via the dermal route from occupational exposure; and (3) results of dermal toxicity and dermal absorption studies from other

### Rimsulfuron Human Health Risk Assessment DP No. D 425703

Page 36 of 36 Table F.3. Sulfo nylureas with Waived 21/28

- Day Dermal Toxicity Studies ( OCSPP

870.3200 ) Based on Weight of Evidence (WOE) Analysis.

Chemical Reference

(TXR#, Date) WOE Conclusion

members of this class that support low absorption and low dermal hazard.

Mesosulfuron

methyl 0056562,

2/21/13 This approach considered all of the available hazard and exposure information,

particularly that: (1) the low acute toxicity of mesosulfuron

- methyl (Toxicity Category IV); (2) relatively low dermal absorption (14%); and (3) the use of an oral POD assuming 100% dermal absorption factor resulted in MOEs (>7,300) that are greater than the Agency's LOC.

Nicosulfuron 0050011,

8/2/12 This approach considered the following factors: 1) the relatively low dermal

absorp tion rate (2

- 3%); 2) that there are no risk estimates of concern for any scenario from using the oral PODs (i.e., MOEs are greater than 1000); and 3)
data from structurally related compounds that indicated that there is no evidence that dermal toxicity is a concern for nicosulfuron. When taken together, these lines of evidence (i.e., use pattern, labels require PPE, MOE risk estimates are not of concern without PPE, toxicity considerations) support the conclusion that a dermal toxicity study is not needed a t this time.

Rimsulfuron 0050008,

4/26/12 This approach considered all of the available hazard and exposure information,

particularly that: 1) the available rimsulfuron structural analog data indicate that in the majority of cases, a 21

- or 28

- day dermal toxicity study will result
in NOAELs ≥ 1000 mg/kg/day for sulfonylurea herbicides; and 2) the available
rimsulfuron and sulfuron analog in vitro data indicate that dermal penetration of human skin is generally low.

Thifensulfuron

methyl 0054114,

3/7/12 The HASPOC considered the following factors: 1) discussed the potential for

differences in toxicity between the dermal and oral routes of exposure based on pharmacokinetic differences (i.e., dermal exposure by passes the liver); 2) the high dermal absorption (100%) rate assumed in the risk assessment; 3) the PODs used for dermal risk assessments could have been higher and resulted in higher MOEs due to more than 25

- fold difference between the NOAEL and
the LOAEL (i.e. because of the wide spacing between the do ses, the true NOAEL is likely to higher); and 4) there are no risks of concern for any scenario from using the oral PODs (i.e., MO Es greater than 320). When taken together, these lines of evidence (i.e., use pattern, labels require PPE, MOE
risk estimates are not of concern with PPE, toxicity considerations) support the
conclusion that a dermal toxicity study is not needed at this time.

Tribenuron

methyl 0056650,

6/17/13 This approach considered all of the available hazard and exposure information,

includ ing: (1) the low acute toxicity of tribenuron methyl (Toxicity Category III); (2) that the use of an oral POD and the 18% dermal absorption factor resulted in MOEs ≥510; and (3) the POD use for assessing risk from
intermediate term exposure could be higher due to dose spacing (i.e., there is a large gap between the NOAEL and the LOAEL), which would have resulted in higher MOEs.